Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women's Health Study.
Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women's Health Study.
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DOI：
10.1007/s10549-010-0775-5
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发表时间：
2010-09
影响因子：
3.8
通讯作者：
Palmer, Julie R.
中科院分区：
文献类型：
--
作者：
Ruiz-Narvaez, Edward A.;Rosenberg, Lynn;Rotimi, Charles N.;Cupples, L. Adrienne;Boggs, Deborah A.;Adeyemo, Adebowale;Cozier, Yvette C.;Adams-Campbell, Lucile L.;Palmer, Julie R.
在最近的一项欧洲血统女性全基因组关联研究（GWAS）中，染色体5 p12上的两个单核苷酸多态性（SNP）rs 4415084和rs 10941679与乳腺癌风险相关。这两个SNP都位于一个大的高LD区域，并且因果变异仍未知。我们在一组非裔美国妇女中进行了巢式病例对照研究，以复制和缩小携带因果变异的区域。我们评估了来自黑人妇女健康研究的886例乳腺癌病例和1，089例对照中索引SNP周围98 kb LD块中的14个标记SNP。我们使用Cochran-Armitage趋势检验来评估与乳腺癌风险的相关性。比值比来自logistic回归分析，调整了潜在的混杂因素，包括欧洲混合物的百分比。我们证实了报告的rs 4415084 SNP与乳腺癌总体风险的相关性（P = 0.06），并且与原始研究一样，观察到与雌激素受体阳性肿瘤的更强相关性（P = 0.03）。我们在标称α值为0.05的条件下，确定了与乳腺癌风险相关的另外4个SNP（rs6451770、rs 12515012、rs 13156930和rs 16901937）;所有这些SNP均位于59 kb HapMap YRI LD区块中。在多重检验校正后，与SNP rs 16901937的关联仍然显著（P排列= 0.038）。G等位基因与总体乳腺癌风险增加21%相关，与雌激素和孕激素受体阳性肿瘤增加32%相关。目前来自非洲血统（AA）人群的结果证实了染色体5 p12区域存在乳腺癌易感性遗传变异。我们成功地使用我们的AA样本中LD的较短范围来完善推定的因果变异的定位。
Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case–control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women's Health Study. We used the Cochran–Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant.
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影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
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：
3.5
作者：
Koc, EC;Ranasinghe, A;Spremulli, LL
通讯作者：
Spremulli, LL
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
30.8
作者：
Thomas, Gilles;Jacobs, Kevin B.;Kraft, Peter;Yeager, Meredith;Wacholder, Sholom;Cox, David G.;Hankinson, Susan E.;Hutchinson, Amy;Wang, Zhaoming;Yu, Kai;Chatterjee, Nilanjan;Garcia-Closas, Montserrat;Gonzalez-Bosquet, Jesus;Prokunina-Olsson, Ludmila;Orr, Nick;Willett, Walter C.;Colditz, Graham A.;Ziegler, Regina G.;Berg, Christine D.;Buys, Saundra S.;McCarty, Catherine A.;Feigelson, Heather Spencer;Calle, Eugenia E.;Thun, Michael J.;Diver, Ryan;Prentice, Ross;Jackson, Rebecca;Kooperberg, Charles;Chlebowski, Rowan;Lissowska, Jolanta;Peplonska, Beata;Brinton, Louise A.;Sigurdson, Alice;Doody, Michele;Bhatti, Parveen;Alexander, Bruce H.;Buring, Julie;Lee, I-Min;Vatten, Lars J.;Hveem, Kristian;Kumle, Merethe;Hayes, Richard B.;Tucker, Margaret;Gerhard, Daniela S.;Fraumeni, Joseph F., Jr.;Hoover, Robert N.;Chanock, Stephen J.;Hunter, David J.
通讯作者：
Hunter, David J.