Abstract B51: Effect modification of the relationship between cigarette smoking and endometrial carcinoma risk
Authors: Felix Ashley S. , Yang Hannah P. , Gierach Gretchen L. , Park Yikyung , Brinton Louise A. 
Published: May 2019

Introduction: Epidemiological studies have consistently observed inverse associations between cigarette smoking and endometrial carcinoma risk. However, effect modification of this relationship by other endometrial carcinoma risk factors and relationships with tumor characteristics are unclear.

Methods: We examined the association between cigarette smoking and endometrial carcinoma risk among 110,304 women enrolled in the National Institutes of Health-AARP Diet and Health Study. During 1,029,041 person years of follow-up, we identified 1,476 incident endometrial carcinoma cases. Multivariable Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association between smoking status, years since smoking cessation, and endometrial carcinoma risk. Potential effect modification by other endometrial carcinoma risk factors was assessed using likelihood ratio test statistics. Smoking associations by histologic subtype (Type I vs. Type II) and stage at diagnosis (in situ/localized vs. regional/distant) were also evaluated.

Results: Reduced endometrial carcinoma risk was evident among former (RR: 0.88, 95% CI 0.79, 0.98) and current (RR: 0.67, 95% CI 0.55, 0.81) smokers compared with never smokers. Number of years since smoking cessation was significantly related to endometrial carcinoma risk: smoking cessation 1-4 years prior to baseline was associated with reduced endometrial carcinoma risk (RR: 0.66, 95% CI 0.49, 0.89) whereas smoking cessation 10 or more years before baseline was not significantly associated with risk (RR: 0.94, 95% CI 0.84, 1.06). The association between smoking status and endometrial carcinoma risk was modified by body mass index (BMI, pinteraction=0.02) and menopausal status (pinteraction=0.08). Among obese women (BMI &gt; 30 kg/m2), former (RR: 0.78, 95% CI 0.68, 0.92) and current smoking (RR: 0.59, 95% CI 0.42, 0.82) were inversely related to endometrial carcinoma risk. Smoking status was not associated with risk among overweight women (BMI 25-30 kg/m2); however, among normal-weight women (BMI &lt;25 kg/m2), current (RR: 0.59, 95% CI 0.42, 0.85) but not former smoking (RR: 1.04, 95% CI 0.85, 1.27) was related to endometrial carcinoma risk. Opposite associations for pre- and postmenopausal women were observed, with current smoking being inversely related to endometrial carcinoma risk in postmenopausal women (RR: 0.61, 95% CI 0.50, 0.74) but positively associated with endometrial carcinoma risk in premenopausal women (RR: 1.47, 95% CI 0.75, 2.88). No other endometrial carcinoma risk factors, including menopausal hormone use, parity, oral contraceptive use, or diabetes significantly modified the smoking-endometrial carcinoma risk relationship. We did not observe major differences in associations between smoking status and endometrial carcinoma risk by tumor characteristics.

Conclusion: Our results demonstrate that endometrial carcinoma risk is influenced by current as well as recent smoking history; however, associations did not vary meaningfully by endometrial tumor characteristics. Effect modification by some hormone-associated risk factors (e.g. menopausal status and obesity) but not others (e.g. menopausal hormones and oral contraceptive use) might suggest that smoking reduces endometrial carcinoma risk through multiple biological mechanisms.

Citation Format: Ashley S. Felix, Hannah P. Yang, Gretchen L. Gierach, Yikyung Park, Louise A. Brinton. Effect modification of the relationship between cigarette smoking and endometrial carcinoma risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B51.