Risk Of Digestive Tract Cancers Research Articles

Prebiotics and the Risk of Upper Digestive Tract and Stomach Cancers: The PrebiotiCa Study.

Fiber intake may lower digestive tract cancer risk, possibly by modulating the composition of gut microbiota. However, no data are available about the role of specific fiber fractions with prebiotic activity (e.g., inulin-type fructans (ITFs), fructo-oligosaccharides (FOSs) and galactooligosaccharides (GOSs)) on the risk lower digestive tract cancers. The objective was to assess the association between prebiotic intake and the risk of cancers of the upper digestive tract and stomach. Within the PrebiotiCa study, data were derived from a network of Italian case-control studies conducted between 1992 and 2009. Participants' usual diet was assessed using a food frequency questionnaire. ITFs, and selected FOSs (nystose, kestose, and 1F-β-fructofuranosylnystose) and GOSs (raffinose and stachyose) were quantified in several food products via laboratory analyses. Participants' prebiotic intake was calculated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. Cases were patients admitted to major hospitals with incident histologically confirmed cancers; there were 946 cases of cancer of the oral cavity/pharynx, 198 of the nasopharynx, 304 of the esophagus, 230 of the stomach. More than 4,000 patients admitted to the same hospitals for acute nonneoplastic and not diet-related conditions were selected as control subjects. The outcomes were oral and pharyngeal, nasopharyngeal, esophageal, and stomach cancers. The odds ratios and corresponding 95% CIs of the various cancers were derived using logistic regression models adjusted for major confounders and energy intake. No association was observed between intake of prebiotics and risk of cancers of the oral cavity and pharynx, nasopharynx, and esophagus. High raffinose intake reduced stomach cancer risk (odds ratio for the third vs the first tertile 0.6, 95% CI 0.3 to 0.9); no other prebiotic was associated with stomach cancer. The current study does not support a major role of prebiotic fibers on selected upper digestive tract cancers. The association between high raffinose intake and reduced stomach cancer risk needs further investigation.

Aldehyde dehydrogenase 2 gene rs671 G>A polymorphism is associated with an increased risk of digestive tract cancer.

Acetaldehyde can accumulate in cells and form acetaldehyde-DNA adducts that result in digestive tract cancer development. Acetaldehyde dehydrogenase 2 (ALDH2) enzymatic activity is involved in this process. Here, we aimed to analyze the relationship between an ALDH2 gene polymorphism and the digestive tract cancer risk in the Hakka population in China. This was a retrospective study, with the ALDH2 rs671 genotype and medical record information collected from all subjects. The relationships between these factors, including various blood cell parameters, and digestive tract cancer susceptibility were analyzed. Overall, 307 cancer patients and 317 controls were included. The cancer patients had significantly higher percentages with a history of smoking and drinking alcohol, as well as an increased platelet to lymphocyte ratio and lower lymphocyte to monocyte ratio, compared with the controls. The ALDH2 rs671 genotype and allele distributions were significantly different between the cancer patients and controls. Logistic regression analysis showed that the ALDH2 G/A genotype (G/A vs. G/G) and A/A genotype (A/A vs. G/G) in the co-dominant mode were risk factors for digestive tract cancer susceptibility. ALDH2 rs671 G/A or A/A genotype carriers may have an increased risk of developing digestive tract cancers among the Hakka people.

Increased Risk of Young-Onset Digestive Tract Cancers Among Young Adults Age 20-39 Years With Nonalcoholic Fatty Liver Disease: A Nationwide Cohort Study.

