Abstract
Background
Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated.
Methods
A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures.
Results
Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06–1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM.
Conclusions
We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.
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Acknowledgment
This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 20390360, 20591547, 20790960, 21591644, 21791295, 21791297, 215921014 and 21679006; and the Funding Program for Next Generation World-Leading Researchers (LS094); and NEDO (New Energy and Industrial Technology Development Organization) Technological Development for Chromosome Analysis.
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Shinya Ishimaru, Koshi Mimori and Ken Yamamoto contributed equally to this work.
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Ishimaru, S., Mimori, K., Yamamoto, K. et al. Increased Risk for CRC in Diabetic Patients with the Nonrisk Allele of SNPs at 8q24. Ann Surg Oncol 19, 2853–2858 (2012). https://doi.org/10.1245/s10434-012-2278-6
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DOI: https://doi.org/10.1245/s10434-012-2278-6