Burden of gastrointestinal cancers among working-age population over past thirty years in China

doi:10.4251/wjgo.v16.i9.3955

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World J Gastrointest Oncol. Sep 15, 2024; 16(9): 3955-3979
Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.3955

Burden of gastrointestinal cancers among working-age population over past thirty years in China

Yu Dong, Zhuan-Zhuan Fan, Wen-Ting Li, Jian Kang, Yan Zhang, Yue Guan, Hui-Qing Xu, Jie Yuan, Fei Xu

Yu Dong, Yan Zhang, Yue Guan, Jie Yuan, Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China

Zhuan-Zhuan Fan, Wen-Ting Li, Fei Xu, Department of Primary Healthcare Management, Nanjing Municipal Center for Disease Control and Prevention, Nanjing 210003, Jiangsu Province, China

Jian Kang, Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China

Hui-Qing Xu, Fei Xu, Department of Epidemiology, Nanjing Medical University School of Public Health, Nanjing 211116, Jiangsu Province, China

ORCID number: Fei Xu (0000-0003-1785-3635).

Co-first authors: Yu Dong and Zhuan-Zhuan Fan.

Co-corresponding authors: Jie Yuan and Fei Xu.

Author contributions: Yuan J and Xu F conceived, designed and supervised the study, they are the co-corresponding authors of this manuscript; Dong Y and Fan ZZ were responsible for data acquisition, and they contributed equally to this manuscript; Fan ZZ was responsible for data analysis; Dong Y, Fan ZZ, Li WT, Kang J, Zhang Y, Guan Y, Xu HQ, Yuan J, and Xu F wrote and critically reviewed the manuscript. All authors approved the final version for submission and was also responsible for all aspects of the work presented in this manuscript.

Supported by Nanjing Medical Science and Technique Development Foundation, No. YKK22195; and the National Natural Science Foundation of China, No. 52078254.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Fei Xu, PhD, Professor, Department of Primary Healthcare Management, Nanjing Municipal Center for Disease Control and Prevention, No. 3 Zizhulin, Nanjing 210003, Jiangsu Province, China. frankxufei@163.com

Received: June 27, 2024
Revised: July 15, 2024
Accepted: August 7, 2024
Published online: September 15, 2024
Processing time: 73 Days and 22.5 Hours

Abstract

BACKGROUND

Although gastrointestinal (GI) cancers have been becoming a great public health concern in China, there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population.

AIM

To assess the burden of GI cancers and to examine the overall, age- and gender-specific trends among the working-age population in China from 1990 to 2019.

METHODS

Data were extracted from the Global Burden of Disease Study 2019. The burden of GI cancers was indicated by incidence, mortality, disability-adjusted life-years (DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALYs rate. Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models.

RESULTS

For overall GI cancers, a declining trend was observed in the ASIR, age-standardized mortality rate, and age-standardized DALYs rate, with reductions of 0.74%, 2.23%, and 2.22%, respectively, from 1999 to 2019 in the Chinese working-age population. However, an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019. The number of either incident cases, mortality cases, and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal, gallbladder, biliary tract, pancreatic, and stomach cancer among older subjects. Moreover, sex disparity in the GI cancers burden was also examined over 30 years.

CONCLUSION

The total burden of GI cancers remained heavy among the working-age population in China, although declining trends were observed from 1999 to 2019. Disparities in the GI cancers burden existed between sexes, age groups, and cancer types. Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals, considering the age, sex, and cancer type disparities in China.

Key Words: Gastrointestinal cancer; Working-age population; Disease burden; Disability-adjusted life-years; Chinese

Core Tip: This is the first study that systematically assessed total burden of gastrointestinal (GI) cancers among the working-age population in China. It was observed that GI cancers burden remained much heavy among working-age population, although declining trends in burden of GI cancers were examined from 1990 to 2019 in China. Moreover, substantial disparities in burden of GI cancers existed between genders, age-groups and cancer types. This study has important public health implications that precision prevention policies and strategies are needed for tackling GI cancers among working-age people with consideration of age-, gender- and type-specific effective and accessible approaches in China.

Citation: Dong Y, Fan ZZ, Li WT, Kang J, Zhang Y, Guan Y, Xu HQ, Yuan J, Xu F. Burden of gastrointestinal cancers among working-age population over past thirty years in China. World J Gastrointest Oncol 2024; 16(9): 3955-3979
URL: https://www.wjgnet.com/1948-5204/full/v16/i9/3955.htm
DOI: https://dx.doi.org/10.4251/wjgo.v16.i9.3955

INTRODUCTION

Gastrointestinal (GI) cancers are malignant conditions of the GI tract or the accessory organs involved in digestion, including esophagus, stomach, biliary system, pancreas, intestine, rectum and anus[1]. Common types of GI cancers include colon and rectal cancer, esophageal cancer, liver cancer, stomach cancer, pancreatic cancer, and gallbladder and biliary tract cancer[1,2]. In 2020, there were approximately 5 million newly-identified GI cancer cases and 3.5 million deaths worldwide[3]. China, the most populous country, accounted for 18.2% of the overall global population[4] but reported disproportionately as high as 37.4% of the total GI cancer cases diagnosed in 2020 worldwide[3]. Meanwhile, of all cancer cases recorded in China in 2020, 38.8% were GI cancers[5]. Thus, the disease burden caused by GI cancers is much heavier in China, and should be assessed systemically and periodically for informing precision prevention of GI cancers.

GI cancers usually have a poor prognosis. Patients also have a lowed quality of life and, in particular, reduced labor capacity for those at working age[6]. Working-age people, or the workforce, typically refer to those aged 15-64 years worldwide[7]. In China, individuals aged 15-64 years are officially defined as the workforce by the China National Bureau of Statistics[8]. In 2020, 68.7% of residents in China were aged 15-64[4]. For the workforce, labor capacity is vital not only for community-level social production and economic development, but also for personal earnings and family livelihood. To date, the disease burden of GI cancers was reported only for the overall population at the global, regional, and country levels[3,9-14]. No study has assessed the GI cancer burden for working-age population, the crucial individuals for society, and families. To fill this gap, we estimated the incidence, mortality, and disability-adjusted life-years (DALYs) of GI cancers to systematically assess the disease burden for the working-age subpopulation in China. Specifically, we investigated the burden of GI cancers and their temporal trends from 1990 to 2019 and then compared the disease burden trends between types of GI cancer, sexes, and age groups over the three decades.

MATERIALS AND METHODS

Data sources and definitions

In this study, all information on GI cancers was obtained from The Global Burden of Disease Study 2019 (GBD 2019) using the GBD results tool (data source: Institute for Health Metrics and Evaluation. Available at: https://vizhub.healthdata.org/gbd-results/. Used with permission. All rights reserved). The methodology, metrics, and statistical strategies of the GBD 2019 study have been detailed elsewhere[15-17]. The GI cancers analyzed in the present study were colorectal, esophageal, gallbladder and biliary tract, liver, pancreatic, and stomach cancers. GI cancers were identified based on the International Classification of Diseases, Tenth Revision codes: Colon and rectal cancer (C18, C19, C20, and C21), esophageal cancer (C15), gallbladder and biliary tract cancer (C23 and C24), liver cancer (C22), pancreatic cancer (C25), and stomach cancer (C16).

Data were extracted from GBD 2019 using such a search strategy, assigning “number and rate” as the metrics, “both, male and female” as the sex, “15 to 64 years and corresponding 5-year bands” as the age, “incidence, deaths, and DALYs” as the measure, “China” as the location, “1990-2019” as the years, and “colon and rectum, esophageal, gallbladder and biliary tract, liver, pancreatic, and stomach cancer” as the causes. All data in the GBD study were publicly available without personal identification; therefore, ethical approval was waived for this study.

Study population and measures

The study participants were working-age people in China, referring to those aged 15-64 years according to the official definition of working-age people by the China National Bureau of Statistics[8]. Working-age individuals diagnosed with any of the six types of GI cancer were subjects with outcome events in this study. Statistical outcome measures included case number and incidence rate, mortality number, mortality rate, DALYs, DALYs rates, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) of GI cancers. The annual percent change (APC) and average annual percent change (AAPC) were calculated to examine trends in the burden of GI cancers over the three decades. Participants were classified by sex and categorized into 10 age-groups with a 5-year interval for the analysis.

Statistical analysis

First, the burden of GI cancers by participant age, sex, and cancer type was assessed using a descriptive analysis approach. The number of cases of incidence and mortality, DALYS, ASIR, ASMR, and ASDR, together with the 95% uncertainty interval (95%UI), were estimated for each GI cancer by sex and age. The sum of the individual burdens caused by colon, rectal, esophageal, gallbladder, biliary tract, liver, pancreatic, and stomach cancers was calculated to determine the total burden of all six GI cancers[18]. The ASIR, ASMR, and ASDR of GI cancers among working-age populations were estimated using the directed method of standardization[17], which is a widely used standardization approach[19].

Second, Joinpoint regression models were introduced to calculate the AAPC and APC for the crude incidence rate (CIR), crude mortality rate (CMR), crude DALYs rate (CDR), ASIR, ASMR, and ASDR to assess temporal trends in the burden of GI cancers from 1990 to 2019 among the working-age population in China. The AAPC/APC value was then used to examine temporal trends in the incidence, mortality, and DALYs of GI cancers, with APC/AAPC > 0 indicating an increasing trend and APC/AAPC < 0 indicating a declining trend[20]. The Joinpoint regression analysis was conducted using the Joinpoint Regression Program software (version 4.9.0.1, Statistical Research and Applications Branch, National Cancer Institute, United States), and all other analyses were performed using R software (version 4.1.3).

RESULTS

Burden of GI cancers among overall working-age population in China in 2019

Table 1 presents the burden of GI cancer among the working-age population of China in 2019. For all kinds of GI cancer analyzed in this study, the total number of reported incidence and death case, separately, was 825870 (95%UI: 667914-1005427) and 473970 (95%UI: 382518-578412), while the overall DALYs was 17083512 (95%UI: 13852170-20783548) among working-age population in 2019 in China. Of the six kinds of GI cancer, the three most common types were colon and rectal cancer (283322 cases, 95%UI: 234698-339847), stomach cancer (258317 cases, 95%UI: 208931-314979), and liver cancer (122607 cases, 95%UI: 97932-151349) according to the number of incidence case. When assessed using DALYs, the top three cancers were stomach cancer (5108526 cases, 95%UI: 4165635-6172708), liver cancer (3735886 cases, 95%UI: 3011992-4586337), and colon and rectal cancer (3527247 cases, 95%UI: 2949667-4194243). Moreover, stomach cancer (144177cases, 95%UI: 117126-174989), liver cancer (99340 cases, 95%UI: 80088-122060), and colon and rectal cancer (92784 cases, 95%UI: 76834-111032) also ranked in the top three among the six types of GI cancer based on the number of cases of mortality.

Table 1 Burden of gastrointestinal cancers among working-age population in China 1990-2019.

