Explore the influence of family history of upper gastrointestinal (UGI) cancer on UGI cancer death, based on the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort.

Family history of UGI cancer was defined as at least one first-degree relative (parent, child, or sibling) had a history of esophageal or gastric cancer. Cancer death was carried out by ICD-10 code. Family history information was collected at baseline and cancer deaths were assessed at each annual follow-up. The COX proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). We compared the positive family history group with the negative to determine the risk of family history on UGI cancer death. The effect of category of relatives, number of relatives with UGI cancer, and diagnosis age of relatives on the UGI death risk were further analyzed. Interaction and stratification analyses were done to see the subgroup effects. Sensitivity analyses were also conducted by exclusion of individuals who were followed up less than three years. We considered controlling of covariates including: gender, age (continuity), community, education level, number of siblings (continuity), BMI (continuity), smoking, alcohol use, fresh fruit intake, fresh vegetable intake, hot beverage intake, edible oil intake, meat intake, and moldy staple food intake. All food intake variables were converted into categorical variables.

From1985 to2015, we followed up total 3,318 individuals with 898 UGI cancer deaths (537 from ESCC, 77 from GNCC, and 284 from GCC). In a single factor analysis, family history of UGI cancer increased the risk of death of esophageal squamous cell carcinoma (ESCC) by 27% (HR=1.270, 95%CI1.072-1.504). No associations were observed in gastric cardia carcinoma (GCC) and gastric non-cardia carcinoma (GNCC). After adjusting for multi-factor, a family history of UGI cancer risk of death increased by 31.9% from ESCC (HR=1.319,95%CI:1.110-1.567). Subgroup analysis of different types of relatives with UGI cancers, UGI cancers in the mother (HR=1.457,95%CI:1.200-1.768), brother (HR=1.522,95%CI:1.117-2.073), and sister (HR=1.999,95%CI:1.419-2.817) were independent risk factors for ESCC death, while the father was not. In addition, 2 relatives with UGI cancer (HR=1.495, 95%, CI:1.110-2.013) and ≥3 relatives with UGI cancer (HR=2.836, 95%CI:1.842-4.367) significantly increased the risk of ESCC death, and the trend test was statistically significant (P<0.001). Relatives’ diagnostic age of 51-60 years (HR=1.322, 95%CI:1.046-1.672) and 41-50 years (HR=1.442, 95%CI:1.078-1.930) were the risk factors for ESCC death, with statistical significance in the trend test (P=0.010). No statistically significant result of the family history effect on the risk of death from GCC or GNCC was found. Sensitivity analysis of 80% of subjects, randomly selected, did not change the results.

A family history of UGI cancer may predict the risk of death from ESCC but not from GCC or GNCC. UGI cancer in the mother may predict the risk of death from ESCC, but not father, which indicates gender differences. Gender and smoking are the interaction items with family history in a similar extent. In the subgroup, the risk of ESCC death is more distinct by family history in younger, female, and better-lifestyle individuals, which indicates the unique role of genetic factors.

• Linxian Dysplasia Nutrition Intervention Trial
• esophageal squamous dysplasia
• family history
• lifestyle
• upper gastrointestinal cancer

Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions.

We performed an endoscopic examination of 44,857 individuals aged 40–69 years from five high incidence regions of China in 2017–2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors.

We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52–3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03–3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05–1.37) was essential risk factor of LGIN.

Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

The online version contains supplementary material available at 10.1186/s12885-021-08764-x.

• Cross-sectional study
• Esophageal squamous cell carcinoma
• Precancerous lesions
• Prevention
• Risk factor

• CYP2C19
• Global Screening Array
• In silico analysis
• Transcriptional factor binding

• 5-Year cumulative survival
• Buccal mucosa cancer
• CYP2D6*4
• CYP3A5*3
• SULT1A1*2
• Tongue cancer

• Esophageal cancer
• LC-MS/MS
• Nitrosamines exposure
• Risk

• China
• Chromatography, Liquid
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Humans
• Incidence
• Nitrosamines
• Tandem Mass Spectrometry

• China
• endoscopic screening
• esophageal squamous cell carcinoma
• individualized assessment
• risk prediction

• Cancer
• Esophageal
• Incidence
• Iran
• Kurdistan

• Han Chinese population
• MassARRAY system
• esophagi al squamous cell carcinoma (ESCC)
• genome-wide association study (GWAS)
• single nucleotide polymorphism (SNP)

• cytochrome P450 (CYP450)
• genetic polymorphism
• lung cancer
• susceptibility

• Gastrointestinal neoplasm
• Medical history taking
• Risk factors

To investigate the incidence and mortality rates of upper gastrointestinal cancer (UGIC) in Hebei Province, China, and to identify high-risk populations to improve UGIC prevention and control.

Data for UGIC patients were collected from 21 population-based cancer registries covering 15.25% of the population in Hebei Province. Mortality data were extracted from three national retrospective death surveys (1973-1975, 1990-1992 and 2004-2005). The data were stratified by 5-year age groups, gender and area (high-risk/non-high-risk areas) for analysis. The age-period-cohort and grey system model were used.

The crude incidence rate of UGIC was 55.47/100000, and the adjusted rate (Segi’s population) was 44.90/100000. Males in rural areas had the highest incidence rate (world age-standardized rate = 87.89/100000). The crude mortality rate of UGIC displayed a decreasing trend in Hebei Province from the 1970s to 2013, and the adjusted rate decreased by 43.81% from the 1970s (58.07/100000) to 2013 (32.63/100000). The mortality rate declined more significantly in the high-risk areas (57.26%) than in the non-high-risk areas (55.02%) from the 1970s to 2013. The median age at diagnosis of UGIC was 65.06 years in 2013. There was a notable delay in the median age at death from the 1970s (66.15 years) to 2013 (70.39 years), especially in the high-risk areas. In Cixian, the total trend of the cohort effect declined, and people aged 65-69 years were a population at relatively high risk for UGIC. We predicted that the crude mortality rates of UGIC in Cixian and Shexian would decrease to 98.80 and 133.99 per 100000 in 2018, respectively.

UGIC was the major cause of cancer death in Hebei Province, and males in rural areas were a high-risk population. We should strengthen early detection and treatment of UGIC in this population.

• Upper gastrointestinal cancer
• Incidence
• Mortality
• Age-period-cohort
• Grey system model

• Adult
• Age Distribution
• Aged
• Aged, 80 and over
• Cause of Death
• China/epidemiology
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/mortality
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Registries
• Retrospective Studies
• Rural Health
• Sex Distribution
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/mortality
• Time Factors
• Urban Health

• Epidemiology
• Family history
• Gastric cancer
• Genetic polymorphism
• MMP9

• Adolescent
• Anthropometry
• Body Mass Index
• Child
• Cross-Sectional Studies
• Exercise
• Female
• Follow-Up Studies
• Humans
• India/epidemiology
• Male
• Obesity/epidemiology
• Obesity/etiology
• Obesity/prevention & control
• Overweight/complications
• Prevalence
• Risk Factors
• Schools
• Triglycerides/metabolism

The current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC).

A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC.

The 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was.

The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.

• Esophageal squamous cell carcinoma
• Long-term survival
• Prognostic factor

• Esophageal squamous cell carcinoma risk
• Gene-environment interaction
• Kashmir
• Polymorphism
• Xeroderma pigmentosum A and C