Abstract 4802: Gender disparity in esophageal cancer incidence.

Introduction: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen remains unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Materials/Methods: We evaluated the Surveillance Epidemiology and End Results (SEER) cancer incidence trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each five year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger population and those with EAC histology as previously demonstrated. EAC and ESCC incidence rates both increases with aging, consistent with cancer being an age-related disease, but the male: female incidence ratio of EAC significantly decreased with aging. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female cohort. Interestingly, the APC doubled in the last two age groupings of older females (age 65-74 = + 0.3 and age 75 and greater = + 0.7). APC rates for the males increased gradually in all their age groups (age 50-64 = +1.2, age 65-74 = +1.4, age 75+ = +1.9). Conclusions: The males’ incidence of EAC increases at a steep rate with aging and females’ incidence rates are not as steep except after age 60-64 where their incidence rate of change steeply increases. The steeper change in EAC incidence rates in the post menopausal female may explain why the male: female EAC incidence ratio decreases with age as seen nationally (SEER). The negative APC in the female 50-64 years age group may be explained by their peri-menopausal state and by the increased use of post-menopausal hormonal therapy since 1975 for this age group. Using age as a proxy for estrogen exposure, our findings suggest a hormonal component for the observed age-related, declining male to female EAC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that the pre-menopausal estrogen milieu in females may serve as a protective factor against EAC. Moreover, this protective state dissipates with time in the post menopausal females where the effect of estrogen exposure dissipates. Implications: Our initial epidemiological observation of gender-age differences warrants translation into a molecular epidemiology study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen exposure in esophageal adenocarcinoma. Citation Format: Luckson N. Mathieu, Norma Kanarek, Craig Hooker, Malcolm Brock. Gender disparity in esophageal cancer incidence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4802. doi:10.1158/1538-7445.AM2013-4802