Participants	Type of GI cancers	1990		2019		1990		2019		1990		2019
Participants	Type of GI cancers	Incident case (95%UI)	ASIR (95%UI)	Incident case (95%UI)	ASIR (95%UI)	Mortality case (95%UI)	ASMR (95%UI)	Mortality case (95%UI)	ASMR (95%UI)	DALYs (95%UI)	ASDR (95%UI)	DALYs (95%UI)	ASDR
Overall	Colon and rectum cancer	59982 (51662-69155)	9.19 (7.92-10.58)	283322 (234698-339847)	21.82 (18.09-26.14)	39243 (33370-45379)	6.06 (5.15-7.00)	92784 (76834-111032)	7.08 (5.87-8.46)	1551325 (1321613-1795526)	232.54 (198.14-269.02)	3527247 (2949667-4194243)	276.29 (231.34-328.05)
	Esophageal cancer	83601 (52815-101343)	13.5 (8.53-16.36)	100481 (77654-125529)	7.37 (5.70-9.2)	77754 (48830-94098)	12.57 (7.90-15.21)	82457 (64032-103637)	6.04 (4.70-7.59)	2667461 (1669627-3231928)	427.7 (267.89-518.13)	2776889 (2165721-3490970)	204.47 (159.64-257)
	Gallbladder and biliary tract cancer	5783 (4618-9086)	0.91 (0.72-1.44)	13353 (9311-16517)	1.01 (0.70-1.25)	5089 (4037-8055)	0.80 (0.64-1.28)	10839 (7901-13359)	0.81 (0.59-1.00)	186982 (148524-288642)	28.9 (22.97-45.15)	376720 (275756-464927)	28.53 (20.87-35.2)
	Liver cancer	163523 (133423-200151)	25.3 (20.62-30.98)	122607 (97932-151349)	9.47 (7.58-11.68)	151613 (123716-185529)	23.56 (19.21-28.85)	99340 (80088-122060)	7.61 (6.14-9.35)	5934861 (4849189-7246002)	901.79 (736.1-1102.08)	3735886 (3011992-4586337)	293.91 (237.06-360.47)
	Pancreatic cancer	14947 (12533-17462)	2.35 (1.97-2.75)	47790 (39387-57206)	3.59 (2.96-4.29)	13993 (11678-16500)	2.21 (1.85-2.61)	44372 (36537-53335)	3.32 (2.74-3.99)	510853 (425892-603413)	79.26 (66.09-93.55)	1558243 (1283400-1874362)	118.61 (97.75-142.63)
	Stomach cancer	167983 (143406-194818)	26.54 (22.65-30.79)	258317 (208931-314979)	19.6 (15.89-23.86)	147121 (124564-170800)	23.34 (19.76-27.11)	144177 (117126-174989)	10.8 (8.79-13.09)	5346879 (4534010-6202702)	833.88 (706.71-967.6)	5108526 (4165635-6172708)	389.57 (318.39-469.71)
	All GI cancers	495819 (398457-592016)	77.78 (62.42-92.89)	825870 (667914-1005427)	62.86 (50.91-76.42)	434813 (346195-520361)	68.54 (54.5-82.05)	473970 (382518-578412)	35.67 (28.82-43.49)	16198362 (12948854-19368214)	2504.05 (1997.89-2995.53)	17083512 (13852170-20783548)	1311.38 (1065.04-1593.06)
Female	Colon and rectum cancer	26640 (21308-32353)	8.55 (6.85-10.36)	92647 (71959-117263)	14.32 (11.11-18.15)	17436 (13922-21216)	5.64 (4.50-6.85)	30156 (23607-38017)	4.63 (3.62-5.84)	685852 (548140-836447)	215.63 (172.52-262.39)	1131966 (891965-1417160)	178.33 (140.28-223.35)
	Esophageal cancer	21747 (11072-27418)	7.34 (3.73-9.25)	17032 (12295-22055)	2.54 (1.83-3.29)	19571 (10003-24688)	6.62 (3.38-8.35)	11179 (8317-14480)	1.66 (1.23-2.15)	651951 (335203-823783)	218.91 (112.25-276.38)	367832 (274504-475564)	54.92 (40.95-71.05)
	Gallbladder and biliary tract cancer	2871 (2122-4710)	0.95 (0.70-1.56)	5808 (3487-7731)	0.88 (0.53-1.17)	2536 (1865-4288)	0.84 (0.62-1.43)	4662 (2873-6177)	0.70 (0.43-0.92)	91445 (67071-151766)	29.79 (21.89-49.84)	158513 (98069-210224)	23.94 (14.82-31.8)
	Liver cancer	37701 (28919-48516)	12.26 (9.42-15.74)	21942 (16829-28109)	3.38 (2.59-4.34)	35035 (26803-45164)	11.45 (8.78-14.75)	18356 (14060-23353)	2.80 (2.14-3.56)	1335631 (1016929-1723984)	426.56 (325.5-549.72)	657433 (502843-837012)	102.83 (78.53-131.04)
	Pancreatic cancer	5516 (4430-6670)	1.82 (1.47-2.2)	16130 (12563-20380)	2.42 (1.88-3.05)	5163 (4117-6293)	1.71 (1.37-2.09)	14952 (11725-18767)	2.23 (1.75-2.8)	186134 (148305-227692)	60.64 (48.37-74.03)	510739 (400674-641427)	77.35 (60.62-97.16)
	Stomach cancer	52953 (42468-64157)	17.24 (13.85-20.86)	60640 (47197-76580)	9.45 (7.35-11.94)	46685 (37528-56368)	15.29 (12.31-18.44)	35994 (28087-45498)	5.51 (4.30-6.97)	1750712 (1404045-2120016)	560.77 (450.37-677.79)	1296908 (1014007-1637485)	203.67 (159.06-257.22)
	All GI cancers	147429 (110318-183823)	48.16 (36.01-59.98)	214198 (164329-272118)	32.99 (25.30-41.93)	126426 (94239-158017)	41.56 (30.95-51.89)	115299 (88669-146292)	17.53 (13.47-22.25)	4701725 (3519694-5883688)	1512.29 (1130.89-1890.15)	4123391 (3182062-5218871)	641.05 (494.27-811.61)
Male	Colon and rectum cancer	33342 (26831-40539)	9.77 (7.85-11.88)	190675 (146570-243048)	29.16 (22.47-37.08)	21807 (17394-26522)	6.44 (5.13-7.84)	62628 (48259-79637)	9.49 (7.33-12.03)	865472 (693050-1050247)	248.07 (198.45-301.18)	2395280 (1867748-3008970)	371.97 (290.90-465.92)
	Esophageal cancer	61853 (39574-77609)	19.11 (12.25-23.98)	83449 (62294-107873)	12.13 (9.06-15.67)	58183 (36214-72589)	18.00 (11.22-22.45)	71278 (53690-92312)	10.36 (7.81-13.42)	2015511 (1247431-2515787)	617.82 (382.93-771.08)	2409057 (1823793-3117767)	351.64 (266.55-455.06)
	Gallbladder and biliary tract cancer	2912 (2131-4838)	0.87 (0.64-1.46)	7545 (4975-9893)	1.13 (0.75-1.49)	2552 (1903-4239)	0.77 (0.57-1.29)	6176 (4255-8150)	0.92 (0.63-1.21)	95538 (71137-154166)	28.07 (20.94-45.93)	218207 (150468-287046)	33.00 (22.74-43.35)
	Liver cancer	125821 (98064- 158708)	37.17 (28.94-46.91)	100665 (77103-129041)	15.43 (11.84-19.74)	116577 (91020-147041)	34.58 (26.98-43.66)	80984 (61960- 103400)	12.32 (9.44-15.71)	4599231 (3600710-5786258)	1334.42 (1043.34-1680.88)	3078453 (2361884-3917311)	480.20 (368.89-609.84)
	Pancreatic cancer	9431 (7333-11700)	2.84 (2.21-3.52)	31661 (24192-40467)	4.73 (3.62-6.04)	8830 (6903-11074)	2.67 (2.09-3.35)	29421 (22464-37573)	4.39 (3.36-5.60)	324719 (253742-407077)	96.23 (75.17-120.71)	1047505 (801913-1335710)	158.94 (121.96-202.39)
	Stomach cancer	115030 (92556-139124)	35.04 (28.18-42.4)	197678 (152032-253149)	29.58 (22.80-37.79)	100436 (80334-121207)	30.71 (24.55-37.07)	108183 (82801-137765)	16.01 (12.28-20.36)	3596166 (2885420-4333655)	1082.86 (868.18-1305.91)	3811618 (2935329-4823650)	572.22 (441.97-722.54)
	All GI cancers	348390 (266489-432518)	104.8 (80.06-130.16)	611672 (467167-783471)	92.16 (70.54-117.81)	308387 (233768-382672)	93.16 (70.53-115.66)	358671 (273430-458837)	53.49 (40.85-68.33)	11496637 (8751490-14247189)	3407.47 (2589-4225.69)	12960121 (9941135-16490455)	1967.97 (1513.01-2499.1)

GI: Gastrointestinal; UI: Uncertainty interval; ASIR: Age-standardized mortality rate; ASMR: Age-standardized mortality rate; DALYs: Disability-adjusted life-years; ASDR: Age-standardized disability-adjusted life-years rate.

The ASIR, ASMR and ASDR were 62.86 (95%UI: 50.91-76.42), 35.67 (95%UI: 28.82-43.49) and 1311.38 (95%UI: 1065.04-1593.06), respectively, among overall participants in 2019 in China. Additionally, the highest ASIR (21.82, 95%UI: 18.09-26.14) was determined for colon and rectal cancer, whereas the highest ASMR (10.8, 95%UI: 8.79-13.09) and ASDR (389.57, 95%UI: 318.39-469.71) were recorded for stomach cancer among all types of GI cancer among working-age people in China.

Trends in the burden of GI cancers among overall working-age population from 1990 to 2019 in China

Table 2 shows the temporal trends in the burden of GI cancers among the working-age population of China from 1990 to 2019. For overall GI cancers, a sustained downward trend was observed in ASIR, ASMR, and ASDR, with reductions of 0.74%, 2.23%, and 2.22%, respectively, over the three decades. However, an unfavorable upward trend in ASIR (APC = 1.64%, P < 0.001) was observed for overall GI cancers in the recent period of 2016-2019 among participants.

Table 2 Temporal trends in burden of gastrointestinal cancers among working-age population in China 1990-2019.