Although the incidence of young-onset digestive tract cancers is increasing worldwide, their risk factors remain largely unknown. We investigated the association between nonalcoholic fatty liver disease (NAFLD) and young-onset digestive tract cancers. This nationwide cohort study included 5,265,590 individuals age 20-39 years who underwent national health screening under the Korean National Health Insurance Service between 2009 and 2012. The fatty liver index was used as a diagnostic biomarker for NAFLD. The participants were followed up until December 2018 to determine the incidence of young-onset digestive tract cancers (ie, esophageal, stomach, colorectal, liver, pancreatic, biliary tract, and gallbladder). Multivariable Cox proportional hazards models were conducted to estimate the risk after adjusting for potential confounders. During the 38.8 million person-years of follow-up, 14,565 patients were newly diagnosed with young-onset digestive tract cancers. The cumulative incidence probability of each cancer type was consistently higher in individuals with NAFLD than in those without NAFLD (all log-rank P < .05). NAFLD was associated with an increased risk of overall digestive tract (adjusted hazard ratio [aHR], 1.16; 95% CI, 1.10 to 1.22), stomach (aHR, 1.14; 95% CI, 1.06 to 1.24), colorectal (aHR, 1.14; 95% CI, 1.06 to 1.22), liver (aHR, 1.13; 95% CI, 1.12 to 1.52), pancreatic (aHR, 1.23; 95% CI, 1.09 to 1.40), biliary tract (aHR, 1.29; 95% CI, 1.00 to 1.66), and gallbladder (aHR, 1.53; 95% CI, 1.01 to 2.31) cancer. These associations remained significant regardless of age, sex, smoking status, alcohol consumption, and obesity status (all P < .05; P for interaction >.05). The aHR for esophageal cancer was 1.67 (95% CI, 0.92 to 3.03). NAFLD may be an independent, modifiable risk factor for young-onset digestive tract cancers. Our findings suggest a crucial opportunity to reduce premature morbidity and mortality associated with young-onset digestive tract cancers in the next generation.

A154 CANCERS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE IN CANADA: A POPULATION-BASED ANALYSIS OF CASES AND MATCHED CONTROLS

Abstract Background Individuals with inflammatory bowel disease (IBD) are known to have a higher risk of digestive tract cancers and cancers associated with immunosuppression. As the IBD population is ageing, age-related cancers may be more commonly diagnosed. Purpose To assess whether IBD patients were at a higher odds of incident cancers than their matched controls stratified by age above and below 65 years. Method A population-based surveillance study was conducted in Alberta, Canada (April 1, 2002 to March 30, 2018). A validated algorithm identified cases of IBD. Each case was age and sex matched to up to 10 non-IBD cases from the general population and linked to the Alberta provincial cancer registry to extract pathology-confirmed incident cancer. Controls were removed if they were not residents of Alberta at the time the matched case was diagnosed with IBD. Only incident cancers diagnosed after the diagnosis of IBD (or matched indexed date for controls) were considered. Age was calculated based on year of inclusion in the cohort or, if applicable, the year of cancer diagnosis. Cancer diagnoses were classified: bladder, biliary and liver, breast, cervix, colorectal, endometrium, gastrointestinal, gynecological, head and neck, hematological, kidney, lung, melanoma, neurological, non-melanoma, pancreas, prostate, renal and bladder, small intestine, thyroid, and miscellaneous. Odds ratios (OR), with 95% confidence intervals (CI), compared IBD cases to matched controls using conditional logistic regression. Stratified analysis at age 65 (&amp;lt;65 and ≥65) was done for all cancers. Result(s) Overall, 3695 incident cancers were diagnosed among 35,763 individuals with IBD as compared to 22,687 cancers among 289,212 controls (OR:1.12; 95%CI: 1.08, 1.16). Those less than 65 years old were at higher odds of developing cancer (1.20; 95%CI: 1.15, 1.26) than those ≥65 (0.97; 95%CI: 0.90, 1.04). Those with IBD had a higher odds biliary and liver (7.41; 95%CI: 5.58, 9.84) and gastrointestinal (2.26; 95%CI: 2.06, 2.48), which including: colorectal (1.78; 95%CI: 1.57, 2.02), pancreas (7.79; 95%CI: 5.53, 10.97), and small intestine (6.59; 95%CI: 4.65, 9.35). Melanoma and non-melanoma, head and neck, and thyroid cancers did not have an increased odds but hematological, lung, neurological, and kidney cancers did show an increased odds among those with IBD. Cancers outside of the gastrointestinal tract were at a lower odds for IBD patients, including: bladder (0.68; 95%CI: 0.54, 0.87), breast (0.72; 95%CI: 0.64, 0.81), gynecological (incl. cervix (0.68; 95%CI: 0.61, 0.78) and endometrium (0.48; 95%CI: 0.34, 0.66), and prostate (0.64; 95%CI: 0.57, 0.73). Image Conclusion(s) Under the age of 65, individuals with IBD have a higher odds of being diagnosed with cancer than the general population, with cancers of the digestive tract driving this association across the age spectrum. Healthcare providers should be aware of higher occurrence of hematological, neurological, lung and renal cancers in those with IBD. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest S. Coward: None Declared, S. Murthy: None Declared, H. Singh Consultant of: Pendopharm, Amgen Canada, Bristol Myers Squibb Canada, Roche Canada, Sandoz Canada, Takeda Canada, and Guardant Health, Inc., E. Benchimol Consultant of: Hoffman La-Roche Limited and Peabody &amp; Arnold LLP for matters unrelated to medications used to treat inflammatory bowel disease and McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat inflammatory bowel disease., E. Kuenzig: None Declared, G. Kaplan Grant / Research support from: Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire, Consultant of: Gilead, Speakers bureau of: AbbVie, Janssen, Pfizer, Amgen, and Takeda

