Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk

Ri Cui, Yoichiro Kamatani, Atsushi Takahashi, Masayuki Usami, Naoya Hosono, Takahisa Kawaguchi, Tatsuhiko Tsunoda, Naoyuki Kamatani, Michiaki Kubo, Yusuke Nakamura, Koichi Matsuda

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Esophageal squamous cell carcinoma (ESCC) is prevalent among Asian populations, with marked regional variations in incidence and mortality. Patients with ESCC have a very poor prognosis, but detection of ESCC at earlier stages could improve clinical outcome. Therefore, identification of epidemiologic factors that influence the development of ESCC would facilitate prevention and/or early detection of the disease. Methods: We performed a 2-step genome-wide association study with subsequent replication analysis using a total of 1070 Japanese ESCC cases and 2836 controls. We also used logistic regression analysis to estimate the effect of gene-gene and gene-environmental interactions. Results: We identified the significant associations of ESCC with 4q21-23 and 12q24 regions, which include nonsynonymous single nucleotide polymorphisms (SNP) in ADH1B (rs1229984, P = 6.76 × 10-35) and ALDH2 (rs671, P = 3.68 × 10-68) that were previously shown to be associated with ESCC susceptibility. Multiple logistic regression analysis revealed SNP rs671, rs1229984, alcohol drinking, and smoking as the independent risk factors for ESCC (odds ratios of 1.66, 1.85, 1.92, and 1.79, respectively). Moreover, individuals who had both genetic and lifestyle-related risk factors had a nearly 190 times higher risk of ESCC than those who had neither of these. Conclusions: We found 2 known functional variants involved in the metabolism of alcohol and tobacco by-products as the most significant risk factors for the development of ESCC in a Japanese population. The individuals carrying both risk genotypes have a higher baseline risk of ESCC that is substantially increased by 2 lifestyle risk factors.

Original languageEnglish
Pages (from-to)1768-1775
Number of pages8
JournalGastroenterology
Volume137
Issue number5
DOIs
Publication statusPublished - 01-01-2009
Externally publishedYes

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Esophageal Neoplasms
Smoking
Alcohols
Single Nucleotide Polymorphism
Life Style
Esophageal Squamous Cell Carcinoma
Logistic Models
Epidemiologic Factors
Regression Analysis
Genes
Genome-Wide Association Study
Tobacco Products
Alcohol Drinking
Population
Early Diagnosis
Odds Ratio
Genotype
Mortality

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Cui, R., Kamatani, Y., Takahashi, A., Usami, M., Hosono, N., Kawaguchi, T., ... Matsuda, K. (2009). Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk. Gastroenterology, 137(5), 1768-1775. https://doi.org/10.1053/j.gastro.2009.07.070
Cui, Ri ; Kamatani, Yoichiro ; Takahashi, Atsushi ; Usami, Masayuki ; Hosono, Naoya ; Kawaguchi, Takahisa ; Tsunoda, Tatsuhiko ; Kamatani, Naoyuki ; Kubo, Michiaki ; Nakamura, Yusuke ; Matsuda, Koichi. / Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk. In: Gastroenterology. 2009 ; Vol. 137, No. 5. pp. 1768-1775.
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Cui, R, Kamatani, Y, Takahashi, A, Usami, M, Hosono, N, Kawaguchi, T, Tsunoda, T, Kamatani, N, Kubo, M, Nakamura, Y & Matsuda, K 2009, 'Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk', Gastroenterology, vol. 137, no. 5, pp. 1768-1775. https://doi.org/10.1053/j.gastro.2009.07.070

Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk. / Cui, Ri; Kamatani, Yoichiro; Takahashi, Atsushi; Usami, Masayuki; Hosono, Naoya; Kawaguchi, Takahisa; Tsunoda, Tatsuhiko; Kamatani, Naoyuki; Kubo, Michiaki; Nakamura, Yusuke; Matsuda, Koichi.

In: Gastroenterology, Vol. 137, No. 5, 01.01.2009, p. 1768-1775.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional Variants in ADH1B and ALDH2 Coupled With Alcohol and Smoking Synergistically Enhance Esophageal Cancer Risk

AU - Cui, Ri

AU - Kamatani, Yoichiro

AU - Takahashi, Atsushi

AU - Usami, Masayuki

AU - Hosono, Naoya

AU - Kawaguchi, Takahisa

AU - Tsunoda, Tatsuhiko

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Matsuda, Koichi

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Background & Aims: Esophageal squamous cell carcinoma (ESCC) is prevalent among Asian populations, with marked regional variations in incidence and mortality. Patients with ESCC have a very poor prognosis, but detection of ESCC at earlier stages could improve clinical outcome. Therefore, identification of epidemiologic factors that influence the development of ESCC would facilitate prevention and/or early detection of the disease. Methods: We performed a 2-step genome-wide association study with subsequent replication analysis using a total of 1070 Japanese ESCC cases and 2836 controls. We also used logistic regression analysis to estimate the effect of gene-gene and gene-environmental interactions. Results: We identified the significant associations of ESCC with 4q21-23 and 12q24 regions, which include nonsynonymous single nucleotide polymorphisms (SNP) in ADH1B (rs1229984, P = 6.76 × 10-35) and ALDH2 (rs671, P = 3.68 × 10-68) that were previously shown to be associated with ESCC susceptibility. Multiple logistic regression analysis revealed SNP rs671, rs1229984, alcohol drinking, and smoking as the independent risk factors for ESCC (odds ratios of 1.66, 1.85, 1.92, and 1.79, respectively). Moreover, individuals who had both genetic and lifestyle-related risk factors had a nearly 190 times higher risk of ESCC than those who had neither of these. Conclusions: We found 2 known functional variants involved in the metabolism of alcohol and tobacco by-products as the most significant risk factors for the development of ESCC in a Japanese population. The individuals carrying both risk genotypes have a higher baseline risk of ESCC that is substantially increased by 2 lifestyle risk factors.

AB - Background & Aims: Esophageal squamous cell carcinoma (ESCC) is prevalent among Asian populations, with marked regional variations in incidence and mortality. Patients with ESCC have a very poor prognosis, but detection of ESCC at earlier stages could improve clinical outcome. Therefore, identification of epidemiologic factors that influence the development of ESCC would facilitate prevention and/or early detection of the disease. Methods: We performed a 2-step genome-wide association study with subsequent replication analysis using a total of 1070 Japanese ESCC cases and 2836 controls. We also used logistic regression analysis to estimate the effect of gene-gene and gene-environmental interactions. Results: We identified the significant associations of ESCC with 4q21-23 and 12q24 regions, which include nonsynonymous single nucleotide polymorphisms (SNP) in ADH1B (rs1229984, P = 6.76 × 10-35) and ALDH2 (rs671, P = 3.68 × 10-68) that were previously shown to be associated with ESCC susceptibility. Multiple logistic regression analysis revealed SNP rs671, rs1229984, alcohol drinking, and smoking as the independent risk factors for ESCC (odds ratios of 1.66, 1.85, 1.92, and 1.79, respectively). Moreover, individuals who had both genetic and lifestyle-related risk factors had a nearly 190 times higher risk of ESCC than those who had neither of these. Conclusions: We found 2 known functional variants involved in the metabolism of alcohol and tobacco by-products as the most significant risk factors for the development of ESCC in a Japanese population. The individuals carrying both risk genotypes have a higher baseline risk of ESCC that is substantially increased by 2 lifestyle risk factors.

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DO - 10.1053/j.gastro.2009.07.070

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JO - Gastroenterology

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