Measure of burden	Gender	Type of GI cancers	AAPC	P value	Trend 1			Trend 2			Trend 3			Trend 4			Trend 5			Trend 6
Measure of burden	Gender	Type of GI cancers	AAPC	P value	Years	APC	P value	Years	APC	P value	Years	APC	P value	Years	APC	P value	Years	APC	P value	Years	APC	P value
ASIR	Overall	Colon and rectum cancer	3.00	< 0.001	1990-1996	-0.02	0.852	1996-2000	2.99	< 0.001	2000-2004	7.64	< 0.001	2014-2010	4.80	< 0.001	2010-2016	1.00	< 0.001	2016-2019	3.57	< 0.001
		Esophageal cancer	-2.08	< 0.001	1990-1997	-1.29	< 0.001	1997-2004	2.40	< 0.001	2004-2007	-4.68	< 0.001	2007-2014	-6.37	< 0.001	2014-2017	-3.22	< 0.001	2017-2019	0.83	0.129
		Gallbladder and biliary tract cancer	0.33	0.137	1990-1995	-2.52	< 0.001	1995-1998	-1.275	0.236	1998-2001	4.62	0.001	2001-2014	7.719	< 0.001	2014-2007	1.45	0.186	2007-2019	-1.17	< 0.001
		Liver cancer	-3.35	< 0.001	1990-1994	2.2	< 0.001	1994-1998	-2.12	< 0.001	1998-2001	-6.75	< 0.001	2001-2005	-17.96	< 0.001	2005-2010	-2.16	< 0.001	2010-2019	1.36	< 0.001
		Pancreatic cancer	1.43	< 0.001	1990-1995	-0.73	< 0.001	1995-1998	1.48	0.06	1998-2004	3.48	< 0.001	2004-2011	1.78	< 0.001	2011-2016	-0.15	0.512	2016-2019	2.85	< 0.001
		Stomach cancer	-1.05	< 0.001	1990-1996	-2.50	< 0.001	1996-1999	-0.03	0.967	1999-2004	4.00	< 0.001	2004-2010	-2.44	< 0.001	2010-2016	-3.34	< 0.001	2016-2019	0.11	0.756
		All GI cancers	-0.74	< 0.001	1990-1993	-0.20	0.558	1993-1998	-1.11	< 0.001	1998-2002	-0.15	0.658	2002-2016	-1.39	< 0.001	2016-2019	1.61	< 0.001	N/A	N/A	N/A
	Female	Colon and rectum cancer	1.77	< 0.001	1990-1996	-0.31	0.037	1996-2001	1.89	< 0.001	2001-2004	4.72	< 0.001	2014-2010	3.03	< 0.001	2010-2016	0.16	0.399	2016-2019	3.67	< 0.001
		Esophageal cancer	-3.63	< 0.001	1990-1998	-1.36	< 0.001	1998-2004	2.40	< 0.001	2004-2008	-8.67	< 0.001	2008-2013	-10.57	< 0.001	2013-2016	-6.15	< 0.001	2016-2019	0.17	0.81
		Gallbladder and biliary tract cancer	-0.26	0.115	1990-1998	-2.61	< 0.001	1998-2001	4.169	< 0.001	2001-2004	7.40	< 0.001	2004-2007	0.13	0.888	2007-2014	-2.31	< 0.001	2014-2019	-0.81	0.001
		Liver cancer	-4.40	< 0.001	1990-1995	0.06	0.826	1995-1998	-3.90	0.006	1998-2001	-7.45	< 0.001	2001-2005	-16.59	< 0.001	2005-2011	-3.56	< 0.001	2011-2019	-0.17	0.223
		Pancreatic cancer	0.96	< 0.001	1990-1995	-0.05	0.811	1995-1998	0.60	0.515	1998-2002	2.27	< 0.001	2002-2007	1.23	0.001	2007-2016	-0.01	0.892	2016-2019	3.83	< 0.001
		Stomach cancer	-2.04	< 0.001	1990-1998	-2.44	< 0.001	1998-2004	1.35	< 0.001	2004-2015	-4.21	< 0.001	2015-2019	-0.19	0.399	N/A	N/A	N/A	N/A	N/A	N/A
		All GI cancers	-1.29	< 0.001	1990-1993	-0.89	0.009	1993-1998	-1.68	< 0.001	1998-2003	-0.40	0.049	2003-2013	-2.54	< 0.001	2013-2016	-1.51	0.023	2016-2019	1.91	< 0.001
	Male	Colon and rectum cancer	3.82	< 0.001	1990-1996	0.17	0.183	1996-2000	4.04	< 0.001	2000-2004	10.27	< 0.001	2014-2011	5.39	< 0.001	2011-2016	0.91	0.002	2016-2019	3.86	< 0.001
		Esophageal cancer	-1.56	< 0.001	1990-1997	-1.12	< 0.001	1997-2004	2.67	< 0.001	2004-2007	-3.35	< 0.001	2007-2014	-5.28	< 0.001	2017-2017	-3.13	< 0.001	2017-2019	0.8	0.211
		Gallbladder and biliary tract cancer	0.90	< 0.001	1990-1995	-2.23	< 0.001	1995-1998	-0.42	0.596	1998-2001	5.48	< 0.001	2001-2005	7.18	< 0.001	2005-2010	0.64	0.021	2010-2019	-0.93	< 0.001
		Liver cancer	-2.99	< 0.001	1990-1994	2.71	< 0.001	1994-1998	-1.76	< 0.001	1998-2001	-6.38	< 0.001	2001-2005	-18.26	< 0.001	2005-2010	-1.55	< 0.001	2010-2019	1.85	< 0.001
		Pancreatic cancer	1.74	< 0.001	1990-1995	-1.19	< 0.001	1995-1999	2.43	< 0.001	1999-2004	4.65	< 0.001	2004-2012	2.32	< 0.001	2011-2016	-0.53	0.23	2016-2019	2.52	< 0.001
		Stomach cancer	-0.60	< 0.001	1990-1996	-2.39	< 0.001	1996-1999	0.43	0.587	1999-2004	5.16	< 0.001	2004-2010	-1.66	< 0.001	2010-2016	-3.12	< 0.001	2016-2019	-0.06	0.884
		All GI cancers	-0.45	< 0.001	1990-1992	0.51	0.45	1992-1998	-0.78	< 0.001	1998-2001	0.12	0.856	2001-2012	-0.84	< 0.001	2012-2016	-1.25	0.002	2016-2019	1.56	< 0.001
ASMR	Overall	Colon and rectum cancer	0.52	< 0.001	1990-1997	-1.22	< 0.001	1997-2000	1.71	0.009	2000-2004	4.69	< 0.001	2004-2011	0.64	< 0.001	2011-2016	-1.56	< 0.001	2016-2019	1.19	0.001
		Esophageal cancer	-2.49	< 0.001	1990-1998	-1.26	< 0.001	1998-2004	2.43	< 0.001	2004-2007	-5.55	< 0.001	2007-2014	-6.80	< 0.001	2014-2017	-3.63	< 0.001	2017-2019	0.02	0.97
		Gallbladder and biliary tract cancer	-0.01	0.951	1990-1995	-2.73	< 0.001	1995-1998	-1.60	0.136	1998-2001	4.44	0.001	2001-2014	7.45	< 0.001	2004-2007	0.93	0.379	2007-2019	-1.57	< 0.001
		Liver cancer	-3.80	< 0.001	1990-1996	1.11	< 0.001	1996-2000	-4.43	< 0.001	2000-2004	-18.45	< 0.001	2004-2007	-5.81	0.001	2007-2012	-2.34	< 0.001	2012-2019	1.51	< 0.001
		Pancreatic cancer	1.38	< 0.001	1990-1995	-0.77	< 0.001	1995-1998	1.41	0.07	1998-2004	3.49	< 0.001	2004-2011	1.71	< 0.001	2011-2016	-0.23	0.325	2016-2019	2.76	< 0.001
		Stomach cancer	-2.66	< 0.001	1990-1997	-3.04		1997-2000	0.72	0.318	2000-2004	2.9		2004-2015	-5.16	< 0.001	2015-2019	-2.91		N/A	N/A	N/A
		All GI cancers	-2.23	< 0.001	1990-1993	-0.63	0.01	1993-2000	-1.46	< 0.001	2000-2004	-2.79	< 0.001	2004-2014	-3.66	< 0.001	2014-2017	-1.48	0.003	2017-2019	-0.12	0.77
	Female	Colon and rectum cancer	-0.72	< 0.001	1990-1997	-1.7	< 0.001	1997-2001	0.13	0.712	2001-2004	1.67	0.037	2004-2011	-0.98	< 0.001	2011-2015	-2.49	< 0.001	2015-2019	0.61	0.018
		Esophageal cancer	-4.72	< 0.001	1990-1998	-2.23	< 0.001	1998-2004	1.53	0.001	2004-2007	-9.83	< 0.001	2007-2013	-11.69	< 0.001	2013-2016	-7	0.001	2016-2019	-1.32	0.122
		Gallbladder and biliary tract cancer	-0.65	< 0.001	1990-1998	-3.00	< 0.001	1998-2001	3.93	0.001	2001-2004	7.26	< 0.001	2004-2007	-0.55	0.545	2007-2014	-2.77	< 0.001	2014-2019	-1.17	< 0.001
		Liver cancer	-4.74	< 0.001	1990-1996	-0.31	0.087	1996-2000	-5.65	< 0.001	2000-2004	-16.99	< 0.001	2004-2007	-6.39	< 0.001	2007-2012	-4.25	< 0.001	2012-2019	0.04	0.771
		Pancreatic cancer	0.91	< 0.001	1990-1997	0.01	0.962	1997-2006	1.81	< 0.001	2006-2016	-0.09	0.381	2016-2019	3.75	< 0.001	N/A	N/A	N/A	N/A	N/A	N/A
		Stomach cancer	-3.48	< 0.001	1990-1998	-3.13	< 0.001	1998-2004	0.39	0.011	2004-2014	-6.42	< 0.001	2014-2019	-2.58	< 0.001	N/A	N/A	N/A	N/A	N/A	N/A
		All GI cancers	-2.93	< 0.001	1990-1993	-1.39	0.001	1993-2004	-2.36	< 0.001	2004-2013	-5.21	< 0.001	2013-2016	-2.31	0.003	2016-2019	-0.25	0.455	N/A	N/A	N/A
	Male	Colon and rectum cancer	1.32	< 0.001	1990-1996	-0.99	< 0.001	1996-1999	1.23	0.036	1999-2004	6.53	< 0.001	2004-2011	1.66	< 0.001	2011-2016	-1.25	< 0.001	2016-2019	1.15	0.001
		Esophageal cancer	-1.89	< 0.001	1990-1997	-1.23	< 0.001	1997-2004	2.42	< 0.001	2004-2007	-3.86	< 0.001	2007-2014	-5.73	< 0.001	2014-2017	-3.49	< 0.001	2017-2019	0.14	0.819
		Gallbladder and biliary tract cancer	0.61	< 0.001	1990-1995	-2.31	< 0.001	1995-1998	-0.60	0.449	1998-2001	5.31	< 0.001	2001-2005	6.8	< 0.001	2005-2010	0.25	0.325	2010-2019	-1.33	< 0.001
		Liver cancer	-3.47	< 0.001	1990-1996	1.66	< 0.001	1996-2000	-4.57	< 0.001	2000-2005	-17.1	< 0.001	2005-2012	-1.84	< 0.001	2012-2019	1.92	< 0.001	N/A	N/A	N/A
		Pancreatic cancer	1.69	< 0.001	1990-1995	-1.21	< 0.001	1995-1999	2.41	< 0.001	1999-2004	4.63	< 0.001	2004-2012	2.25	< 0.001	2012-2016	-0.61	0.164	2016-2019	2.43	< 0.001
		Stomach cancer	-2.26	< 0.001	1990-1996	-3.02	< 0.001	1996-1999	-0.43	0.652	1999-2004	3.6	< 0.001	2004-2008	-4.01	< 0.001	2008-2015	-4.97	< 0.001	2015-2019	-3.02	< 0.001
		All GI cancers	-1.92	< 0.001	1990-1993	-0.34	0.436	1993-2000	-1.01	< 0.001	2000-2015	-2.96	< 0.001	2015-2019	-0.75	0.011	N/A	N/A	N/A	N/A	N/A	N/A
ASDR	Overall	Colon and rectum cancer	0.59	< 0.001	1990-1997	-0.99	< 0.001	1997-2000	1.71	0.002	2000-2004	4.09	< 0.001	2004-2011	0.67	< 0.001	2011-2016	-1.29	< 0.001	2016-2019	1.55	< 0.001
		Esophageal cancer	-2.53	< 0.001	1990-1997	-1.43	< 0.001	1997-2004	1.99	< 0.001	2004-2007	-5.58	< 0.001	2007-2014	-6.98	< 0.001	2014-2017	-3.48	< 0.001	2017-2019	0.21	0.71
		Gallbladder and biliary tract cancer	-0.02	0.895	1990-1998	-2.23	< 0.001	1998-2001	4.58	< 0.001	2001-2004	6.58	< 0.001	2004-2007	0.98	0.167	2007-2015	-1.74	< 0.001	2015-2019	-0.97	< 0.001
		Liver cancer	-3.77	< 0.001	1990-1996	1.17	< 0.001	1996-2000	-4.55	< 0.001	2000-2004	-18.41	< 0.001	2004-2007	-5.82	0.001	2007-2012	-2.31	< 0.001	2012-2019	1.6	< 0.001
		Pancreatic cancer	1.37	< 0.001	1990-1995	-0.72	0.001	1995-1998	1.67	0.044	1998-2004	3.27	< 0.001	2004-2011	1.63	< 0.001	2011-2016	-0.17	0.477	2016-2019	2.88	< 0.001
		Stomach cancer	-2.61	< 0.001	1990-1997	-2.89	< 0.001	1997-2000	0.89	0.15	2000-2004	2.51	< 0.001	2004-2015	-5.17	< 0.001	2015-2019	-2.56	< 0.001	N/A	N/A	N/A
		All GI cancers	-2.22	< 0.001	1990-1994	-0.66	0.002	1994-2000	-1.46	< 0.001	2000-2005	-3.33	< 0.001	2005-2013	-3.70	< 0.001	2013-2016	-1.97	0.002	2016-2019	-0.17	0.535
	Female	Colon and rectum cancer	-0.68	< 0.001	1990-1996	-1.22	< 0.001	1996-2005	-0.08	0.108	2005-2011	-0.98	< 0.001	2011-2015	-2.21	< 0.001	2015-2019	0.78	< 0.001	N/A	N/A	N/A
		Esophageal cancer	-4.70	< 0.001	1990-1998	-1.80	< 0.001	1998-2004	1.19	0.001	2004-2007	-10.13	< 0.001	2007-2013	-11.76	< 0.001	2013-2016	-6.92	< 0.001	2016-2019	-1.2	0.081
		Gallbladder and biliary tract cancer	-0.73	< 0.001	1990-1998	-2.59	< 0.001	1998-2001	3.49	< 0.001	2001-2004	5.87	< 0.001	2004-2007	-0.74	0.308	2007-2014	-2.8	< 0.001	2014-2019	-1.12	< 0.001
		Liver cancer	-4.77	< 0.001	1990-1996	0.19	0.214	1996-2000	-5.50	< 0.001	2000-2004	-17.77	< 0.001	2004-2007	-6.54	< 0.001	2007-2012	-4.27	< 0.001	2012-2019	0.03	0.83
		Pancreatic cancer	0.85	< 0.001	1990-1997	0.27	0.042	1997-2001	1.91	0.001	2001-2007	0.84	0.001	2007-2016	-0.11	0.28	2016-2019	3.73	< 0.001	N/A	N/A	N/A
		Stomach cancer	-3.44	< 0.001	1990-1997	-2.79	< 0.001	1997-2004	-0.59	< 0.001	2004-2014	-6.31	< 0.001	2014-2019	-2.41	< 0.001	N/A	N/A	N/A	N/A	N/A	N/A
		All GI cancers	-2.91	< 0.001	1990-1994	-1.31	< 0.001	1994-2000	-1.92	< 0.001	2000-2004	-3.77	< 0.001	2004-2013	-5.03	< 0.001	2013-2016	-2.18	0.001	2016-2019	-0.13	0.601
	Male	Colon and rectum cancer	1.38	< 0.001	1990-1996	-1.03	< 0.001	1996-1999	1.18	0.053	1999-2004	6.46	< 0.001	2004-2011	1.64	< 0.001	2011-2016	-0.99	< 0.001	2016-2019	1.59	< 0.001
		Esophageal cancer	-1.93	< 0.001	1990-1997	-1.18	< 0.001	1997-2004	2.45	< 0.001	2004-2007	-4.15	< 0.001	2007-2014	-5.95	< 0.001	2014-2017	-3.34	< 0.001	2017-2019	0.35	0.572
		Gallbladder and biliary tract cancer	0.53	< 0.001	1990-1995	-2.49	< 0.001	1995-1998	-0.82	0.304	1998-2001	4.94	< 0.001	2001-2004	7.62	< 0.001	2004-2008	1.66	0.001	2008-2019	-1.13	< 0.001
		Liver cancer	-3.44	< 0.001	1990-1996	1.59	< 0.001	1996-2000	-4.74	< 0.001	2000-2005	-16.87	< 0.001	2005-2012	-1.84	< 0.001	2012-2019	2.00	< 0.001	N/A	N/A	N/A
		Pancreatic cancer	1.71	< 0.001	1990-1995	-1.25	< 0.001	1995-1999	2.47	< 0.001	1999-2004	4.66	< 0.001	2004-2012	2.17	< 0.001	2012-2016	-0.49	< 0.001	2016-2019	2.63	< 0.001
		Stomach cancer	-2.21	< 0.001	1990-1996	-3.03	< 0.001	1996-1999	-0.26	0.751	1999-2004	3.67	< 0.001	2004-2008	-4.17	< 0.001	2008-2015	-4.99	< 0.001	2015-2019	-2.66	< 0.001
		All GI cancers	-1.91	< 0.001	1990-1993	-0.15	0.699	1993-2000	-1.13	< 0.001	2000-2014	-3.07	< 0.001	2004-2019	-0.79	< 0.001	N/A	N/A	N/A	N/A	N/A	N/A

