Evaluating 17 breast cancer susceptibility loci in the Nashville breast health study.
Evaluating 17 breast cancer susceptibility loci in the Nashville breast health study.
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DOI：
10.1007/s12282-014-0518-2
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发表时间：
2015-09
期刊：
影响因子：
4
通讯作者：
Long, Jirong
中科院分区：
文献类型：
--
作者：
Han, Mi-Ryung;Deming-Halverson, Sandra;Cai, Qiuyin;Wen, Wanqing;Shrubsole, Martha J.;Shu, Xiao-Ou;Zheng, Wei;Long, Jirong
Genome-wide association studies (GWAS) have discovered multiple genetic loci associated with breast cancer risk. Investigating these loci would be helpful to evaluate previous findings and identify causal variants for breast cancer. We evaluated index SNPs in17 of these loci in a study of 1,511 cases and 1,454 controls of European descent. We investigated the overall association with breast cancer and among subtypes defined as ER+ (estrogen receptor positive), ER− (estrogen receptor negative) and TNBC (triple-negative breast cancer). Combined effects of SNPs on breast cancer risk were assessed via a genetic risk score (GRS). We evaluated the contribution of both genetic variants and traditional risk factors to a breast cancer risk assessment model. Five of the 17 SNPs were significantly associated (P ≤ 0.05) with overall breast cancer in the same direction as previously reported: rs13387042 (2q35/TNP1), rs4973768 (3p24/SLC4A7), rs2046210 (6q25/ESR1), rs1219648 (10q26/FGFR2), and rs4784227 (16q12/TOX3). When stratified by breast cancer subtype, all five SNPs were associated (P<0.05) with ER+ cancer, three with ER− cancer (rs13387042, rs1219648, and rs4784227), and one with TNBC (rs1219648). A GRS, based on those five significant SNPs, showed strong association with overall breast cancer with ORs (95% CI) of 1.48 (1.22–1.79), 1.85 (1.52–2.25) and 2.26 (1.82–2.80), respectively, for each quartile, (P = 2.0×10−15). Traditional risk factors, including previous benign breast disease, breast cancer family history and parity, were significantly associated with breast cancer risk in the present study. These factors, together with the GRS, were used to build a breast cancer risk assessment model with a c statistic of 0.6321 from receiver operating characteristic (ROC) analysis. The contribution of the GRS to the model was greater than prior benign breast disease, family history and parity with the c statistic change of 0.0374, 0.0324, 0.0103, 0.0012, respectively. Our study demonstrates that five SNPs were associated with overall breast cancer, with stronger association for ER+ than ER− cancer as previously reported, and suggests that a risk assessment model incorporating the GRS from five loci is useful in identifying women at high risk of breast cancer.
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DOI：
10.1158/1055-9965.epi-10-0054
发表时间：
2010-09
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Long J;Shu XO;Cai Q;Gao YT;Zheng Y;Li G;Li C;Gu K;Wen W;Xiang YB;Lu W;Zheng W
通讯作者：
Zheng W
影响因子：
30.8
作者：
Zheng, Wei;Long, Jirong;Gao, Yu-Tang;Li, Chun;Zheng, Ying;Xiang, Yong-Bin;Wen, Wanqing;Levy, Shawn;Deming, Sandra L.;Haines, Jonathan L.;Gu, Kai;Fair, Alecia Malin;Cai, Qiuyin;Lu, Wei;Shu, Xiao-Ou
通讯作者：
Shu, Xiao-Ou
影响因子：
30.8
作者：
Stacey, Simon N.;Manolescu, Andrei;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
51.1
作者：
Zhang, Ben;Beeghly-Fadiel, Alicia;Long, Jirong;Zheng, Wei
通讯作者：
Zheng, Wei
影响因子：
1.9
作者：
DELONG, ER;DELONG, DM;CLARKEPEARSON, DI
通讯作者：
CLARKEPEARSON, DI