Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women

作者：Tillmans Lori S; Vierkant Robert A; Wang Alice H; Samadder Niloy Jewel; Lynch Charles F; Anderson Kristin E; French Amy J; Haile Robert W; Harnack Lisa J; Potter John D; Slager Susan L; Smyrk Thomas C; Thibodeau Stephen N; Cerhan James R; Limburg Paul J^*

来源：Cancer Epidemiology Biomarkers & Prevention, 2015, 24(4): 713-719.

DOI：10.1158/1055-9965.EPI-14-0756

Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor beta (ESR2) has been associated with colorectal cancer stage and survival.
Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes.
Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81-9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05-4.41 for ESR2-high for >= 40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26-1.13 for > 5 years compared with never use). No associations were found for folate.
Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns.
Impact: These data support possible heterogeneous effects from smoking and MHT on ER beta-related pathways of colorectal carcinogenesis in older women.

• 出版日期2015-4