GI: Gastrointestinal; AAPC: Average annual percent change; APC: Annual percent change; ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; ASDR: Age-standardized disability-adjusted life-year rate; N/A: Not applicable.

As for the burden of specific GI cancers, three main patterns of temporal trends were identified for ASIR, ASMR, and ASDR among working-age individuals over three decades in China. First, an increasing trend was observed for colon, rectal, and pancreatic cancer. Second, a declining trend was observed in esophageal, liver, and stomach cancers. Third, stability was investigated in gallbladder and biliary tract cancers.

Burden of GI cancers among working-age population by age in China between 1990 and 2019

Figure 1 displays the burden of specific GI cancers among working-age people by age from 1990 to 2019 in China. Over the time period, the younger subpopulations were recorded with more incidence, mortality, and DALYs of colon and rectal cancer and liver cancer, while the older participants were observed with more incidence, mortality, and DALYs for esophageal cancer, gallbladder and biliary tract cancer, pancreatic cancer, and stomach cancer. Interestingly, there was an upward trend in the percentage of gallbladder and biliary tract cancer, pancreatic cancer, and colon and rectal cancer, and a downward trend in the percentage of liver cancer and esophageal cancers within each age group of participants over the three decades. Moreover, an upward trend was identified for people aged 15-34 years in the proportion of incidence cases with stomach cancer.

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Figure 1 The burden of specific gastrointestinal cancers among working-age people by age from 1990 to 2019 in China. A: The number of incident cases; B: The number of mortality; C: Disability-adjusted life-years. DALYs: Disability-adjusted life-years.

Figure 2 presents the temporal trends in the crude rates of GI cancer incidence, mortality, and DALYs with age for overall participants. Generally, the percentages of incidence, mortality, and DALYs of GI cancers increase with age from younger to older among working-age individuals in China. Specifically, three trend patterns in the incidence, mortality, and DALYs of GI cancers with age were determined in the study population. First, increasing trends in the CIR, CMR, and CDR were examined for colon and rectal cancer, gallbladder and biliary tract cancer, and pancreatic cancer. Second, declining trends in CDR, CMR, and CIR were observed in both liver and esophageal cancers. Third, for stomach cancer, an increasing trend in the CIR and decreasing trends in the CMR and CDR were identified among the participants (Table 3).

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Figure 2 Temporal in crude rates of gastrointestinal cancers’ incidence, mortality and disability-adjusted life-years with age among overall participants from 1990 to 2019. A: Incidence rate; B: Mortality rate; C: Disability-adjusted life-years rate. DALYs: Disability-adjusted life-years.

Table 3 Temporal trends in burden of gastrointestinal cancers by age group among working-age population in China 1990-2019.

