Differences in Colon Adenomas and Carcinomas Among Women and Men

Abstract

COLORECTAL CANCER REMAINS THE THIRD LEADING cause of cancer deaths among women and men in the United States, underscoring the need for more effective preventive strategies for both sexes. Many promising approaches are based on the adenoma-carcinoma paradigm of colon carcinogenesis. The clinical corollary to this model is that the presence of adenomas represents a robust marker of colon carcinogenesis. This leads to 2 distinct applications for colorectal cancer prevention: target for intervention and risk marker. Indeed, removing adenomas through colonoscopy has been shown to decrease future colorectal cancer occurrence by 75% to 90%. From a screening perspective, the colonoscopic adenoma identification is used clinically to gauge long-term risk and dictate the frequency of future colorectal cancer screening. Most data suggest that the effect of colorectal cancer is approximately equivalent in both sexes. In 2009, an estimated 71 380 women and 75 590 men will develop colorectal cancer. This is consistent with data from 1993-2003 in which women composed 50% of patients in an unselected cohort of 161 172 patients with colorectal cancer from US community cancer centers. Moreover, while estimates of incidence of colorectal cancer has suggested up to a 2-fold male predominance, the more robust lifetime risk estimates for US women and men are comparable (5.1% vs 5.5%, respectively). Taken together, this and other evidence would suggest that colorectal cancer is, by and large, a sex-neutral malignancy. Therefore, it would logically follow that colonic adenomas should also be equivalent in women and men. However, several large-scale studies have indicated that women have a substantially lower adenoma detection rate than men. For instance, in a cross-sectional analysis of 50 148 patients undergoing colonoscopybased screening program, Regula et al demonstrated that, compared with women, men had an adjusted odds ratio for advanced adenomas of 1.73 (95% confidence interval [CI], 1.52-1.98). Additionally, Schoenfeld et al noted that the relative risk (RR) of clinically significant neoplasia (advanced adenomas) in men was 1.91 (95% CI, 1.42-2.56) compared with women. In a recent metaanalysis including 924 932 adults, Nguyen et al reported that the RR of advanced neoplasia in men vs women was 1.83 (95% CI, 1.69-1.97). These findings would imply that adenomas (even those designated as advanced, ie, size 1 cm or high-grade dysplasia or 25% villous features) represent a less reliable marker of colorectal cancer risk in women than in men, and would lead to speculation that colonoscopic identification of adenomas may be less protective of colorectal cancer in women than in men. Although rigorous evidence for this hypothesis is lacking, an administrative database review by Bressler et al noted that women were 41% more likely than men to develop colorectal cancer despite undergoing colonoscopy (4.1% vs 2.9%, P .001). Other supportive evidence centers on the predilection for proximal lesions among women. Baxter et al demonstrated that even though having a colonoscopy was associated with decreased risk of subsequent colorectal cancer by two-thirds in the distal colon, no protective effect was found for lesions in the proximal colon. These studies suggest that the lower prevalence of adenomas in women may translate into possibly less efficacy of colonoscopy. There is biological precedence for the sex-related differential clinical behavior of colonic neoplasia. Randomized controlled studies have demonstrated the chemopreventive abilities of estrogens/progesterones, potentially mediated by the tumor suppressor role of estrogen receptor . Moreover, numerous studies have documented the higher proportion of microsatellite-unstable (MSI-high) lesion in women consonant with their slightly better prognosis. From a risk factor perspective, women appear to have differential sensitivity to the carcinogenic effect of cigarette smoking. From an epidemiological perspective, women develop more proximal colorectal cancer, but lesions generally occur somewhat later in life com-