Processed meat, red meat, white meat, and digestive tract cancers: A two-sample Mendelian randomization study.

Previous observational studies suggested inconsistent insights on the associations between meat intake and the risk of digestive tract cancers (DCTs). The causal effect of meat intake on DCTs is unclear. Two-sample Mendelian randomization (MR) was performed based on genome-wide association studies (GWAS) summary data from UK Biobank and FinnGen to evaluate the causal effect of meat intake [processed meat, red meat (pork, beef, and lamb), and white meat (poultry)] on DCTs (esophageal, stomach, liver, biliary tract, pancreatic, and colorectal cancers). The causal effects were estimated using a primary analysis that employed inverse-variance weighting (IVW) and complementary analysis that utilized MR-Egger weighted by the median. A sensitivity analysis was conducted using the Cochran Q statistic, a funnel plot, the MR-Egger intercept, and a leave-one-out approach. MR-PRESSO and Radial MR were performed to identify and remove outliers. To demonstrate direct causal effects, multivariable MR (MVMR) was applied. In addition, risk factors were introduced to explore potential mediators of the relationship between exposure and outcome. The results of the univariable MR analysis indicated that genetically proxied processed meat intake was associated with an increased risk of colorectal cancer [IVW: odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.07-4.19; P = 0.031]. The causal effect is consistent in MVMR (OR = 3.85, 95% CI 1.14-13.04; P = 0.030) after controlling for the influence of other types of exposure. The body mass index and total cholesterol did not mediate the causal effects described above. There was no evidence to support the causal effects of processed meat intake on other cancers, except for colorectal cancer. Similarly, there is no causal association between red meat, white meat intake, and DCTs. Our study reported that processed meat intake increases the risk of colorectal cancer rather than other DCTs. No causal relationship was observed between red and white meat intake and DCTs.

S45 Cancers Associated With Inflammatory Bowel Disease: A Population-Based Case-Control Study