Age-group	Gender	Type of GI cancers	CIR			CMR			CDR
Age-group	Gender	Type of GI cancers	AAPC	95%UI	P value	AAPC	95%UI	P value	AAPC	95%UI	P value
15-19 years	Overall	Colon and rectum cancer	0.75	0.51 to 1.00	< 0.001	-1.58	-1.87 to -1.30	< 0.001	-1.55	-1.85 to -1.25	< 0.001
		Esophageal cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Gallbladder and biliary tract cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Liver cancer	-4.06	-4.47 to -3.65	< 0.001	-4.55	-5.17 to -3.92	< 0.001	-4.55	-5.16 to -3.93	< 0.001
		Pancreatic cancer	-0.14	-0.40 to 0.13	0.31	-0.25	-0.51 to 0.01	0.06	-0.26	-0.51 to 0.00	0.051
		Stomach cancer	-0.64	-0.88 to -0.41	< 0.001	-2.95	-3.16 to -2.73	< 0.001	-2.92	-3.13 to -2.70	< 0.001
		All GI cancers	-1.03	-1.19 to -0.86	< 0.001	-3.05	-3.30 to -2.81	< 0.001	-3.01	-3.26 to -2.77	< 0.001
	Female	Colon and rectum cancer	0.58	0.27 to 0.90	< 0.001	-1.85	-2.05 to -1.65	< 0.001	-1.81	-2.13 to -1.49	< 0.001
		Esophageal cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Gallbladder and biliary tract cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Liver cancer	-4.15	-4.45 to -3.86	< 0.001	-4.77	-5.08 to -4.46	< 0.001	-4.77	-5.07 to -4.46	< 0.001
		Pancreatic cancer	-0.62	-0.97 to -0.27	< 0.001	-0.77	-1.11 to -0.44	< 0.001	-0.78	-1.12 to -0.43	< 0.001
		Stomach cancer	-1.38	-1.84 to -0.91	< 0.001	-3.38	-3.65 to -3.11	< 0.001	-3.35	-3.63 to -3.08	< 0.001
		All GI cancers	-1.18	-1.44 to -0.92	< 0.001	-3.19	-3.46 to -2.91	< 0.001	-3.15	-3.43 to -2.87	< 0.001
	Male	Colon and rectum cancer	0.94	0.49 to 1.39	< 0.001	-1.48	-1.82 to -1.15	< 0.001	-1.51	-1.95 to -1.07	< 0.001
		Esophageal cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Gallbladder and biliary tract cancer	NA	NA	NA	NA	NA	NA	NA	NA	NA
		Liver cancer	-4.09	-4.57 to -3.62	< 0.001	-4.55	-5.27 to -3.83	< 0.001	-4.55	-5.26 to -3.84	< 0.001
		Pancreatic cancer	0.04	-0.31 to 0.39	0.834	-0.07	-0.43 to 0.29	0.697	-0.08	-0.43 to 0.28	0.665
		Stomach cancer	-0.29	-0.54 to -0.04	< 0.05	-2.67	-2.96 to -2.39	< 0.001	-2.64	-2.92 to -2.35	< 0.001
		All GI cancers	-1.00	-1.31 to -0.68	< 0.001	-3.03	-3.29 to -2.77	< 0.001	-2.99	-3.25 to -2.73	< 0.001
20-24 years	Overall	Colon and rectum cancer	2.36	1.73 to 2.99	< 0.001	-0.22	-0.57 to 0.13	0.213	-0.15	-0.49 to 0.20	0.403
		Esophageal cancer	-0.85	-1.66 to -0.04	0.041	-1.85	-2.47 to -1.21	< 0.001	-1.83	-2.46 to -1.20	< 0.001
		Gallbladder and biliary tract cancer	-0.67	-1.28 to -0.05	0.035	-1.4	-1.99 to -0.82	< 0.001	-1.40	-1.98 to -0.81	< 0.001
		Liver cancer	-2.64	-2.95 to -2.32	< 0.001	-3.2	-4.05 to -2.34	< 0.001	-3.20	-4.04 to -2.34	< 0.001
		Pancreatic cancer	0.59	-0.11 to 1.29	0.097	0.48	-0.21 to -1.17	0.17	0.48	-0.20 to 1.17	0.17
		Stomach cancer	0.55	-0.26 to 1.36	0.183	-1.62	-2.44 to -0.79	< 0.001	-1.59	-2.40 to -0.76	< 0.001
		All GI cancers	0.22	-0.38 to 0.82	0.472	-1.79	-2.19 to -1.39	< 0.001	-1.75	-2.15 to -1.35	< 0.001
	Female	Colon and rectum cancer	1.92	1.41 to 2.44	< 0.001	-0.68	-1.54 to 0.19	0.126	-0.60	-1.46 to 0.26	0.173
		Esophageal cancer	-1.08	-2.05 to -0.11	0.029	-3.08	-3.77 to -2.38	< 0.001	-3.04	-3.73 to -2.34	< 0.001
		Gallbladder and biliary tract cancer	-0.87	-1.60 to -0.14	0.019	-1.77	-2.58 to -0.95	< 0.001	-1.76	-2.57 to -0.95	< 0.001
		Liver cancer	-3.25	-3.51 to -3.00	< 0.001	-3.71	-4.97 to -2.44	< 0.001	-3.71	-4.94 to -2.46	< 0.001
		Pancreatic cancer	-0.15	-0.80 to 0.50	0.653	-0.14	-0.80 to 0.52	0.675	-0.14	-0.79 to 0.52	0.675
		Stomach cancer	-0.32	-1.25 to 0.62	0.5	-2.32	-3.25 to -1.38	< 0.001	-2.29	-3.21 to -1.35	< 0.001
		All GI cancers	-0.23	-0.63 to 0.17	0.263	-2.37	-3.45 to -1.29	< 0.001	-2.33	-3.40 to -1.25	< 0.001
	Male	Colon and rectum cancer	2.56	1.89 to 3.23	< 0.001	-0.02	-0.27 to 0.24	0.884	0.07	-0.19 to 0.32	0.612
		Esophageal cancer	-0.79	-1.38 to -0.19	0.01	-1.31	-1.85 to -0.77	< 0.001	-1.31	-1.85 to -0.76	< 0.001
		Gallbladder and biliary tract cancer	-0.56	-1.23 to 0.10	0.097	-1.18	-1.83 to -0.53	< 0.001	-1.18	-1.83 to -0.52	< 0.001
		Liver cancer	-2.47	-2.71 to -2.22	< 0.001	-2.99	-3.45 to -2.53	< 0.001	-2.99	-3.45 to -2.54	< 0.001
		Pancreatic cancer	0.99	0.41 to 1.57	< 0.001	0.89	0.32 to 1.46	0.002	0.89	0.32 to 1.46	0.002
		Stomach cancer	1.13	0.38 to 1.89	0.003	-1.33	-1.95 to -0.71	< 0.001	-1.30	-1.92 to -0.67	< 0.001
		All GI cancers	0.38	-0.15 to 0.91	0.156	-1.63	-2.16 to -1.11	< 0.001	-1.60	-2.12 to -1.07	< 0.001
25-29 years	Overall	Colon and rectum cancer	2.77	2.04 to 3.50	< 0.001	0.30	-0.28 to 0.87	0.31	0.37	-0.19 to 0.95	0.198
		Esophageal cancer	-1.12	-2.35 to 0.13	0.078	-2.09	-3.20 to -0.96	< 0.001	-2.07	-3.19 to -0.95	< 0.001
		Gallbladder and biliary tract cancer	-0.53	-1.72 to 0.68	0.387	-1.26	-2.46 to -0.04	0.043	-1.25	-2.45 to -0.04	0.043
		Liver cancer	-2.40	-2.70 to -2.09	< 0.001	-2.95	-3.76 to -2.13	< 0.001	-2.94	-3.75 to -2.13	< 0.001
		Pancreatic cancer	0.84	-0.03 to 0.71	0.057	0.74	-0.11 to 1.60	0.089	0.74	-0.11 to 1.60	0.089
		Stomach cancer	0.55	-0.31 to 1.41	0.212	-1.75	-2.80 to -0.69	0.001	-1.71	-2.76 to -0.65	0.002
		All GI cancers	0.4	-0.32 to 1.12	0.278	-1.54	-2.14 to -0.94	< 0.001	-1.50	-2.10 to -0.90	< 0.001
	Female	Colon and rectum cancer	1.55	0.42 to 2.70	0.007	-0.72	-1.68 to 0.25	0.147	-0.65	-1.60 to 0.32	0.187
		Esophageal cancer	-1.67	-4.28 to 1.01	0.22	-3.62	-5.88 to -1.31	< 0.001	-3.58	-5.84 to -1.27	0.003
		Gallbladder and biliary tract cancer	-1.24	-2.94 to 0.49	0.159	-2.04	-4.36 to 0.33	0.091	-2.03	-4.35 to 0.34	0.093
		Liver cancer	-3.76	-4.08 to -3.43	< 0.001	-4.57	-5.94 to -3.18	< 0.001	-4.56	-5.93 to -3.17	< 0.001
		Pancreatic cancer	-0.02	-1.05 to 1.03	0.976	-0.18	-1.20 to 0.86	0.738	-0.17	-1.20 to 0.86	0.738
		Stomach cancer	-0.54	-2.30 to 1.26	0.555	-2.59	-4.44 to -0.71	0.007	-2.56	-4.41 to -0.68	0.008
		All GI cancers	-0.3	-1.22 to 0.63	0.525	-2.43	-4.15 to -0.67	0.007	-2.38	-4.11 to -0.63	0.007
	Male	Colon and rectum cancer	3.52	2.75 to 4.29	< 0.001	0.91	0.27 to 1.55	0.005	0.98	0.35 to 1.62	0.002
		Esophageal cancer	-1.00	-1.34 to -0.62	< 0.001	-1.55	-1.97 to -1.13	< 0.001	-1.55	-1.96 to -1.13	< 0.001
		Gallbladder and biliary tract cancer	-0.02	-0.77 to 0.73	0.96	-0.65	-1.37 to 0.07	0.076	-0.65	-1.37 to 0.07	0.078
		Liver cancer	-1.99	-2.30 to -1.67	< 0.001	-2.61	-2.61 to -2.82	< 0.001	-2.6	-2.81 to -2.39	< 0.001
		Pancreatic cancer	1.52	1.08 to 1.96	< 0.001	1.44	1.01 to 1.87	< 0.001	1.44	1.01 to 1.86	< 0.001
		Stomach cancer	1.44	0.90 to 2.00	< 0.001	-0.94	-1.35 to -0.52	< 0.001	-0.89	-1.30 to -0.48	< 0.001
		All GI cancers	0.85	0.56 to 1.13	< 0.001	-1.18	-1.46 to -0.90	< 0.001	-1.14	-1.41 to -0.86	< 0.001
30-34 years	Overall	Colon and rectum cancer	2.90	2.13 to 3.67	< 0.001	0.43	-0.42 to 1.28	0.324	0.50	-0.34 to 1.35	0.247
		Esophageal cancer	-0.95	-1.57 to -0.33	0.003	-1.74	-2.87 to -0.60	0.003	-1.73	-2.86 to -0.59	0.003
		Gallbladder and biliary tract cancer	-0.14	-0.96 to 0.69	0.737	-0.84	-1.64 to -0.04	0.038	-0.84	-1.63 to -0.04	0.041
		Liver cancer	-2.54	-2.75 to -2.34	< 0.001	-3.06	-3.76 to -2.36	< 0.001	-3.06	-3.75 to -2.36	< 0.001
		Pancreatic cancer	1.39	0.86 to 1.92	< 0.001	1.29	0.78 to 1.81	< 0.001	1.29	0.78 to 1.81	< 0.001
		Stomach cancer	0.37	-0.57 to 1.32	0.443	-2.02	-3.18 to -0.84	0.001	-1.98	-3.14 to -0.80	0.001
		All GI cancers	0.24	-0.46 to 0.94	0.508	-1.71	-2.59 to -0.82	< 0.001	-1.67	-2.56 to -0.78	< 0.001
	Female	Colon and rectum cancer	1.36	0.28 to 2.46	0.013	-1.28	-2.63 to 0.08	0.064	-1.21	-2.56 to 0.16	0.082
		Esophageal cancer	-1.93	-3.57 to -0.26	0.023	-3.87	-5.22 to -2.51	< 0.001	-3.84	-5.20 to -2.47	< 0.001
		Gallbladder and biliary tract cancer	-0.78	-1.96 to 0.41	0.197	-1.72	-2.84 to -0.58	0.003	-1.71	-2.84 to -0.57	0.003
		Liver cancer	-4.05	-4.34 to -3.76	< 0.001	-4.69	-5.73 to -3.63	< 0.001	-4.83	-6.60 to -3.04	< 0.001
		Pancreatic cancer	0.26	-1.31 to 1.85	0.751	0.11	-1.47 to 1.70	0.897	0.11	-1.48 to 1.72	0.896
		Stomach cancer	-0.97	-2.63 to 0.73	0.261	-3.18	-4.63 to -1.71	< 0.001	-3.15	-4.60 to -1.67	< 0.001
		All GI cancers	-0.65	-1.31 to 0.01	0.052	-2.89	-4.52 to -1.22	0.001	-2.86	-4.26 to -1.44	< 0.001
	Male	Colon and rectum cancer	3.88	2.99 to 4.78	< 0.001	1.25	0.63 to 1.87	< 0.001	1.32	0.70 to 1.94	< 0.001
