Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles

Fumiaki Tanaka, Ken Yamamoto, Sadao Suzuki, Hiroshi Inoue, Masahiko Tsurumaru, Yoshiaki Kajiyama, Hoichi Kato, Hiroyasu Igaki, Koh Furuta, Hiromasa Fujita, Toshiaki Tanaka, Yoichi Tanaka, Yoshiyuki Kawashima, Shoji Natsugoe, Tetsuro Setoyama, Shinkan Tokudome, Koshi Mimori, Naotsugu Haraguchi, Hideshi Ishii, Masaki Mori

Research output: Contribution to journalArticle

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Abstract

Background: Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective: To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods: A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results: Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10-40 and OR=4.13, p=8.4×10-76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions: Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.

Original languageEnglish
Pages (from-to)1457-1464
Number of pages8
JournalGut
Volume59
Issue number11
DOIs
Publication statusPublished - Nov 1 2010

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Alcohol Drinking
Smoking
Alleles
Odds Ratio
Single Nucleotide Polymorphism
Esophageal Squamous Cell Carcinoma
Genome-Wide Association Study
Secondary Prevention
Smoke
Alcohols

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles. / Tanaka, Fumiaki; Yamamoto, Ken; Suzuki, Sadao; Inoue, Hiroshi; Tsurumaru, Masahiko; Kajiyama, Yoshiaki; Kato, Hoichi; Igaki, Hiroyasu; Furuta, Koh; Fujita, Hiromasa; Tanaka, Toshiaki; Tanaka, Yoichi; Kawashima, Yoshiyuki; Natsugoe, Shoji; Setoyama, Tetsuro; Tokudome, Shinkan; Mimori, Koshi; Haraguchi, Naotsugu; Ishii, Hideshi; Mori, Masaki.

In: Gut, Vol. 59, No. 11, 01.11.2010, p. 1457-1464.

Research output: Contribution to journalArticle

Tanaka, F, Yamamoto, K, Suzuki, S, Inoue, H, Tsurumaru, M, Kajiyama, Y, Kato, H, Igaki, H, Furuta, K, Fujita, H, Tanaka, T, Tanaka, Y, Kawashima, Y, Natsugoe, S, Setoyama, T, Tokudome, S, Mimori, K, Haraguchi, N, Ishii, H & Mori, M 2010, 'Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles', Gut, vol. 59, no. 11, pp. 1457-1464. https://doi.org/10.1136/gut.2009.205724
Tanaka, Fumiaki ; Yamamoto, Ken ; Suzuki, Sadao ; Inoue, Hiroshi ; Tsurumaru, Masahiko ; Kajiyama, Yoshiaki ; Kato, Hoichi ; Igaki, Hiroyasu ; Furuta, Koh ; Fujita, Hiromasa ; Tanaka, Toshiaki ; Tanaka, Yoichi ; Kawashima, Yoshiyuki ; Natsugoe, Shoji ; Setoyama, Tetsuro ; Tokudome, Shinkan ; Mimori, Koshi ; Haraguchi, Naotsugu ; Ishii, Hideshi ; Mori, Masaki. / Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles. In: Gut. 2010 ; Vol. 59, No. 11. pp. 1457-1464.
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T1 - Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles

AU - Tanaka, Fumiaki

AU - Yamamoto, Ken

AU - Suzuki, Sadao

AU - Inoue, Hiroshi

AU - Tsurumaru, Masahiko

AU - Kajiyama, Yoshiaki

AU - Kato, Hoichi

AU - Igaki, Hiroyasu

AU - Furuta, Koh

AU - Fujita, Hiromasa

AU - Tanaka, Toshiaki

AU - Tanaka, Yoichi

AU - Kawashima, Yoshiyuki

AU - Natsugoe, Shoji

AU - Setoyama, Tetsuro

AU - Tokudome, Shinkan

AU - Mimori, Koshi

AU - Haraguchi, Naotsugu

AU - Ishii, Hideshi

AU - Mori, Masaki

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective: To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods: A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results: Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10-40 and OR=4.13, p=8.4×10-76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions: Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.

AB - Background: Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective: To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods: A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results: Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10-40 and OR=4.13, p=8.4×10-76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions: Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.

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