Gender Disparities in Metastatic Colorectal Cancer Survival

Abstract

Purpose: Previous studies have shown that estrogen prevents colon cancer in postmenopausal women, indicating a role in colorectal cancer carcinogenesis and tumor progression. We investigated the interactions between sex, age, ethnicity, and year of diagnosis on overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Experimental Design: We screened 52,882 patients with MCRC from 1988 to 2004, using the Surveillance Epidemiology and End Results registry. Age at diagnosis, sex, ethnicity, tumor location, year of diagnosis, OS, and cancer-specific survival were evaluated using Cox proportional hazards model. The models were adjusted for marital status, tumor site, tumor differentiation, and treatment with radiation and/or surgery. Results: We observed that younger women (18-44 years old) with MCRC lived longer than younger men (17 months versus 14; P < 0.0001, log-rank test). In contrast, older women (55 years and older) had significantly worse OS than older men (7 months versus 9; P < 0.0001, log-rank test). In multivariate analysis, we found that gender discrepancies have widened in recent years; young women diagnosed after 2000 have improved cancer-specific survival, compared to men (hazard ratio, 0.778; 95% confidence interval, 0.669-0.904), but those diagnosed before 2000 benefit less (hazard ratio, 0.931; 95% confidence interval, 0.821-1.056). Conclusion: As one of the largest data sets analyzed to establish that younger women with MCRC survive longer than younger men, hormonal status not only seems to play an important role in the development and pathogenesis of colorectal cancer but also may be of prognostic significance. These data warrant further studies to determine the role of estrogen in colorectal cancer. ( The effect of gender on colorectal cancer (CRC) incidence is well established. At all ages, women are less likely to develop CRC than men (1, 2). Indeed, their risk is comparable to men 4 to 8 years younger in age (3). Variable environmental exposures and comorbidities may contribute to these findings; however, an alternate explanation is emerging.In the Women's Health Initiative trial, postmenopausal hormone use was associated with a 40% decrease in colorectal cancer (4). This association between hormone replacement therapy and colon cancer prevention is consistent with previous reports (5, 6). Hormones also protect premenopausal women, as oral contraceptive use reduces the risk of developing CRC by ∼20% (7, 8). The mechanism by which this occurs is unclear, but these findings parallel reports that menopause increases a woman's risk of developing colon cancer over premenopausal women of the same age (9).Gender differences in CRC extend to environmental sequelae, tumor biology, and therapeutic response. For example, obesity (10) and a sedentary lifestyle (11) increase the risk of colon cancer mostly in men. There is also evidence that tumorigenesis may be gender specific as women are more likely to develop right-sided tumors with the microsatelllite instability phenotyp...

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