		Esophageal cancer	-0.8	-1.52 to -0.08	0.029	-1.39	-2.39 to -0.38	0.007	-1.39	-2.38 to -0.38	0.007
		Gallbladder and biliary tract cancer	0.33	-0.59 to 1.26	0.485	-0.31	-1.20 to 0.59	0.494	-0.31	-1.20 to 0.59	0.502
		Liver cancer	-2.16	-2.39 to -1.94	< 0.001	-2.73	-3.31 to -2.14	< 0.001	-2.72	-3.30 to -2.14	< 0.001
		Pancreatic cancer	2.00	1.38 to 2.62	< 0.001	1.92	1.31 to 2.53	< 0.001	1.92	1.31 to 2.53	< 0.001
		Stomach cancer	1.27	0.50 to 2.05	0.001	-1.19	-1.79 to -0.59	< 0.001	-1.15	-1.75 to -0.54	< 0.001
		All GI cancers	0.65	0.14 to 1.16	0.013	-1.32	-2.01 to -0.61	< 0.001	-1.28	-1.97 to -0.58	< 0.001
35-39 years	Overall	Colon and rectum cancer	3.27	2.73 to 3.81	< 0.001	0.55	0.25 to 0.85	< 0.001	0.64	0.34 to 0.93	< 0.001
		Esophageal cancer	-1.73	-2.86 to -0.59	0.003	-2.23	-2.57 to -1.88	< 0.001	-2.22	-2.55 to -1.88	< 0.001
		Gallbladder and biliary tract cancer	-0.84	-1.63-0.04	0.041	-0.63	-0.93 to -0.32	< 0.001	-0.62	-0.92 to -0.31	< 0.001
		Liver cancer	-3.06	-3.75 to -2.36	< 0.001	-3.57	-3.95 to -3.18	< 0.001	-3.56	-3.94 to -3.18	< 0.001
		Pancreatic cancer	1.57	1.23 to 1.92	< 0.001	1.47	1.11 to 1.83	< 0.001	1.47	1.12 to 1.83	< 0.001
		Stomach cancer	-0.19	-0.56 to 0.19	0.332	-2.26	-2.47 to -2.04	< 0.001	-2.22	-2.44 to -2.01	< 0.001
		All GI cancers	-1.67	-2.56 to -0.78	< 0.001	-2.1	-2.36 to -1.83	< 0.001	-2.06	-2.42 to -1.69	< 0.001
	Female	Colon and rectum cancer	1.54	1.27 to 1.82	< 0.001	-1.12	-1.40 to -0.84	< 0.001	-1.04	-1.32 to -0.76	< 0.001
		Esophageal cancer	-3.84	-5.20 to -2.47	< 0.001	-4.16	-4.58 to -3.74	< 0.001	-4.13	-4.56 to -3.70	< 0.001
		Gallbladder and biliary tract cancer	-1.71	-2.84 to -0.57	0.003	-1.67	-2.13 to -1.20	< 0.001	-1.66	-2.14 to -1.18	< 0.001
		Liver cancer	-4.83	-6.60 to -3.04	< 0.001	-5.10	-5.41 to -4.79	< 0.001	-5.07	-5.41 to -4.73	< 0.001
		Pancreatic cancer	0.47	0.23 to 0.71	< 0.001	0.32	0.08 to 0.55	0.008	0.32	0.08 to 0.55	0.008
		Stomach cancer	-1.51	-1.94 to -1.08	< 0.001	-3.37	-3.80 to -2.93	< 0.001	-3.34	-3.79 to -2.89	< 0.001
		All GI cancers	-2.86	-4.26 to -1.44	< 0.001	-3.07	-3.35 to -2.78	< 0.001	-3.03	-3.31 to -2.74	< 0.001
	Male	Colon and rectum cancer	4.29	3.72 to 4.87	< 0.001	1.42	0.83 to 2.01	< 0.001	1.51	0.93 to 2.10	< 0.001
		Esophageal cancer	-1.39	-2.38 to -0.38	0.007	-1.84	-2.29 to -1.39	< 0.001	-1.84	-2.28 to -1.39	< 0.001
		Gallbladder and biliary tract cancer	-0.31	-1.20 to 0.59	0.502	-0.01	-0.41 to 0.40	0.98	0.00	-0.40 to 0.41	0.992
		Liver cancer	-2.72	-3.30 to -2.14	< 0.001	-3.26	-3.80 to -2.70	< 0.001	-3.25	-3.80 to -2.70	< 0.001
		Pancreatic cancer	1.98	1.42 to 2.55	< 0.001	1.89	1.33 to 2.45	< 0.001	1.89	1.33 to 2.45	< 0.001
		Stomach cancer	0.61	0.12 to 1.09	0.014	-1.54	-1.94 to -1.14	< 0.001	-1.51	-1.91 to -1.11	< 0.001
		All GI cancers	-1.28	-1.97 to -0.58	< 0.001	-1.73	-2.08 to -1.39	< 0.001	-1.70	-2.04 to -1.35	< 0.001
40-44 years	Overall	Colon and rectum cancer	3.39	3.06 to 3.72	< 0.001	0.61	0.24 to 0.97	0.001	0.70	0.34 to 1.06	< 0.001
		Esophageal cancer	-2.47	-2.89 to -2.05	< 0.001	-3.07	-3.47 to -2.68	< 0.001	-3.06	-3.46 to -2.66	< 0.001
		Gallbladder and biliary tract cancer	0.52	0.19 to 0.85	0.002	-0.21	-0.48 to 0.06	0.122	-0.21	-0.48 to 0.07	0.141
		Liver cancer	-2.98	-3.23 to -2.74	< 0.001	-3.66	-4.08 to -3.24	< 0.001	-3.65	-4.07 to -3.23	< 0.001
		Pancreatic cancer	2.15	1.91 to 2.40	< 0.001	2.05	1.81 to 2.29	< 0.001	2.05	1.81 to 2.29	< 0.001
		Stomach cancer	-0.42	-0.82 to -0.01	0.042	-2.59	-2.97 to -2.21	< 0.001	-2.56	-2.94 to -2.18	< 0.001
		All GI cancers	-0.47	-0.94 to 0.01	0.057	-2.37	-2.71 to -2.03	< 0.001	-2.33	-2.68 to -1.98	< 0.001
	Female	Colon and rectum cancer	1.66	1.30 to 2.02	< 0.001	-1.02	-1.31 to -0.72	< 0.001	-0.93	-1.23 to -0.63	< 0.001
		Esophageal cancer	-3.26	-3.66 to -2.86	< 0.001	-5.02	-5.56 to -4.49	< 0.001	-5.01	-5.45 to -4.56	< 0.001
		Gallbladder and biliary tract cancer	-0.45	-0.60 to -0.30	< 0.001	-1.34	-1.55 to -1.13	< 0.001	-1.33	-1.55 to -1.12	< 0.001
		Liver cancer	-4.54	-4.81 to -4.26	< 0.001	-5.20	-5.56 to -4.84	< 0.001	-5.20	-5.56 to -4.84	< 0.001
		Pancreatic cancer	1.05	0.56 to 1.55	< 0.001	0.89	0.38 to 1.41	0.001	0.89	0.38 to 1.40	0.001
		Stomach cancer	-1.63	-1.91 to -1.35	< 0.001	-3.63	-3.89 to -3.37	< 0.001	-3.61	-3.86 to -3.35	< 0.001
		All GI cancers	-1.12	-1.34 to -0.89	< 0.001	-3.26	-3.75 to -2.77	< 0.001	-3.22	-3.70 to -2.73	< 0.001
	Male	Colon and rectum cancer	4.46	4.03 to 4.88	< 0.001	1.63	1.15 to 2.11	< 0.001	1.72	1.25 to 2.20	< 0.001
		Esophageal cancer	-2.24	-2.70 to -1.77	< 0.001	-2.71	-3.15 to -2.26	< 0.001	-2.70	-3.14 to -2.25	< 0.001
		Gallbladder and biliary tract cancer	1.15	0.94 to 1.36	< 0.001	0.53	0.34 to 0.73	< 0.001	0.54	0.35 to 0.77	< 0.001
		Liver cancer	-2.62	-2.89 to -2.35	< 0.001	-3.26	-3.43 to -2.79	< 0.001	-3.26	-3.72 to -2.78	< 0.001
		Pancreatic cancer	2.63	2.34 to 2.91	< 0.001	2.53	2.25 to 2.82	< 0.001	2.54	2.25 to 2.82	< 0.001
		Stomach cancer	0.07	-0.30 to 0.44	0.702	-2.04	-2.51 to -1.57	< 0.001	-2.01	-2.48 to -1.53	< 0.001
		All GI cancers	-0.18	-0.68 to 0.33	0.488	-2.03	-2.40 to -1.67	< 0.001	-2.00	-2.37 to -1.63	< 0.001
45-49 years	Overall	Colon and rectum cancer	2.96	2.43 to 3.49	< 0.001	0.54	0.14 to 0.94	0.008	0.63	0.23 to 1.02	0.002
		Esophageal cancer	-2.14	-2.91 to -1.37	< 0.001	-2.82	-3.50 to -2.13	< 0.001	-2.81	-3.49 to -2.12	< 0.001
		Gallbladder and biliary tract cancer	0.10	-0.25 to 0.45	0.591	-0.25	-0.60 to 0.11	0.174	-0.24	-0.60 to 0.11	0.182
		Liver cancer	-3.43	-3.88 to -2.97	< 0.001	-3.93	-4.77 to -3.08	< 0.001	-3.92	-4.76 to -3.08	< 0.001
		Pancreatic cancer	1.61	1.34 to 1.88	< 0.001	1.54	1.27 to 1.82	< 0.001	1.55	1.27 to 1.82	< 0.001
		Stomach cancer	-1.04	-1.61 to -0.46	< 0.001	-2.87	-3.62 to -2.11	< 0.001	-2.84	-3.59 to -2.08	< 0.001
		All GI cancers	-0.93	-1.22 to -0.65	< 0.001	-2.51	-2.96 to -2.05	< 0.001	-2.47	-2.93 to -2.02	< 0.001
	Female	Colon and rectum cancer	1.76	1.01 to 2.51	< 0.001	-0.75	-1.40 to -0.09	0.025	-0.66	-1.32 to -0.01	0.047
		Esophageal cancer	-3.07	-3.64 to -2.50	< 0.001	-4.72	-5.18 to -4.26	< 0.001	-4.69	-5.15 to -4.22	< 0.001
		Gallbladder and biliary tract cancer	-0.58	-1.48 to 0.33	0.211	-1.01	-1.92 to -0.10	0.03	-1.01	-1.92 to -0.09	< 0.05
		Liver cancer	-4.72	-4.92 to -4.51	< 0.001	-5.02	-6.14 to -3.89	< 0.001	-5.02	-6.13 to -3.90	< 0.001
		Pancreatic cancer	0.88	0.06 to 1.71	0.035	0.79	-0.04 to 1.61	0.061	0.79	-0.04 to 1.62	0.061
		Stomach cancer	-1.98	-3.07 to -0.89	< 0.001	-3.56	-4.61 to -2.50	< 0.001	-3.53	-4.59 to -2.47	< 0.001
		All GI cancers	-1.4	-2.26 to -0.54	0.001	-3.04	-3.76 to -2.32	< 0.001	-3.00	-3.72 to -2.28	< 0.001
	Male	Colon and rectum cancer	3.66	2.87 to 4.45	< 0.001	1.14	0.62 to 1.67	< 0.001	1.23	0.71 to 1.75	< 0.001
		Esophageal cancer	-1.91	-2.30 to -1.51	< 0.001	-2.39	-2.80 to -1.97	< 0.001	-2.38	-2.79 to -1.97	< 0.001
		Gallbladder and biliary tract cancer	0.6	0.30 to 0.89	< 0.001	0.31	0.02 to 0.61	0.037	0.32	0.02 to 0.61	0.035
		Liver cancer	-3.14	-3.56 to -2.71	< 0.001	-3.63	-4.16 to -3.09	< 0.001	-3.62	-4.15 to -3.09	< 0.001
		Pancreatic cancer	2.06	1.52 to 2.59	< 0.001	1.91	1.32 to 2.52	< 0.001	1.92	1.32 to 2.52	< 0.001
		Stomach cancer	-0.69	-1.33 to -0.04	0.038	-2.46	-3.11 to -1.81	< 0.001	-2.43	-3.08 to -1.78	< 0.001
		All GI cancers	-0.7	-1.03 to -0.36	< 0.001	-2.26	-2.73 to -1.79	< 0.001	-2.23	-2.70 to -1.76	< 0.001
50-54 years	Overall	Colon and rectum cancer	2.92	2.65 to 3.20	< 0.001	0.45	0.22 to 0.67	< 0.001	0.54	0.32 to 0.75	< 0.001
		Esophageal cancer	-2.18	-2.47 to -1.88	< 0.001	-2.61	-2.90 to -2.32	< 0.001	-2.60	-2.89 to -2.31	< 0.001
		Gallbladder and biliary tract cancer	0.21	-0.04 to 0.45	0.094	-0.04	-0.28 to 0.20	0.734	-0.04	-0.27 to 0.20	0.752
		Liver cancer	-3.70	-4.01 to -3.39	< 0.001	-4.10	-4.38 to -3.82	< 0.001	-4.10	-4.38 to -3.82	< 0.001
		Pancreatic cancer	1.03	0.71 to 1.36	< 0.001	0.98	0.66 to 1.30	< 0.001	0.98	0.67 to 1.30	< 0.001
		Stomach cancer	-1.40	-1.74 to -1.09	< 0.001	-2.92	-3.20 to -2.64	< 0.001	-2.89	-3.17 to -2.61	< 0.001
		All GI cancers	-1.07	-1.29 to -0.86	< 0.001	-2.54	-2.73 to -2.35	< 0.001	-2.51	-2.70 to -2.32	< 0.001
