Associations between Cigarette Smoking, Hormone Therapy and Folate Intake with Incident CRC by TP53 Expression Level in a Population-Based Cohort of Older Women
A partir des données de la cohorte "Women's Health Study" incluant 41 836 femmes âgées de 55 à 69 ans, cette étude prospective américaine évalue l'association entre le tabagisme, l'utilisation d'un traitement hormonal substitutif de la ménopause, une consommation de folates et le risque de cancer colorectal en fonction du niveau d'expression du gène p53
Cigarette smoking (CS), hormone therapy (HT) and folate intake (FI) are each thought to influence colorectal cancer (CRC) risk, but the underlying molecular mechanisms remain incompletely defined. The TP53 (p53) protein, encoded by the TP53 tumor suppressor gene that is commonly mutated in CRC, can be readily assessed to differentiate biologically distinct CRC subtypes. In this prospective cohort study, we examined CS, HT, and FI -associated CRC risks by TP53 protein expression level among Iowa Women's Health Study (IWHS) participants. The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry in 1986. Self-reported exposure variables were assessed at baseline. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected and evaluated for TP53 protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between CS, HT, or FI and TP53-defined CRC subtypes. Informative environmental exposure and protein expression data were available for 492 incident CRC cases: 222 (45.1%) TP53 negative, 72 (14.6%) TP53 low, and 198 (40.2%) TP53 high. Longer duration (> 5 years) of HT was inversely associated with TP53 high CRCs (RR = 0.50; 95% CI = 0.27-0.94). No other statistically significant associations were observed. These data support possible heterogeneous effects from HT on TP53-related pathways of colorectal carcinogenesis in older women.