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Evaluation of gene-environment interactions for colorectal cancer susceptibility loci using case-only and case-control designs

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Authors
Song, Nan; Lee, Jeeyoo; Cho, Sooyoung; Kim, Jeongseon; Oh, Jae Hwan; Shin, Aesun
Issue Date
2019-12-18
Publisher
BMC
Citation
BMC Cancer, 19(1):1231
Keywords
Colorectal cancerGene-environment interactionSingle-nucleotide polymorphismCase-only designCase-control design
Abstract
Background
Genome-wide association studies (GWAS) have identified more than 40 colorectal cancer susceptibility loci, but only a small fraction of heritability was explained. To account for missing heritability, we investigated gene-environment interactions (G × Es) between GWAS-identified single-nucleotide polymorphisms (SNPs) and established risk or protective factors for colorectal cancer using both case-only and case-control study designs.

Methods
Data on 703 colorectal cancer cases and 1406 healthy controls from the National Cancer Center in Korea were used. We tested interactions between 31 GWAS-identified SNPs and 13 established risk or protective factors for colorectal cancer (family history, body mass index, history of colorectal polyps, inflammatory bowel disease, and diabetes mellitus, alcohol drinking, smoking, regular exercise, regular aspirin use, postmenopausal hormone replace therapy, red meat and processed meat intake, and dairy consumption). Logistic regression models were used to assess G × Es for colorectal cancer risk.

Results
The SNP rs4444235 at 14q22.2 interacted with regular exercise in colorectal cancer (pcase-only = 2.4 × 10− 3, pcase-control = 1.5 × 10− 3). The risk allele (C) of rs4444235 increased the risk of colorectal cancer in regularly exercising individuals (OR = 1.47, 95% CI = 1.02–2.10) but decreased the risk in non-exercising individuals (OR = 0.76, 95% CI = 0.62–0.94). Furthermore, the G × E between the SNP rs2423279 at 20p12.3 and regular aspirin use was statistically significant (pcase-only = 7.7 × 10− 3, pcase-control = 1.6 × 10− 3). The additive effect of the risk allele (T) of rs2423279 on colorectal cancer risk was increased among regular aspirin users (OR = 4.62, 95% CI = 1.97–10.80).

Conclusion
Our results suggest that SNP rs4444235 at 14q22.2 and SNP rs2423279 at 20p12.3 may interact with regular exercise and aspirin use in colorectal carcinogenesis.
ISSN
1471-2407
Language
English
URI
https://doi.org/10.1186/s12885-019-6456-9

http://hdl.handle.net/10371/164797
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College of Medicine/School of Medicine (의과대학/대학원)Preventive Medicine (예방의학전공)Journal Papers (저널논문_예방의학전공)
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