	Female	Colon and rectum cancer	1.48	1.22 to 1.73	< 0.001	-1.01	-1.45 to -0.58	< 0.001	-0.92	-1.33 to -0.50	< 0.001
		Esophageal cancer	-3.93	-4.36 to -3.49	< 0.001	-5.18	-5.72 to -4.63	< 0.001	-5.15	-5.70 to -4.60	< 0.001
		Gallbladder and biliary tract cancer	-0.60	-1.27 to 0.08	0.084	-0.92	-1.57 to -0.25	0.007	-0.91	-1.57 to -0.25	0.007
		Liver cancer	-4.68	-4.87 to -4.48	< 0.001	-5.00	-5.44 to -4.56	< 0.001	-5.00	-5.42 to -4.57	< 0.001
		Pancreatic cancer	0.63	0.23 to 1.04	0.002	0.57	0.16 to 0.98	0.006	0.57	0.18 to 0.97	0.005
		Stomach cancer	-2.39	-2.67 to -2.10	< 0.001	-3.71	-3.96 to -3.46	< 0.001	-3.69	-3.93 to -3.45	< 0.001
		All GI cancers	-1.58	-1.83 to -1.32	< 0.001	-3.21	-3.56 to -2.87	< 0.001	-3.18	-3.51 to -2.85	< 0.001
	Male	Colon and rectum cancer	3.93	3.65 to 4.21	< 0.001	1.47	1.21 to 1.73	< 0.001	1.52	1.14 to 1.89	< 0.001
		Esophageal cancer	-1.61	-1.85 to -1.36	< 0.001	-1.99	-2.30 to -1.69	< 0.001	-1.99	-2.29 to -1.68	< 0.001
		Gallbladder and biliary tract cancer	0.82	0.37 to 1.27	< 0.001	0.65	0.44 to 0.86	< 0.001	0.65	0.45 to 0.86	< 0.001
		Liver cancer	-3.34	-3.65 to -3.02	< 0.001	-3.74	-4.05 to -3.43	< 0.001	-3.74	-4.04 to -3.43	< 0.001
		Pancreatic cancer	1.36	0.93 to 1.79	< 0.001	1.31	0.88 to 1.75	< 0.001	1.31	0.88 to 1.74	< 0.001
		Stomach cancer	-0.94	-1.31 to -0.57	< 0.001	-2.55	-2.81 to -2.28	< 0.001	-2.52	-2.79 to -2.25	< 0.001
		All GI cancers	-0.78	-0.97 to -0.58	< 0.001	-2.21	-2.44 to -1.97	< 0.001	-2.18	-2.41 to -1.95	< 0.001
55-59years	Overall	Colon and rectum cancer	2.81	2.14 to 3.49	< 0.001	0.37	-0.16 to 0.89	0.169	0.46	-0.06 to 0.98	0.081
		Esophageal cancer	-2.27	-2.73 to -1.80	< 0.001	-2.65	-3.11 to -2.19	< 0.001	-2.65	-3.11 to -2.18	< 0.001
		Gallbladder and biliary tract cancer	0.391	-0.22 to 1.01	0.209	0.09	-0.54 to 0.71	0.788	0.08	-0.55 to 0.72	0.797
		Liver cancer	-3.59	-3.81 to -3.38	< 0.001	-3.92	-4.47 to -3.37	< 0.001	-3.92	-4.46 to -3.37	< 0.001
		Pancreatic cancer	1.13	0.84 to 1.41	< 0.001	1.08	0.80 to 1.36	< 0.001	1.08	0.79 to 1.36	< 0.001
		Stomach cancer	-1.50	-2.06 to -1.94	< 0.001	-2.89	-3.45 to -2.33	< 0.001	-2.87	-3.43 to -2.31	< 0.001
		All GI cancers	-1.00	-1.26 to -0.75	< 0.001	-2.37	-2.68 to -2.07	< 0.001	-2.34	-2.65 to -2.04	< 0.001
	Female	Colon and rectum cancer	1.74	0.72 to 2.78	< 0.001	-0.56	-1.25 to 0.12	0.108	-0.47	-1.15 to 0.21	0.176
		Esophageal cancer	-4.12	-4.71 to -3.52	< 0.001	-4.99	-5.71 to -4.26	< 0.001	-4.97	-5.70 to -4.24	< 0.001
		Gallbladder and biliary tract cancer	-0.43	-1.58 to 0.74	0.471	-0.79	-1.96 to 0.40	0.193	-0.79	-1.97 to 0.41	0.197
		Liver cancer	-4.47	-4.63 to -4.30	< 0.001	-4.71	-5.23 to -4.18	< 0.001	-4.71	-5.23 to -4.18	< 0.001
		Pancreatic cancer	0.91	0.30 to 1.52	< 0.001	0.85	0.24 to 1.47	0.006	0.85	0.23 to 1.47	0.007
		Stomach cancer	-2.43	-3.22 to -1.63	< 0.001	-3.59	-4.41 to -2.76	< 0.001	-3.57	-4.40 to -2.74	< 0.001
		All GI cancers	-1.54	-2.14 to -0.94	< 0.001	-3.05	-3.59 to -2.51	< 0.001	-3.01	-3.55 to -2.47	< 0.001
	Male	Colon and rectum cancer	3.64	3.31 to 3.97	< 0.001	1.25	0.84 to 1.66	< 0.001	1.33	0.77 to 1.89	< 0.001
		Esophageal cancer	-1.68	-2.00 to -1.36	< 0.001	-1.97	-2.30 to -1.65	< 0.001	-1.97	-2.30 to -1.64	< 0.001
		Gallbladder and biliary tract cancer	1.09	0.88 to 1.29	< 0.001	0.76	0.42 to 1.09	< 0.001	0.75	0.41 to 1.09	< 0.001
		Liver cancer	-3.25	-3.50 to -3.00	< 0.001	-3.60	-4.17 to -3.03	< 0.001	-3.6	-4.16 to -3.04	< 0.001
		Pancreatic cancer	1.37	1.09 to 1.65	< 0.001	1.33	1.05 to 1.61	< 0.001	1.33	1.05 to 1.61	< 0.001
		Stomach cancer	-1.00	-1.28 to -0.73	< 0.001	-2.55	-2.84 to -2.26	< 0.001	-2.53	-2.82 to -2.23	< 0.001
		All GI cancers	-0.76	-1.14 to -0.38	< 0.001	-2.04	-2.29 to -1.79	< 0.001	-2.01	-2.26 to -1.76	< 0.001
60-64 years	Overall	Colon and rectum cancer	3.02	2.65 to 3.40	< 0.001	0.66	0.27 to 1.06	0.001	0.77	0.38 to 1.15	< 0.001
		Esophageal cancer	-1.90	-2.10 to -1.70	< 0.001	-2.28	-2.48 to -2.09	< 0.001	-2.28	-2.47 to -2.08	< 0.001
		Gallbladder and biliary tract cancer	0.61	0.21 to 1.01	0.003	0.37	0.15 to 0.59	0.001	0.37	0.14 to 0.59	0.001
		Liver cancer	-3.27	-3.50 to -3.04	< 0.001	-3.65	-4.13 to -3.16	< 0.001	-3.65	-4.13 to -3.16	< 0.001
		Pancreatic cancer	1.69	1.55 to 1.83	< 0.001	1.65	1.48 to 1.82	< 0.001	1.64	1.48 to 1.81	< 0.001
		Stomach cancer	-1.07	-1.39 to -0.74	< 0.001	-2.43	-2.67 to -2.19	< 0.001	-2.41	-2.64 to -2.17	< 0.001
		All GI cancers	-0.67	-0.90 to -0.43	< 0.001	-1.97	-2.14 to -1.80	< 0.001	-1.93	-2.10 to -1.76	< 0.001
	Female	Colon and rectum cancer	2.09	1.45 to 2.74	< 0.001	-0.41	-0.85 to 0.03	0.07	-0.31	-0.75 to 0.13	0.167
		Esophageal cancer	-3.61	-4.18 to -3.04	< 0.001	-4.48	-5.06 to -3.89	< 0.001	-4.46	-5.05 to -3.87	< 0.001
		Gallbladder and biliary tract cancer	0.10	-0.40 to 0.60	0.694	-0.23	-0.71 to 0.26	0.359	-0.23	-0.71 to 0.26	0.363
		Liver cancer	-3.99	-4.15 to -3.83	< 0.001	-4.23	-4.47 to -3.98	< 0.001	-4.23	-4.47 to -3.98	< 0.001
		Pancreatic cancer	1.4	1.19 to 1.61	< 0.001	1.35	1.11 to 1.59	< 0.001	1.33	1.13 to 1.53	< 0.001
		Stomach cancer	-2.21	-2.70 to -1.71	< 0.001	-3.30	-3.78 to -2.82	< 0.001	-3.29	-3.77 to -2.81	< 0.001
		All GI cancers	-1.32	-1.61 to -1.02	< 0.001	-2.67	-3.00 to -2.34	< 0.001	-2.63	-2.96 to -2.31	< 0.001
	Male	Colon and rectum cancer	3.77	3.43 to 4.12	< 0.001	1.43	1.09 to 1.77	< 0.001	1.53	1.20 to 1.86	< 0.001
		Esophageal cancer	-1.26	-1.41 to -1.10	< 0.001	-1.55	-1.72 to -1.39	< 0.001	-1.57	-1.70 to -1.44	< 0.001
		Gallbladder and biliary tract cancer	1.14	0.86 to 1.43	< 0.001	0.90	0.60 to 1.19	< 0.001	0.90	0.60 to 1.19	< 0.001
		Liver cancer	-2.94	-3.32 to -2.56	< 0.001	-3.35	-4.02 to -2.68	< 0.001	-3.35	-4.01 to -2.68	< 0.001
		Pancreatic cancer	1.93	1.74 to 2.12	< 0.001	1.88	1.69 to 2.07	< 0.001	1.88	1.69 to 2.07	< 0.001
		Stomach cancer	-0.58	-0.97 to -0.19	0.004	-2.08	-2.31 to -1.85	< 0.001	-1.98	-2.24 to -1.73	< 0.001
		All GI cancers	-0.32	-0.56 to -0.09	0.006	-1.62	-1.82 to -1.43	< 0.001	-1.59	-1.77 to -1.40	< 0.001
15-64 years	Overall	Colon and rectum cancer	0.77	0.38 to 1.15	< 0.001	2.11	2.00 to 2.23	< 0.001	1.98	1.89 to 2.07	< 0.001
		Esophageal cancer	-0.23	-0.39 to -0.07	0.004	-0.64	-0.83 to -0.46	< 0.001	-0.72	-0.88 to -0.56	< 0.001
		Gallbladder and biliary tract cancer	2.05	1.85 to 2.26	< 0.001	1.79	1.51 to 2.07	< 0.001	1.59	1.26 to 1.93	< 0.001
		Liver cancer	-1.82	-2.09 to -1.56	< 0.001	-2.24	-2.75 to -1.72	< 0.001	-2.38	-2.84 to -1.91	< 0.001
		Pancreatic cancer	3.18	2.98 to 3.37	< 0.001	3.15	2.95 to 3.35	< 0.001	3.02	2.80 to 3.24	< 0.001
		Stomach cancer	0.63	0.46 to 0.80	< 0.001	-0.93	-1.13 to -0.73	< 0.001	-1.03	-1.15 to -0.90	< 0.001
		All GI cancers	0.88	0.72 to 1.03	< 0.001	-0.57	-0.73 to -0.41	< 0.001	-0.69	-0.83 to -0.56	< 0.001
	Female	Colon and rectum cancer	-0.31	-0.75 to 0.13	0.167	0.96	0.84 to 1.08	< 0.001	0.80	0.70 to 0.91	< 0.001
		Esophageal cancer	-1.78	-2.10 to -1.46	< 0.001	-2.84	-3.19 to -2.49	< 0.001	-2.89	-3.19 to -2.58	< 0.001
		Gallbladder and biliary tract cancer	1.56	1.21 to 1.91	< 0.001	1.22	0.87 to 1.57	< 0.001	1.01	0.87 to 1.14	< 0.001
		Liver cancer	-2.77	-3.12 to -2.43	< 0.001	-3.04	-3.43 to -2.65	< 0.001	-3.24	-3.61 to -2.86	< 0.001
		Pancreatic cancer	2.84	2.67 to 3.00	< 0.001	2.80	2.63 to 2.96	< 0.001	2.61	2.40 to 2.83	< 0.001
		Stomach cancer	-0.42	-0.52 to -0.32	< 0.001	-1.79	-1.88 to -1.70	< 0.001	-1.90	-2.15 to -1.65	< 0.001
		All GI cancers	0.38	0.15 to 0.60	0.001	-1.23	-1.31 to -1.15	< 0.001	-1.37	-1.48 to -1.25	< 0.001
	Male	Colon and rectum cancer	1.53	1.20 to 1.86	< 0.001	2.87	2.72 to 3.01	< 0.001	2.74	2.59 to 2.89	< 0.001
		Esophageal cancer	0.21	0.03 to 0.39	0.023	-0.15	-0.36 to -0.06	0.174	-0.23	-0.43 to -0.03	0.022
		Gallbladder and biliary tract cancer	2.51	2.31 to 2.72	< 0.001	2.28	2.06 to 2.51	< 0.001	2.06	1.78 to 2.34	< 0.001
		Liver cancer	-1.54	-1.85 to -1.23	< 0.001	-2.00	-2.43 to -1.56	< 0.001	-2.11	-2.50 to -1.72	< 0.001
		Pancreatic cancer	3.40	3.17 to 3.62	< 0.001	3.37	3.15 to 3.59	< 0.001	3.26	3.03 to 3.49	< 0.001
		Stomach cancer	1.06	0.85 to 1.28	< 0.001	-0.57	-0.80 to -0.33	< 0.001	-0.62	-0.84 to -0.40	< 0.001
		All GI cancers	1.12	0.96 to 1.28	< 0.001	-0.33	-0.49 to -0.17	< 0.001	-0.41	-0.57 to -0.25	< 0.001