Background: Individuals with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are known to have a higher risk of digestive tract cancers as compared to the general population. As the IBD population has gotten older over time, age-related cancers may be more commonly diagnosed. We conducted a population-based study to assess whether incident cancers were being diagnosed more commonly overtime and whether those with IBD were more likely to be diagnosed with cancer. Methods: A population-based surveillance case-control study was conducted in in Alberta, Canada from April 1, 2002 to March 31, 2018. A validated coding algorithm identified all cases of IBD stratified by type of IBD (CD, UC). Each case was age and sex matched to 10 non-IBD cases from the general population, and then linked to the Alberta provincial cancer registry to extract pathology-confirmed incident cancer. Cancer diagnoses were classified: colorectal, small bowel, pancreatic, biliary and liver, breast, cervical, endometrial, thyroid, hematological, lung, neurological, melanoma, non-melanoma skin cancer, prostate, renal, and bladder. Odds ratios (OR), with 95% confidence intervals (CI), compared IBD cases to matched controls using conditional logistic regression. The annual incidence of cancer diagnosis among the at-risk prevalent IBD population was determined with the average annual percentage change (AAPC) calculated using log binomial regression. Results: Overall, 3,695 incident cancers were diagnosed among 35,763 individuals with IBD as compared to 31,365 cancers among 362,248 controls (IBD: OR = 1.22; 95% CI: 1.18, 1.27; CD: OR = 1.42, 95% CI: 1.34, 1.49; UC: OR = 1.13 95% CI: 1.06, 1.20). Annual incident cancers in those with IBD steadily increased by 3.4% per year (AAPC = 3.44%; 95% CI: 2.71%, 4.18%). A higher odds of cancer was observed across digestive tract cancers for those with IBD: biliary and liver (IBD: OR = 7.76; 95% CI: 5.89, 10.22); colorectal cancer (IBD: OR = 1.88; 95% CI: 1.67, 2.15); small bowel (CD: OR = 10.81; 95% CI: 6.89, 16.95; UC: OR = 1.74; 0.73, 4.16); and pancreas (IBD: OR = 8.01; 95% CI: 5.72, 11.20). Outside of the digestive tract the following cancers were more common in those in IBD: hematological (IBD: OR = 1.47, 95% CI: 1.29, 1.67); lung (IBD: OR = 4.16; 95% CI: 3.59, 4.81); neurological (IBD: OR = 4.73; 95% CI: 3.12, 7.18; and renal (IBD: OR = 2.18; 95% CI: 1.77, 2.68). Non-melanoma skin cancers were associated with IBD (OR = 1.11; 95% CI: 1.05, 1.18), but not melanoma (OR = 0.98; 95% CI: 0.82, 1.18). Other solid-organ cancers were not associated or occurred less commonly in those with IBD: prostate (OR = 0.68; 95% CI: 0.60, 0.77); bladder (OR = 0.73; 95% CI: 0.57, 0.92), cervix (OR = 0.83; 95% CI: 0.73, 0.93), endometrium (OR = 0.50; 95% CI: 0.36, 0.70), and thyroid (OR = 0.84; 95% CI: 0.65, 1.10). Conclusion(s): Over time, persons with IBD are being more commonly diagnosed with cancer. Individuals with IBD are more likely to be diagnosed with cancer as compared to the general population with cancers of the digestive tract driving this association. Healthcare providers should be aware of higher occurrence of hematological, neurological, lung and renal cancers in those with IBD.

Canned Fish Consumption and Upper Digestive Tract Cancers

Canned fish is a widely consumed and affordable food whose effect on cancer risk has been little investigated. We studied its effect on risk of upper digestive tract cancers using data from a network of hospital-based case-control studies from Northern Italy providing information about canned fish consumption as a separate item and including a total of 946 patients with oral cavity and pharynx cancer, 304 patients with esophageal cancer, 230 patients with gastric cancer and 3273 controls. Twenty-three percent of patients with cancer of the oral cavity or pharynx and 26% of those with cancer of the stomach consumed ≥1 serving per week of canned fish, compared to 40% and 49% of the respective control group. Among cases of esophageal cancer and controls 22% consumed ≥1 serving per week of canned fish. Odds ratios for ≥1 vs <1 portion per week were 0.79 (95% Confidence Interval, CI: 0.64–0.97) for cancer of the oral cavity and pharynx, and 0.59 (95% CI: 0.41–0.86) for stomach cancer, whereas there was no inverse association with esophageal cancer. These findings suggest a favorable role of canned fish for selected upper digestive tract cancers.

The Association of Waist Circumference with the Prevalence and Survival of Digestive Tract Cancer in US Adults: A Population Study Based on Machine Learning Methods.

Aims This paper aims to investigate the relationship of waist circumference (WC) with digestive tract cancer morbidity and mortality. Methods Based on the data from a nationally representative US population survey, we summarized the prevalence of digestive tract cancer and all-cause mortality of cancer patients across WC quartiles. Adjusted logistic regression and restricted spline curve were used to analyze WC and the prevalence of digestive tract cancer. Moreover, Cox regression and the Kaplan-Meier curve were applied to investigate the association of WC with all-cause mortality. We also attempted to make a model to predict cancer happening. Results This paper included a total of 34,041 participants, with digestive tract cancer observed in 265 (0.7%) individuals. WC was positively associated with digestive tract cancer morbidity after full adjustment of covariates (OR: 1.72 and 95% CI: 1.41-2.10). Also, individuals in the highest WC group had a higher risk of digestive tract cancer (Q4, OR: 2.71 and 95% CI: 1.48-5.00). Moreover, no significant association was observed in upper digestive cancer, and WC was associated with a longer survival time once diagnosed (hazard ratio (HR): 0.50 and 95% CI: 0.28-0.92). Finally, the model we made proved to be effective. Conclusion High WC is a risk factor for digestive tract cancer with or without adjusting for body mass index, especially those located in the lower digestive tract. However, once digestive tract cancer has been diagnosed, patients with higher WC showed better survival outcomes. Moreover, machine learning methods can be used to predict digestive tract cancer risk in the future.

