Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women
Menée aux Etats-Unis, cette étude de cohorte prospective (491 cas) évalue l'association entre des expositions à divers facteurs tels que le tabagisme, l'utilisation d'un traitement hormonal substitutif de la ménopause, une consommation de folates, le niveau d'expression de la protéine ESR2 et le risque de cancer colorectal chez des femmes âgées
Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer (CRC) risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor beta (ESR2) has been associated with CRC stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate -associated CRC risks by ESR2protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded CRC tissue specimens were collected and evaluated for ESR2protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between smoking, MHT, or folate and ESR2-defined CRC subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident CRC 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 to non-smokers). 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 to never use). No associations were found for folate. Conclusions: In this study, smoking and MHT were associated with ESR2expression patterns. Impact: These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women.