Abstract

Abstract Background. Smoking is an established risk factor for colorectal cancer (CRC). The purpose of this study was to examine if the increased risk of CRC due to cigarette smoking differ by sex and tumor subsite in the Multiethnic Cohort (MEC). Methods: We analyzed data from 188,052 participants (45% men) who were enrolled in the MEC at 45-75 years of age between 1993 and 1996. We identified CRC cases overall and by anatomic subsite (proximal, distal and rectal) via linkage to the Hawaii and California Surveillance, Epidemiology, and End Results Program cancer registries through December 2013. We used Cox proportional hazards regressions to estimate multivariable-adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: During a mean follow-up of 16.7 ± 5.2 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. For men and women, the annual age-adjusted incidence rate was 126.4 and 91.8 per 100,000 person-years (truncated to ages 45-85), respectively. Men had a higher incidence rate than women for all three subsites of CRC. Men had a larger proportion of rectal and a lower proportion of proximal colon cancer than women.Altogether, 70% of the men and 44% of women reported to be ever smokers. Men compared with women ever smokers, had smoked for more years, smoked more cigarettes per day and consequently had smoked more pack-years. . For both men and women, age at diagnosis was lower for ever compared with never smokers. Among men, compared with never smokers, ever smokers had a 38% (HR=1.38; 95% CI: 1.15-1.65) higher risk of distal, but not of proximal (HR=1.03; 95% CI: 0.90-1.18) colon cancer. The corresponding figures for women were a 21% (HR=1.21; 95% CI: 1.07-1.37) higher risk of proximal, but not of distal (HR= 0.97; 95% CI: 0.81-1.16) colon cancer. We observed a direct association for the three (duration, number of cigarettes per day and number of pack-years) measures of smoking exposure with proximal (all Ptrend < 0.001) colon cancer for women and with distal (all Ptrend < 0.001) colon cancer for men. Male ever smokers had a 40% (HR=1.40; 95% CI: 1.16-1.69) and female ever smokers a 58% (HR=1.58; 95% CI: 1.28-1.95) higher risk of rectal cancer compared with sex specific never smokers. Heavy smokers i.e. those who had smoked >20 pack-years had a 61% (HR =1.61; 95% CI: 1.29-2.00) higher risk of rectal cancer for men and a doubling in risk for women (HR= 2.09; 95% CI: 1.54-2.83) compared with sex specific never smokers (Pheterogeneity by sex = 0.03). Conclusions: Our main findings shows that the smoking related colorectal cancer risk varies by sex for the subsites of colon cancer, and possibly also for rectal cancer. Citation Format: Inger T. Gram, Song-Yi Park, Lynne R. Wilkens, Christopher A. Haiman, Loïc Le Marchand. Smoking and risk of colorectal cancer by sex and histological subsites: the Multiethnic Cohort (MEC) study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 628.

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