Evidence for a link between TNFRSF11A and risk of breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Nu´ ria Bonifaci Marta Palafox Pasquale Pellegrini Ana Osorio Javier Benı´tez Paolo Peterlongo Siranoush Manoukian Bernard Peissel Da
- چاپ و سال / کشور: 2011
Description
Intracellular signaling mediated by the receptor activator of nuclear factor-jB [Rank, encoded by the tumor necrosis factor receptor superfamily, member 11a (Tnfrsf11a) gene] is fundamental for mammary gland development in mice, regulating the expansion of stem and progenitor cell compartments. Conversely, Rank overexpression in mice promotes abnormal proliferation and impairs differentiation, leading to an increased incidence of tumorigenesis. Here, we show that a common genetic variant near the 50-end of TNFRSF11A, rs7226991, is associated with breast cancer risk in the general population and among carriers of mutations in the breast cancer 2, early onset (BRCA2) gene. Akin to the results of the Cancer and Genetics Markers of Susceptibility initiative, combined analysis of rs7226991 in two Spanish case– control studies (1,365 controls and 1,323 cases in total) revealed a significant association with risk: odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.78–0.98, Ptrend = 0.025. Subsequent examination of BRCA1 (n = 1,017) and BRCA2 (n = 885) mutation carriers revealed a consistent association in the latter group: weighted hazard ratio (wHR) = 0.70; 95% CI 0.55–0.88; and Ptrend = 0.003; compared to BRCA1 mutation carriers, wHR = 0.91; 95% CI 0.76–1.10; and Ptrend = 0.33. The results of this study need to be replicated in other populations and with larger numbers of BRCA1/2 mutation carriers.
DOI 10.1007/s10549-011-1546-7 Received: 12 January 2011 / Accepted: 20 April 2011
