Postmenopausal Hormone Therapy Is Associated with a Reduced Risk of Colorectal Cancer Lacking CDKN1A Expression
Year: 2012
Type: article
Abstract: Experimental studies have shown that estrogen- or progesterone-activated signaling leads to growth inhibition effects on colon cancer cells through the upregulation of several cell-cycle regulators. However, epidemiologic studies evaluating hormone therapy use and colorectal cancer risk by the status of cell-cycle regulators are lacking. In this study, we used data from the prospective Nurses' Health Study to evaluate whether the association between hormone therapy use and colorectal cancer risk differs by the molecular pathologic status of microsatellite instability (MSI) and expression of cell-cycle-related tumor biomarkers, including CDKN1A (p21, CIP1), CDKN1B (p27, KIP1), and TP53 (p53) by immunohistochemistry. Duplication Cox regression analysis was used to determine an association between hormone therapy use, cancer risk, and specific tumor biomarkers in 581 incident colon and rectal cancer cases that occurred during 26 years of follow-up among 105,520 postmenopausal women. We found a difference between hormone therapy use and colorectal cancer risk according to CDKN1A expression (P(heterogeneity) = 0.01). Current hormone therapy use was associated with a reduced risk for CDKN1A-nonexpressed [multivariate relative risk (RR), 0.61; 95% confidence interval (CI), 0.46-0.82] but not for CDKN1A-expressed (RR, 1.32; 95% CI, 0.76-2.31) tumors. The lower risk for CDKN1A-nonexpressed but not for CDKN1A-expressed cancers was also present among current users of estrogen-alone therapy. We found no significant difference in the relations between hormone therapy use and cancer risk according to MSI, CDKN1B, or TP53 status. Together, our molecular pathological epidemiology findings suggest a preventive effect of hormone therapy against colorectal carcinogenesis that depends, in part, on loss of cyclin-dependent kinase inhibitor CDKN1A.
Source: Cancer Research
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, Epigenetic Events and Colorectal Cancer Epidemiology, Estrogen and Progesterone-related Gene Variants and Colorectal Cancer Risk, Inflammation and Colorectal Neoplasia, Dietary and Hormonal Determinants of Cancer in Women, Sex steroid hormones, gene variants, and colorectal cancer, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital
OpenAlex ID: W2113417297