Pre-existing diabetes mellitus increases the risk of gastric cancer: A meta-analysis

Table 1 Characteristics of 15 studies included in the meta-analysis of the gastric cancer risk of preexisting diabetes

Study		Study type	Country	DM criteria	Age (yr)	Follow up (yr)	Least interval1 (yr)	Sex	DM prevalence	RR or OR (95%CI)	Adjustment variables/matched variable of selection	NOS
Atchison et al[53]		CS	United States (veterans)	Registration	18-100	27	1	Male	13.2%	0.95 (0.89-1.02)	Age, time, latency, race, number of visits, diagnoses of alcohol–related conditions, obesity and COPD	8
Carstensen et al[19]		CS	Denmark	Registration	No limit	15	Not mentioned	Male		1.28 (1.15-1.43)	Age, calendar time, date of birth	8
								Female		1.34 (1.14-1.58)
Jiang et al[20]		CC	United States	Self reported	30-74		1	Both		1.51 (1.10-2.07)2	Age, sex, race, education, birth place, smoking and BMI	7 (5)5
Lin et al[22]		CS	United States	Self reported	50-71	10	2	Male	9.9%	1.52 (1.21-1.92)2	Age, calories, alcohol consumption, smoking, fruit consumption, vegetable consumption, ethnicity, education, and physical activity	8 (6)5
								Female	7.2%	1.62 (0.98-2.68)2
Wotton et al[16]	ORLS1	CS	England	Registration	≥ 30	35	0	Both	5.5%	1.11 (0.89-1.37)	Sex, age in 5-year bands, time and district of residence	8
	ORLS2					9			4.0%	2.05 (1.30-3.10)
Chodick et al[54]		CS	Israel	Registration	≥ 21	8	0	Male		1.44 (0.98-2.11)	Age, region, SES level, use of healthcare, BMI, and history of CVD/matched for age, sex	8
								Female		0.99 (0.55-1.80)
Ikeda et al[37]		CS	Japan	HbA1c (5.0%-5.9% vs 7.0%)	≥ 40	14	Not mentioned	Both	3.9%	2.69 (1.24-5.85)	Age, sex, H. pylori, history of peptic ulcer, BMI, TC, alcohol intake, smoking, dietary factor4	8
Ogunleye et al[55]		CS	Scotland	Registration (only type 2 DM)	No limit	11	1	Both		0.77 (0.36-1.66)	Deprivation deciles of Carstairs/matched for age, sex and doctor practice	8
Kuriki et al[29]		CC	Japan	Self reported	40-80		Not mentioned	Male		1.16 (0.93-1.44)	Age, BMI, drinking, smoking, exercise, bowel movement, FHx of cancer and DM, dietary restriction, vegetable intake, greasy food, snack	6
								Female		1.70 (1.16-2.48)
Inoue et al[27]		CS	Japan	Self reported	40-69	13	5	Male	6.7%	1.09 (0.79-1.5)	Age, study area, history of CVD and IHD, smoking, BMI, physical activity, alcohol, vegetable, coffee	9
								Female	3.0%	1.92 (1.06-3.47)
Jun et al[57]		NCC	Korea	FBS (< 99 mg/dL vs≥ 126 mg/dL)	≥ 35	Case 2.4/control 6.5 h	2	Both		1.77 (0.57-5.45)	H. pylori, smoking, drinking, and education level/matched on age, sex, year and area of enrollment, and follow-up duration	9
Khan et al[28]		CS	Japan	Self reported	40-79	19	2	Male	7.5%	0.72 (0.40-1.09)	Age, BMI, smoking, drinking	8
								Female	4.6%	0.26 (0.08-0.82)
Rapp et al[15]		CS	Austria	FBS (4.2-5.2 mmol/L vs 7.0 mmol/L)	> 19	14	1	Male	3.9%	0.84 (0.38-1.87)	Age, smoking, occupation, BMI	8
								Female	3.0%	-3
Rousseau et al[56]		CC	Canada	Self reported	35-70		2	Male		1.0 (0.5-1.8)	Age, income, education, ethnicity, proxy status, BMI, smoking, beta-carotene, alcohol	7
Jee et al[26]		CS	South Korea	FBS (< 90 mg/dL vs≥ 126 mg/dL) or DM medication	30-95	10	1	Male	5.1%	1.11 (1.04-1.2)	Age, age squared, smoking, alcohol	8
								Female	4.5%	1.15 (0.99-1.34)
La Vecchia et al[25]		CC	Italy	Self reported	≤ 75		Not mentioned	Male		0.6 (0.4-1.0)	Age	6
								Female		0.7 (0.4-1.2)
O'Mara et al[21]		CC	USA (only white)	Self reported	30-89		1	Male		0.91 (0.28-2.27)2	Age	4 (3)5
								Female		1.57 (0.48-3.94)

