Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women

被引：80

作者：

Rebbeck, Timothy R. ^{[1
,2
,3
]}

DeMichele, Angela ^{[1
,4
]}

Tran, Teo V. ^{[2
,3
]}

Panossian, Saarene ^{[2
,3
]}

Bunin, Greta R. ^{[5
,6
]}

Troxel, Andrea B. ^{[1
,2
,3
]}

Strom, Brian L. ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[5] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

来源：

CARCINOGENESIS | 2009年 / 30卷 / 02期

关键词：

ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR-ALPHA; GENOME-WIDE ASSOCIATION; REPLACEMENT THERAPY; ENDOMETRIAL CANCER; ESTROGEN/PROGESTIN REPLACEMENT; PLUS PROGESTIN; CELLS; RISK; DISEASE;

D O I：

10.1093/carcin/bgn247

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway and have been identified from genome-wide association studies to be breast cancer susceptibility genes. Potential interactions of these genes and their role with respect to tumor markers, hormonal factors and race on breast cancer risk have not been explored. We examined FGFR2 and MAP3K1 variants, breast tumor characteristics and hormone exposures in a population-based case-control sample of 1225 European-American (EA) and 584 African-American (AA) women. FGFR2 rs1219648 and rs2981582 genotypes were significantly associated with breast cancer in EA only in estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and HER2/Neu-negative (HER2-) tumors. MAP3K1 was not associated with breast cancer in EA women, but it was associated with breast cancer in AA women, again limited to ER+, PR+ and HER2- tumors. An interaction was observed between combined hormone replacement therapy use and FGFR2 rs1219648 genotypes on breast cancer risk in EA women (P = 0.010). Finally, we observed a significant interaction between MAP3K1 rs889312 and FGFR2 rs2981582 (P = 0.022) in AA but not EA women. These results confirm that FGFR2 and MAP3K1 are involved in breast cancer susceptibility and confer their effects primarily in ER+ and PR+ tumors. We further report that these genes confer their effects in HER2- tumors, interact with one another to confer breast cancer susceptibility in AA women and interact with hormone exposures in AA and EA women.

引用

页码：269 / 274

页数：6

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