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

研究成果: Contribution to journalArticle査読

98 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1457-1464
ページ数8
ジャーナルGut
59
11
DOI
出版ステータス出版済み - 11 2010

All Science Journal Classification (ASJC) codes

  • 消化器病学

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