Morning chronotype and digestive tract cancers: Mendelian randomization study.

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10-8 ) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.

Zinc Intakes and Health Outcomes: An Umbrella Review.

It is widely accepted that the zinc element is crucial in human beings. Zinc has gained more attention during the COVID-19 pandemic due to its utilization for the treatment and prevention of respiratory tract infections. However, some studies also pointed out that zinc intake might cause unwanted side effects and even be dangerous when overdosed. To reveal the relationship between zinc intake and health outcomes, we performed an umbrella review from human studies. In total, the umbrella review included 43 articles and identified 11 outcomes for dietary zinc intake and 86 outcomes for supplementary zinc intake. Dietary zinc intake in the highest dose would decrease the risk of overall and specific digestive tract cancers, depression, and type 2 diabetes mellitus (T2DM) in adults. Supplementary zinc consumption in adults was linked to an improvement of depression, antioxidant capacity and sperm quality, higher serum zinc concentration, and lower concentration of inflammatory markers. Zinc supplementation in children would reduce the incidence of diarrhea and pneumonia, improve zinc deficiency and boost growth. However, zinc might not decrease all-cause mortality in adults or the in-hospital mortality of COVID-19. And better maternal and neonatal outcomes may not derive from pregnant women who consumed higher or lower doses of zinc supplementation (>20 mg/day and <20 mg/day, respectively). Dose-response analyses revealed that a daily 5 mg increment of zinc would lower the risk of colorectal and esophageal cancer, whereas a large dose of zinc supplementation (daily 100 mg) showed no benefit in reducing prostate cancer risk.

S1446 An Unfounded Concern - Proton Pump Inhibitors and Risk of Digestive Tract Cancers: A Systemic Review and Meta-Analysis

S1446 An Unfounded Concern - Proton Pump Inhibitors and Risk of Digestive Tract Cancers: A Systemic Review and Meta-Analysis

Comprehensive analysis of proton pump inhibitors and risk of digestive tract cancers

BackgroundFor the past two decades, dispute on whether proton pump inhibitor (PPI) leads to digestive tract cancer remains, and emerging studies in recent years still demonstrate inconsistent results, which continues to perpetuate concerns over the safety of PPI use. We performed a systematic review and meta-analysis, with comprehensive evaluation by Bradford Hill criteria of causation, to assess the effect of PPI use on digestive tract cancers. MethodsMedline, Embase and Web of Science databases were searched for observational studies published up to 15th January 2021. Pooled relative risks (RRs) were estimated via random effects models. Cumulative defined daily dose- and duration-risk relationships using restricted cubic spline and fractional polynomial models were investigated. Bradford Hill criteria were applied to evaluate causation. PROSPERO Registration: CRD42020211103. ResultsThirty-two publications containing 4,355,254 participants were included. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval (CI) 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% CI 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% CI 1.05 to 2.82) and liver cancer (RR = 1.62, 95% CI 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% CI 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% CI 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. When cumulative defined daily dose or duration increases, the risks decline and become non-significant. Evaluation by Bradford Hill criteria indicates weak evidence of causation. ConclusionsA causal relationship between PPI use and digestive tract cancers is not supported by the evidence in the current review. Concerns over carcinogenic side-effects of PPI might be unfounded.

Epidemiological characteristics of cancers in patients with end-stage kidney disease: a Korean nationwide study

Patients with end-stage kidney disease (ESKD) have been reported to have an increased risk of cancer. However, the epidemiological characteristics of cancer in ESKD patients remain unclear. Therefore, this study aimed to investigate the epidemiological characteristics of cancer in ESKD patients and the differences based on the renal replacement therapy provided. Data on ESKD patients were obtained from the South Korean nationwide cohort Health Insurance Review and Assessment Service database. This study included 58,831 eligible patients of the total 813,907 patients diagnosed with ESKD between January 1, 2007 and December 31, 2017. Of the 58,831 ESKD patients, 3292 (5.6%) were newly diagnosed with cancer. The average duration between the diagnosis of ESKD and cancer was 3.3 ± 1.9 years (mean ± standard deviation), with no differences between hemodialysis, peritoneal dialysis, and kidney transplant groups. The most commonly observed cancer sites in ESKD patients were the colorectum, lung, and liver. The incidence of cancer increased progressively among patients undergoing kidney transplant, peritoneal dialysis, and hemodialysis in that order. Hemodialysis patients were found to have an increased risk of digestive tract cancer compared with kidney transplant patients (adjusted hazard ratio = 1.9; 95% confidence interval: 1.31–2.81; P < 0.001). The study findings may be a useful reference for cancer-screening guidelines.

