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

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 majo...

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Autores principales: Ghosh, Sudakshina, Bankura, Biswabandhu, Ghosh, Soumee, Saha, Makhan Lal, Pattanayak, Arup Kumar, Ghatak, Souvik, Guha, Manalee, Nachimuthu, Senthil Kumar, Panda, Chinmoy Kumar, Maji, Suvendu, Chakraborty, Subrata, Maity, Biswanath, Das, Madhusudan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700676/
https://www.ncbi.nlm.nih.gov/pubmed/29166882
http://dx.doi.org/10.1186/s12885-017-3713-7
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author Ghosh, Sudakshina
Bankura, Biswabandhu
Ghosh, Soumee
Saha, Makhan Lal
Pattanayak, Arup Kumar
Ghatak, Souvik
Guha, Manalee
Nachimuthu, Senthil Kumar
Panda, Chinmoy Kumar
Maji, Suvendu
Chakraborty, Subrata
Maity, Biswanath
Das, Madhusudan
author_facet Ghosh, Sudakshina
Bankura, Biswabandhu
Ghosh, Soumee
Saha, Makhan Lal
Pattanayak, Arup Kumar
Ghatak, Souvik
Guha, Manalee
Nachimuthu, Senthil Kumar
Panda, Chinmoy Kumar
Maji, Suvendu
Chakraborty, Subrata
Maity, Biswanath
Das, Madhusudan
author_sort Ghosh, Sudakshina
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3713-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-57006762017-12-01 Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India Ghosh, Sudakshina Bankura, Biswabandhu Ghosh, Soumee Saha, Makhan Lal Pattanayak, Arup Kumar Ghatak, Souvik Guha, Manalee Nachimuthu, Senthil Kumar Panda, Chinmoy Kumar Maji, Suvendu Chakraborty, Subrata Maity, Biswanath Das, Madhusudan BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3713-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-22 /pmc/articles/PMC5700676/ /pubmed/29166882 http://dx.doi.org/10.1186/s12885-017-3713-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ghosh, Sudakshina
Bankura, Biswabandhu
Ghosh, Soumee
Saha, Makhan Lal
Pattanayak, Arup Kumar
Ghatak, Souvik
Guha, Manalee
Nachimuthu, Senthil Kumar
Panda, Chinmoy Kumar
Maji, Suvendu
Chakraborty, Subrata
Maity, Biswanath
Das, Madhusudan
Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title_full Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title_fullStr Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title_full_unstemmed Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title_short Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India
title_sort polymorphisms in adh1b and aldh2 genes associated with the increased risk of gastric cancer in west bengal, india
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700676/
https://www.ncbi.nlm.nih.gov/pubmed/29166882
http://dx.doi.org/10.1186/s12885-017-3713-7
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