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.
- Esophageal cancer
- cancer epidemiology, cancer prevention
- gene mutation
- oesophageal cancer
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Funding This work was supported in part by the following grants and foundations: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17109013, 21229015; CREST, Japan Science and Technology Agency (JST); NEDO (New Energy and Industrial Technology Development Organization) Technological Development for Chromosome Analysis; and The Ministry of Education, Culture, Sports, Science, and Technology of Japan for Scientific Research on Priority Areas, Cancer Translational Research Project, Japan. Other Funders: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, Japan Science and Technology Agency, New Energy and Industrial Technology Development Organization.
Competing interests None.
Ethics approval This study was conducted with the approval of the Kyusyu University, Juntendo University, National Cancer Institute, Saitama Cancer Center, Kurume University, and Kurume University, Japan.
Provenance and peer review Not commissioned; externally peer reviewed.
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