Association between Socioeconomic Status and Digestive Tract Cancers: A Case-Control Study.

Simple SummaryAn association between socioeconomic status (SES) and cancer risk has been reported, but little is known in Asia. We revealed an association between SES, including education level and areal deprivation index (ADI), and digestive tract cancers in Japan. Lower SES was associated with an increased risk of digestive cancers. For stomach cancer, the positive association with ADI disappeared following an additional adjustment of Helicobacter pylori infection and/or atrophic gastritis status. Cancer prevention policy should consider both individual and regional perspectives by the integration of SES in the target population.Although socioeconomic status (SES) has been associated with cancer risk, little research on this association has been done in Japan. To evaluate the association between SES and digestive tract cancer risk, we conducted a case-control study for head and neck, esophageal, stomach, and colorectal cancers in 3188 cases and the same number of age- and sex-matched controls within the framework of the Hospital-based Epidemiological Research Program at Aichi Cancer Center III (HERPACC III). We employed the education level and areal deprivation index (ADI) as SES indicators. The association was evaluated with odds ratios (ORs) and 95% confidence intervals (CIs) by conditional logistic models adjusted for potential confounders. Even after allowance for known cancer risk factors, the education level showed linear inverse associations with head and neck, stomach, and colorectal cancers. Compared to those educated to junior high school, those with higher education showed statistically significantly lower risks of cancer (0.43 (95% CI: 0.27–0.68) for head and neck, 0.52 (0.38–0.69) for stomach, and 0.52 (0.38–0.71) for colorectum). Consistent with these results for the educational level, the ADI in quintiles showed positive associations with head and neck, esophageal, and stomach cancers (p-trend: p = 0.035 for head and neck, p = 0.02 for esophagus, and p = 0.013 for stomach). Interestingly, the positive association between ADI and stomach cancer risk disappeared in the additional adjustment for Helicobacter pylori infection and/or atrophic gastritis status. In conclusion, a lower SES was associated with an increased risk of digestive cancers in Japan and should be considered in cancer prevention policies for the target population.

External Airborne-agent Exposure Increase Risk of Digestive Tract Cancer

Previous studies have suggested that in addition to respiratory system cancers, exposure to external airborne agents (EAAs) may also affect the risk of digestive tract cancer. However, previous epidemiological studies have been limited. To clarify this relationship, we conducted a Workers’ Korea National Health Insurance Service cohort study. The EAA exposure group comprised participants who had ever visited a hospital as an inpatient for ‘lung diseases due to external agents’. The reference population comprised men from the general working population. The EAA exposure group and reference group included a total of 98,666 and 79,959,286 person-years, respectively. Age-adjusted standardized incident rates (SIRs) with 95% confidence intervals (95%CI) were calculated for each 5-year age stratum. The SIR (95% CI) of EAA exposure was 1.30 (1.19–1.38) for all digestive tract cancers. The highest risk associated with EAA exposure was observed for oral cancer, followed by esophageal and stomach cancers [SIRs (95%CI): 3.96 (3.02–4.78), 3.47(2.60–4.25), and 1.34(1.17–1.47), respectively.] These statistically significant associations did not be attenuated in a subgroup analysis using logistic regression adjusted for age, smoking and alcohol consumption. Our findings suggest that EAA exposure should address risk reduction of both digestive tract and respiratory system cancers.

Across-Site Differences in the Mechanism of Alcohol-Induced Digestive Tract Carcinogenesis: An Evaluation by Mediation Analysis.

