No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study

作者：Rebbeck Timothy R^*; Antoniou Antonis C; Caldes Llopis Trinidad; Nevanlinna Heli; Aittomaki Kristiina; Simard Jacques; Spurdle Amanda B; Couch Fergus J; Pereira Lutecia H Mateus; Greene Mark H; Andrulis Irene L; Pasche Boris; Kaklamani Virginia; Hamann Ute; Szabo Csilla; Peock Susan; Cook Margaret; Harrington Patricia A; Donaldson Alan; Male Allison M; Gardiner Carol Anne; Gregory Helen; Side Lucy E; Robinson Anne C; Emmerson Louise; Ellis Ian

来源：Breast Cancer Research and Treatment, 2009, 115(1): 185-192.

DOI：10.1007/s10549-008-0064-8

• BRCA1
• BRCA2
• Risk modifiers
• Hereditary cancer

Background The transforming growth factor beta-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-beta, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers.

• 出版日期2009-5
• 单位河北医科大学; 西北大学