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.
Highlights
Gastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality
We found that individuals carrying both the risk alleles showed 5 fold increased risk (p = 0.013; Odds ratio = 5.66; 95% Confidential Interval (CI): 1.22–26.14) of GC compared to individuals carrying a single or no risk allele
We conducted the first study regarding the associations between ADH1A, ADH1B, ADH1C and ALDH2 genes polymorphisms and the risk of GC from West Bengal, India
Summary
Gastric 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 asymptomatic disease presentation with nonspecific signs and symptoms in its early stage results in relatively poor prognosis due to advanced disease progression and a high mortality rate [1, 2] It is the fourth most common cancer and the third leading cause of global cancer death despite its declining incidence in the recent decade [3]. Due to the critical function of alcohol and aldehyde dehydrogenases in controlling the conversion of alcohol to toxic intermediates, understanding how genetic variants in these genes contribute to GC development could provide new understanding into the role of alcohol consumption in encoding GC risk
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