A genetic variant on aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the ALDH2 Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior). Alcohol was associated with an increased risk of most digestive tract cancers, but significant direct effects were observed only for upper gastrointestinal tract cancer risk, and varied substantially by site, with ORs (95% confidence interval) of 1.83 (1.43-2.36) for head and neck cancer, 21.15 (9.11-49.12) for esophageal cancer, and 1.65 (1.38-1.96) for stomach cancer. In contrast, a significant protective indirect effect was observed on risk for all cancers, except small intestine cancer. These findings suggest that alcohol is a major risk factor for digestive tract cancers, but its impact as a surrogate for acetaldehyde exposure appears heterogeneous by site. Meanwhile, the behavior-related effect of the ALDH2 Lys allele results in a decreased risk of most digestive tract cancers. SIGNIFICANCE: These findings support that genetic alcohol avoidance is a factor against alcohol-induced cancers.

Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 (CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 (CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1. The glutathione S-transferase mu 1 (GSTM1) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

Prediction of Metabolic Syndrome for the Survival of Patients With Digestive Tract Cancer: A Meta-Analysis.

Background and Objectives: Growing evidence indicates that metabolic syndrome confers a differential risk for the development and progression of many types of cancer, especially in the digestive tract system. We here synthesized the results of published cohort studies to test whether baseline metabolic syndrome and its components can predict survival in patients with esophageal, gastric, or colorectal cancer.Methods: Literature retrieval, publication selection and data extraction were performed independently by two authors. Analyses were done using STATA software (version 14.1).Results: A total of 15 publications involving 54,656 patients were meta-analyzed. In overall analyses, the presence of metabolic syndrome was associated with a non-significant 19% increased mortality risk for digestive tract cancer (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.45 to 2.520.95 to 1.49, P = 0.130; I2: 94.8%). In stratified analyses, the association between metabolic syndrome and digestive tract cancer survival was statistically significant in prospective studies (HR: 1.64, 95% CI: 1.18 to 2.28), in studies involving postsurgical patients (HR: 1.42, 95% CI: 1.06 to 1.92), and in studies assessing cancer-specific survival (HR: 1.91, 95% CI: 1.45 to 2.52). Further meta-regression analyses indicated that age and smoking were potential sources of between-study heterogeneity (both P < 0.001). The shape of the Begg's funnel plot seemed symmetrical (Begg's test P = 0.945 and Egger's test P = 0.305).Conclusions: Our findings indicate that metabolic syndrome is associated with an increased risk of postsurgical digestive tract cancer-specific mortality. Continued investigations are needed to uncover the precise molecule mechanism linking metabolic syndrome and digestive tract cancer.

Homocysteine and Digestive Tract Cancer Risk: A Dose-Response Meta-Analysis.

Background Homocysteine, a key component in one-carbon metabolism, is of great importance in remethylation. Many epidemiologic studies have assessed the association between homocysteine and risk of digestive tract cancer, but the results are inconsistent. Objective The objective of our meta-analysis is to assess the association between homocysteine and digestive tract cancer risk. Methods Comprehensive searches were performed on the PubMed, Embase, Cochrane, and Web of Science databases up to September 25, 2018, to identify relevant studies. Thirteen studies were included in the meta-analysis. Odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were used to estimate the strength of the relationship between homocysteine and the risk of digestive tract cancer. Results The pooled OR of digestive tract cancer risk for patients with the highest categories of blood homocysteine levels versus the lowest categories was 1.27 (95% CI, 1.15, 1.39) with no significant heterogeneity observed (P = 0.798, I2 = 0.0%). Moreover, the dose-response analysis revealed that each 5μmol/L increase in homocysteine increased the incidence of digestive tract cancer by 7%. Conclusion Generally, our results indicated that elevated homocysteine was associated with higher risk of digestive tract cancer. That is, homocysteine concentration may be a potential biomarker for occurrence of digestive tract cancer.

A meta-analysis of caspase-8 -652 6N del polymorphism and digestive tract cancer risk

Caspase-8 (CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism (-652 6N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk. To evaluate the association between the CASP8 -652 6N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model (del/del vs. ins/ins: OR= 0.82, 95%CI= 0.72–0.95; del/ins vs. ins/ins: OR= 0.92, 95%CI= 0.87–0.97; dominant model (del/ins+ del/del vs. ins/ins: OR= 0.91, 95%CI= 0.87–0.96, recessive model: del/del vs. del/ins+ ins/ins: OR= 0.85, 95%CI= 0.75–0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models, except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8 -652 6N del polymorphism and reduced digestive cancer risk, especially among Asians and population-based studies.