Sex, Age, and Ethnicity are Associated with Survival in Metastatic Colorectal Cancer

1. Sex, Age, and Ethnicity are Associated with Survival in Metastatic Colorectal Cancer Andrew Hendifar, Georg Lurje, Felicitas Lenz, Alexandra Pohl, Phillip Manegold, Kayo Togawa, Heinz-Josef Lenz, Dongyun YangDivision of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA Introduction Methods Graphs and Figures At all ages, women are less likely to develop colorectal cancer (CRC) than men [1]. In fact their risk is comparable to men aged between 4-8 year younger [2]. Gender differences have also been associated with tumor biology, therapeutic response, and disease prognosis. Dietary and genetic differences may explain these inequalities, but evidence is accumulating for a hormonal etiology. The Women’s Health Initiative confirmed that post-menopausal hormone use is associated with a 40% decrease in colorectal cancer [3]. Although, the role of estrogen in CRC tumorigenesis is unclear, investigators have found that estrogen receptor β is selectively lost in malignant colonic tissue [4]. Age and ethnicity have been shown to impact the survival rates of men and women with metastatic colorectal cancer (MCRC). Yet gender is neither prognostic nor predictive for overall survival (OS). We investigated the interactions between sex, age, and ethnicity on overall survival in patients with MCRC. 1. Farquhar CM, Marjoribanks J, Lethaby A, Lamberts Q, Suckling JM, Cochrane Database Syst. Rev. CD004143 (2005) 2. Brenner, H., et al., Gender differences in colorectal cancer: implications for age at initiation of screening. Br J Cancer, 2007. 96(5): p. 828-31. 3. Chlebowski, R.T., et al., Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med, 2004. 350(10): p. 991-1004. 4. Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW. Selective loss of estrogen receptor beta in malignant human colon. Cancer Res 2000. We screened 56,598 patients with MCRC from 1988-2003, using the Surveillance, Epidemiology, and End Results (SEER) registry. Age at diagnosis, sex, ethnicity, and overall survival were evaluated using Cox proportional hazards model. The models were adjusted for marital status, tumor site, and treatment with radiation and/or surgery. Models were stratified by SEER registry site and year of diagnosis. Table 1. Overall survival of patients with MCRC by age and sex. Results We observed that younger women (18-44 years old) with MCRC lived longer than younger men (17 months vs. 14, p<0.0001). In contrast, older women (75 and older) had significantly worse overall survival than older men (p<0.0001, See Table 1). As women age their risk becomes equivalent to men (Figure 1). This association was independent of ethnicity (Figure 2). Women were more likely to have right sided colon lesions and men more likely to have left sided colon lesions (P<0.0001, Figure 3). Among ethnicities, Hispanics had the longest overall survival across all age groups followed by Asians, Whites, African Americans, and Naïve Americans, respectively (P<0.0001, Figure 4). Across all ethnicities younger patients had a better prognosis except for Native Americans; Patients from 18-44 years had the worst prognosis and an overall survival of 8 months. Months Hispanic African American Asian Native American White Hazard Ratio adjusted for marital status, tumor site, and treatment with radiation and/or surgery. Stratified by SEER registry site and year of diagnosis. Figure 3. Tumor Location and Gender Figure 4. Ethnicity and Overall Survival Conclusions Our data suggests that sex, age, and ethnicity have a significant impact on overall survival in MCRC patients. As one of the largest data sets analyzed to establish that younger women of all ethnicities survive longer than younger men, hormonal status appears to play an important role not only in the development and pathogenesis of colorectal cancer, but may be of prognostic significance. This also lends support to the importance of sex-specific differences in EGFR and MTHFR polymorphisms, as prognostic markers in CRC. These data warrant further studies to determine the role of estrogen in colorectal cancer development, growth, and progression.