GI: Gastrointestinal; CIR: Crude incidence rate; CMR: Crude mortality rate; CDR: Crude disability-adjusted life-years rate; AAPC: Average annual percent change; 95%UI: 95% uncertainty interval; NA: Not available.

In addition to the trends in CIR, CMR, and CDR with age analyzed in all participants, the trends were also explored for participants stratified by age (Table 3). For individuals aged 15-29 years, an increasing trend was observed only in the CIR of colon and rectal cancers. Among people aged 35-54 years, increasing trends were observed in the CIR, CMR, and CDR of pancreatic and colorectal cancers. Within participants aged 60 + years, CIR, CMR and CDR remained at an increasing trend in pancreatic cancer, gallbladder and biliary tract cancer, and colon and rectum cancer. Additionally, in the other age groups, increasing trends in CIR, CMR, and CDR were observed for pancreatic cancer, whereas only CIR increased consistently for colon and rectal cancers over the decades.

Burden of GI cancers among working-age population by gender in China between 1990 and 2019

In 2019, the incidence, mortality, DALYs, CIR, CMR, and CDR of each type of GI cancer were higher in men than in women in all age groups (Figure 3). Moreover, for GI cancers, the male-to-female ratios of the age-standardized incidence, mortality, DALYs, CIR, CMR, and CDR were higher in 2019 than in 1990 (Table 4). From 1990 to 2019, for both men and women, a decreasing trend was observed in the ASIR, ASMR, and ASDR of esophageal, liver, and stomach cancers, whereas an increasing trend was observed for the ASIR, ASMR, and ASDR of pancreatic cancer. However, opposite trends were identified for men and women in either the ASMR or ASDR of colon and rectal cancer, and gallbladder and biliary tract cancer. Interestingly, the differences in the ASIR, ASMR, and ASDR of GI cancers between men and women increased from 1990 to 2019, suggesting a growing disparity in the GI cancer burden between sexes (Table 2).

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Figure 3 The burden of gastrointestinal cancers among working-age population by sex between 1990 and 2019 in China. A: Incident cases in 1990; B: Incident cases in 2019; C: Incidence rate in 1990; D: Incidence rate in 2019; E: Mortality cases in 1990; F: Mortality cases in 2019; G: Mortality rate in 1990; H: Mortality rate in 2019; I: Disability-adjusted life-years (DALYs) in 1990; J: DALYs in 2019; K: DALYs rate in 1990; L: DALYs rate in 2019. DALYs: Disability-adjusted life-years.

Table 4 Male-to-female ratio in burden of the specific gastrointestinal cancers among working-age population in China between 1990 and 2019.

	Incident cases		ASIR		Mortality		ASMR		DALYs		ASDR
Type of GI cancers	1990	2019	1990	2019	1990	2019	1990	2019	1990	2019	1990	2019
Colon and rectum cancer	1.25	2.06	1.14	2.04	1.25	2.08	1.14	2.05	1.26	2.12	1.15	2.09
Esophageal cancer	2.84	4.90	2.60	4.78	2.97	6.38	2.72	6.24	3.09	6.55	2.82	6.4
Gallbladder and biliary tract cancer	1.01	1.30	0.92	1.28	1.01	1.32	0.92	1.31	1.04	1.38	0.94	1.38
Liver cancer	3.34	4.59	3.03	4.57	3.33	4.41	3.02	4.4	3.44	4.68	3.13	4.67
Pancreatic cancer	1.71	1.96	1.56	1.95	1.71	1.97	1.56	1.97	1.74	2.05	1.59	2.05
Stomach cancer	2.17	3.26	2.03	3.13	2.15	3.01	2.01	2.91	2.05	2.94	1.93	2.81
All GI cancers	2.36	2.86	2.18	2.19	2.44	3.11	2.24	3.05	2.45	3.14	2.25	3.07

GI: Gastrointestinal; ASIR: Age-standardized incidence rate; ASMR: Age-standardized mortality rate; DALYs: Disability-adjusted life-years; ASDR: Age-standardized disability-adjusted life-year rate.

DISCUSSION

Based on the GBD 2019 data, using incidence cases, mortality cases, DALYS, ASIR, ASMR, and ASDR as single indicators of disease burden, this study aimed to estimate the burden of GI cancers among the working-age population in 1990 and 2019 and then to examine the trends in GI cancers over three decades in China. From 1990 to 2019, a decreasing trend was observed in the ASIR, ASMR, and ASDR of GI cancers, while an increasing trend was identified in the CIR of GI cancers among the working-age population in the recent period to 2016-2019 in China. Moreover, substantial discrepancies in the burden of GI cancers were observed between sexes, age groups, and cancer types.

A significant decline was identified in the ASIR, ASMR, and ASDR of GI cancers in the working-age population in China between 1990 and 2019. This finding is consistent with that reported in a previous study on the GI cancer burden among the general population in China[10]. Such a declining trend in the burden of GI cancers may be caused mainly by transitions in the risk factors of GI cancers, advances in medical technology, and population-based cancer prevention policies adopted by the Chinese government over the time period[21-24]. Specifically, the risk factors of GI cancers, such as tobacco use, unhealthy eating habits, and over-intake of sodium, have been favorably changing among Chinese people over time[21]. In addition, the development of new drugs, widespread implementation of early screening programs, and improvement of diagnostic and treatment approaches are largely responsible for the changes in trends of GI cancer burden observed in this study[22-24]. Additionally, the “Healthy China Action Plan (2019-2030)” and some population-based GI cancer prevention-oriented policies, e.g., the “The technical solutions for screening and early diagnosis and treatment of upper gastrointestinal cancer”, can provide easily-accessible medical service regarding GI cancers for people in China[25].

Interestingly, irrespective of the consistency in the trend of the burden of GI cancers among working-age population and the general population in China, it is not in line with that for the overall global population[4]. This may be due to that the predominant GI cancer types differ between China and other countries[9]. Stomach and liver cancers have remained the most burdensome types of GI cancers in Chinese people over the past 30 years[9]. In contrast, during the same period, the proportion of stomach cancer to all GI cancers continued to decline globally, while colon and rectal cancers have emerged as the most prevalent type of GI cancer worldwide[9].

Moreover, the burden patterns of the six specific GI cancers were not consistent with each other among the working-age population in China. Over the past three decades, the ASIR, ASMR, and ASDR have been increasing for colon/rectum cancer and pancreatic cancer, but decreasing for esophageal cancer, liver cancer, and stomach cancer, and were relatively stable for gallbladder and biliary tract cancer among the participants in this study. This can be explained in three ways. First, with continuous economic development since the late 1970s, lifestyle- and behavior-related risk factors of colon/rectal cancer and pancreatic cancer have been becoming prevalent among Chinese people[21,26], which may applaud the increasing trends in the burden of these two specific GI cancers in China. Second, early screening of esophageal and stomach cancers through endoscopic inspection has been easily accessible for local residents, even at community health service centers in China, resulting in early identification of and timely treatment for potential patients[27]. This may, at least partially, explain the declining trend in the burden of these two cancers. Third, the free and compulsory use of the hepatitis B vaccine since the 1980s has dramatically reduced the incidence of hepatitis B among Chinese people and consequently maintained the prevalence of the disease at a very low level in China[28], which may explain the declining trend in liver cancer in China.

In this study, a significant disparity in the burden of GI cancers was examined between men and women in the Chinese working population. A heavier burden of GI cancers was consistently observed in men than in women, irrespective of the cancer type. Furthermore, the difference in GI cancer burden between men and women became increasingly substantial over time. This may be explained by the fact that GI cancer-related risk factors (including high social stress, occupational risk, smoking, and excessive alcohol consumption) are more prevalent in working-age men than in women in China[29-31].

Additionally, inequality regarding the burden of GI cancer was identified in participants within different age groups over the past 30 years. Compared to the percentages of incidence, mortality, and DALYs in older participants, each of them was higher among their younger counterparts for colon/rectum cancer and liver cancer but lower for esophageal cancer, gallbladder and biliary tract cancer, pancreatic cancer, and stomach cancer. This disparity may be due to differences in the prevalence of lifestyle- and behavior-related risk factors between younger and older people in China over the past decades[21,32]. Excess body weight and lack of physical activity have become increasingly prevalent among younger people[21], whereas alcohol consumption and tobacco use are more common among older residents[32]. Therefore, it shall be a priority to reinforce public health policies focusing on lifestyle and behavioral modifications, including healthy eating, reducing tobacco and alcohol use, and encouraging sufficient physical activity for effective GI cancer prevention, as these may mitigate the risk factors associated with GI cancers.

This study has important public health implications for population-based precision prevention of GI cancers among working-age individuals in China. Although a declining trend was observed in the burden of GI cancers, the total burden of GI cancers remained heavy, and an age and sex disparity in the burden of GI cancers existed in the working-age population from 1990 to 1999 in China. Considering that people at working age are the workforce for a community and play key roles in their families, the loss of or reduction in labor capacity will lead to undesired consequences for the community and, particularly, their own families. Thus, it is critically important to initiate community-based precision intervention programs on GI cancers through age-, sex-, and type-specific, effective, and accessible approaches among the working-age population in China.

As the first study to assess the burden of GI cancers in the working population in China and worldwide, this study has several strengths. First, the participants were the national-level working-age population, who were the social workforce with a strong economic impact on society and, especially, their families. Their health conditions are vital for society and their families. Second, the burdens of all types of GI cancer were analyzed in total and separately over the past three decades. Third, trends in the burden of GI cancer from 1990 to 2019 were examined for the participants, in addition to the burden in 1990 and 2019. Finally, the age and sex disparities in the burden of GI cancer were assessed.

However, some limitations are also worth being mentioned. First, data used in this study were derived from GBD 2019 study, thus the bias in GBD study on estimating the incidence, mortality and DALYs of selected diseases also existed for our study[33]. Second, because province/municipality- and urban-rural level data were not available from the GBD study, only the national-level burdens of GI cancer were assessed. Third, the screening and diagnostic technology of GI cancers was always under the way of evolution over the three decades, which might have resulted in the identification probability increasing over time.

CONCLUSION

The total burden of GI cancers remained heavy among the working-age population in China from 1999 to 2019, although declining trends in the burden of GI cancers were observed over the three decades. Substantial disparities in the burden of GI cancers exist between genders, age groups, and cancer types. From a public health perspective, this study has important implications in that population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals with consideration of age, sex, and cancer type disparity in China.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Oncology

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade C

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Cheng TH S-Editor: Wang JJ L-Editor: A P-Editor: Zhao S

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