Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India

Abstract

BackgroundGastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a carcinogenic intermediate of ethanol metabolism contributes to the risk of GC. The accumulation of AA largely depends on the activity of the major metabolic enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This study aimed to evaluate the association between genetic variants in these genes and GC risk in West Bengal, India.MethodsWe enrolled 105 GC patients (cases), and their corresponding sex, age and ethnicity was matched to 108 normal individuals (controls). Genotyping for ADH1A (rs1230025), ADH1B (rs3811802, rs1229982, rs1229984, rs6413413, rs4147536, rs2066702 and rs17033), ADH1C (rs698) and ALDH2 (rs886205, rs968529, rs16941667 and rs671) was performed using DNA sequencing and RFLP.ResultsGenotype and allele frequency analysis of these SNPs revealed that G allele of rs17033 is a risk allele (A vs G: OR = 3.67, 95% CI = 1.54–8.75, p = 0.002) for GC. Significant association was also observed between rs671 and incidence of GC (p = 0.003). Moreover, smokers having the Lys allele of rs671 had a 7-fold increased risk of acquiring the disease (OR = 7.58, 95% CI = 1.34–42.78, p = 0.009).ConclusionIn conclusion, rs17033 of ADH1B and rs671 of ALDH2 SNPs were associated with GC risk and smoking habit may further modify the effect of rs671. Conversely, rs4147536 of ADH1B might have a protective role in our study population. Additional studies with a larger patient population are needed to confirm our results.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3713-7) contains supplementary material, which is available to authorized users.

Association between rs1229984 in ADH1B and cancer prevalence in a Japanese population

“…Analyses of liver, pancreas and colon cancer were presented due to evidence that these are alcohol-related cancers (21). Stomach cancer is presented due to previous investigations into its association with rs229984 (22)(23)(24)(25). Lung cancer is presented due to adequate sample size and significant findings.…”

Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

“…The transformation of ethanol into its carcinogenic metabolite, acetaldehyde, is especially important for the elimination of ADH1 in the liver [ 10 ]. A significant association was found between gastric cancer risk and a common 3′-untranslated region flanking a single-nucleotide polymorphism near rs1230025 of ADH1A [ 11 ]. The most important function-associated polymorphism in ADH is considered to be ADH1B Arg48His (rs1229984) [ 12 ].…”

“…The most important function-associated polymorphism in ADH is considered to be ADH1B Arg48His (rs1229984) [ 12 ]. Rs17033 of ADH1B is related to the risk of gastric cancer and smoking may further affect the role of rs671 [ 11 ]. Positive responses of ADH1B *3 and alcohol dependence have been found in African and Native American populations [ 13 , 14 ].…”

Prognostic Implications of Alcohol Dehydrogenases Inhepatocellular Carcinoma

“…In recent years, large numbers of investigations have reported that gene polymorphism of ADHs was correlated with cancer risk [17,18,[31][32][33]. Moreover, the activity of ADH isoenzymes was signi cantly higher in liver cancer tissues than in healthy tissues [34], suggested the diagnostic value of ADH for the patients with liver cancer.…”