A Prospective Study of Duration of Smoking Cessation and Colorectal Cancer Risk by Epigenetics-related Tumor Classification
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Author
Nishihara, Reiko
Morikawa, Teppei
Kuchiba, Aya
Lochhead, Paul
Yamauchi, Mai
Liao, Xiaoyun
Imamura, Yu
Nosho, Katsuhiko
Shima, Kaori
Kawachi, Ichiro
Qian, Zhi Rong
Fuchs, Charles S.
Chan, Andrew T.
Giovannucci, Edward
Ogino, Shuji
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https://doi.org/10.1093/aje/kws431Metadata
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Nishihara, Reiko, Teppei Morikawa, Aya Kuchiba, Paul Lochhead, Mai Yamauchi, Xiaoyun Liao, Yu Imamura, et al. 2013. “A Prospective Study of Duration of Smoking Cessation and Colorectal Cancer Risk by Epigenetics-Related Tumor Classification.” American Journal of Epidemiology 178 (1): 84–100. https://doi.org/10.1093/aje/kws431.Abstract
The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression. Follow-up of 134,204 individuals in 2 US nationwide prospective cohorts (Nurses' Health Study (1980-2008) and Health Professionals Follow-up Study (1986-2008)) resulted in 1,260 incident rectal and colon cancers with available molecular data. Compared with current smoking, 10-19, 20-39, and >= 40 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95% confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (P-trend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (P-trend = 0.25) (P-heterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (P-heterogeneity = 0.02), DNMT3B expression (P-heterogeneity = 0.03), and BRAF (P-heterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41275482
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