Journal Article

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

Guha, Manalee, Bankura, Biswabandhu, Maji, Suvendu, Saha, Makhan Lal, Ghosh, Soumee, Nachimuthu, Senthil Kumar, Panda, Chinmoy Kumar, Ghosh, Sudakshina, Chakraborty, Subrata, Maity, Biswanath, Pattanayak, Arup Kumar, Ghatak, Souvik, Das, Madhusudan

2017

Overview

Background 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 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. Methods We 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. Results Genotype 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). Conclusion In 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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Acetaldehyde / ADH1A / ADH1B / ADH1C / Adult / Aged / Aged, 80 and over / Alcohol Dehydrogenase - genetics / Aldehyde Dehydrogenase, Mitochondrial - genetics / ALDH2 / Alleles / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer genetics / Cancer Research / Case-Control Studies / Diagnosis / DNA sequencing / Enzymes / Female / Gastric cancer / Gene Frequency / Genes / Genetic aspects / Genetic Predisposition to Disease / Genetic research / Genetics / genomics and epigenetics / Genotype / Health aspects / Health Promotion and Disease Prevention / Helicobacter Infections - complications / Helicobacter pylori / Humans / India / Kaplan-Meier Estimate / Linkage Disequilibrium / Male / Medicine/Public Health / Middle Aged / Mortality / Odds Ratio / Oncology / Physiological aspects / Polymorphism, Genetic / Polymorphism, Single Nucleotide / Research Article / Risk / Risk factors / Single nucleotide polymorphisms / Stomach cancer / Stomach Neoplasms - etiology / Stomach Neoplasms - genetics / Surgical Oncology / Young Adult