¹Interval between diabetes mellitus (DM) and gastric cancer to be selected as population;

²Calculated from table without adjustment by Fisher’s exact test;

³No estimate was reported due to less than 5 cases in DM patients;

⁴Energy, fat, salt, vitamin, dietary fibers;

⁵The first numbers are Newcastle-Ottawa Quality Assessment Scale (NOS) of original studies. The second numbers in brackets are downgraded NOS because we calculated new estimates without adjustment. Subgroup analysis were done according to the second numbers. CS: Cohort study; CC: Case control study; NCC: Nested case-control study; BMI: Body mass index; FBS: Fasting blood glucose; FHx: Family history; TC: Total cholesterol; CVD: Cardiovascular disease; IHD: Ischemic heart disease; ORLS: Oxford Record Linkage Study; H. pylori: Helicobacter pylori; COPD: Chronic obstructive pulmonary disease.

Table 2 Preexisting diabetes and risk of gastric cancer by subgroup meta-analysis using random effect model

	Studies (n)	RR (95%CI)	I2% (95%CI)
Overall	27	1.19 (1.08-1.31)	70.7 (56.8-80.2)
Countries
East Asian countries1	10	1.19 (1.02-1.38)	60.1 (20.0-80.1)
Western countries2	17	1.18 (1.03-1.36)	75.6 (61.0-84.8)
Study type
Cohort study	18	1.20 (1.08-1.34)	75.5 (61.2-84.5)
Case control study	9	1.12 (0.87-1.45)	57.9 (11.8-79.9)
Sex
Male	12	1.10 (0.97-1.24)	74.9 (55.7-85.8)
Female	9	1.24 (1.01-1.52)	58.9 (14.1-80.3)
DM criteria
Registration	8	1.21 (1.02-1.44)	83.0 (67.8-91.0)
Measured3	5	1.15 (1.01-1.32)	35.5 (0.0-75.8)
Self report	14	1.13 (0.93-1.39)	65.2 (38.6-80.3)
Interval4
One and more years	15	1.15 (1.02-1.31)	67.5 (44.3-81.0)
Quality (NOS)
High quality (8 and more)	17	1.17 (1.05-1.31)	73.4 (57.0-83.6)
Low quality (7 and less)	10	1.20 (0.97-1.49)	61.2 (22.6-80.5)
Adjustment for risk factor
Smoking5	12	1.17 (1.01-1.34)	52.6 (8.7-75.4)
H. pylori5	2	2.35 (1.24-4.46)	0.0 (UC)
Cancer site
Cardia cancer	2	1.39 (0.72-2.69)	82.3 (UC)
Noncardia cancer	2	1.19 (0.80-1.77)	59.6 (UC)

¹Japan, South Korea;

²United States, Canada, Europe and Israel;

³Using fasting blood glucose or HbA1c as criteria;

⁴The least cancer-free time of subject according to study design;

⁵The subgroup of studies designed to include the risk factor as adjustment variables. RR: Relative risk; UC: Unable to calculate due to low degree of freedom; NOS: Newcastle-Ottawa Quality Assessment Scale; H. pylori: Helicobacter pylori.