A PROSPECTIVE-STUDY OF CIGARETTE-SMOKING AND RISK OF COLORECTAL ADENOMA AND COLORECTAL-CANCER IN UNITED-STATES WOMEN

Background: A positive correlation between smoking and colorectal cancer has been reported for men, but not for women, who began smoking in substantial numbers in the late 1940s and early 1950s. We hypothesized that smoking acts as an initiator of colorectal neoplasia and that an association with cancer in women has been missed because of the long period between initiation and diagnosis of cancer. Purpose: Our purpose was to assess the association between smoking and risk of colorectal adenoma and colorectal cancer in women and to estimate the minimum induction period between the onset of smoking and cancer diagnosis. Methods: Our data came from the ongoing Nurses' Health Study, in which current and lifetime smoking histories and other potential confounding factors were assessed by questionnaire at baseline and at 2-year intervals. We documented 586 new cases of colorectal cancer from 1976 to 1990 from a group of 118334 women and 564 new cases of adenoma among 12143 women who had a first colonoscopy or sigmoidoscopy between 1980 and 1990. We then assessed the relative risk (RR) of small adenoma, large adenoma (greater-than-or-equal-to 1 cm), and colorectal cancer in terms of pack-years of smoking. Results: The amount smoked in the prior 20 years was related to the prevalence of small adenomas (multivariate RR = 1.45; 95% confidence interval [CI] = 1.25-1.68; P<.0001) and less strongly with large adenomas (RR = 1.31; 95% CI = 1.17-1.47; P<.0001), adjusting for age, intake of saturated fat, dietary fiber, folate, and alcohol, body mass, family history of colorectal cancer, and pack-years of cigarettes smoked within the prior 20 years. Pack-years of cigarettes smoked more than 20 years in the past was associated with risk of large adenoma (multivariate RR for a 20 pack-year increment = 1.29; 95% CI = 1.01-1.64; P trend = .04), but not of small adenoma (RR = 1.11; 95% CI = 0.93-1.34). Cigarette smoking was unrelated to colorectal cancer until 35 years after smoking began, but then became progressively more strongly related with time. Among women who had started smoking more than 10 cigarettes per day 35-39 years in the past, the RR for cancer was 1.47 (95% CI = 1.07-2.01), progressing to 1.63 (95% CI = 1.14-2.33) after 40-44 years and 2.00 (95% CI = 1.14-3.49) after 45 years. Conclusions: Because the minimum induction period for colorectal cancer appears to be at least 35 years, an association between smoking and colorectal cancer in women may just now be showing up. Implications: Our findings suggest that cigarette smoking may be a previously unrecognized, preventable cause of colorectal cancer among women.