Protein phosphatase 2A subunit gene haplotypes and proliferative breast disease modify breast cancer risk.
Protein phosphatase 2A subunit gene haplotypes and proliferative breast disease modify breast cancer risk.
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DOI：
10.1002/cncr.24702
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发表时间：
2010-01-01
期刊：
影响因子：
6.2
通讯作者：
Smith, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Dupont, William D.;Breyer, Joan P.;Bradley, Kevin M.;Schuyler, Peggy A.;Plummer, W. Dale;Sanders, Melinda E.;Page, David L.;Smith, Jeffrey R.
蛋白磷酸酶2A （Protein phosphatase 2A, PP2A）是一种重要的细胞磷酸酶，在细胞生长、分化和凋亡过程中起着重要的调控作用。被诊断为良性乳腺增生性疾病的妇女随后发展为乳腺癌的风险增加。我们评估了PP2A全酶亚基的遗传变异对乳腺癌风险的潜在贡献。我们对一组有良性乳腺疾病病史的妇女进行了巢式病例对照调查。研究对象的平均随访时间为18年；从原始档案良性乳腺活检（1954 - 1995）中提取的DNA可用于450名被诊断为乳腺癌的妇女的随访，以及900名在种族、年龄和进入活检年份上匹配的对照组中的890名。进行了基于单等位基因和单倍型的关联测试，并通过排列测试评估显著性。我们确定了PPP2R1A的显著风险和保护性单倍型，比值比分别为1.63 （95% CI 1.3 - 2.1）和0.55 （95% CI 0.41 - 0.76）。这些优势比在多重比较调整后仍然显著。具有PPP2R1A单倍型风险和增殖性乳腺疾病史的女性随后发展为乳腺癌的优势比为2.44 （95% CI 1.7 - 3.5）。两个调节亚基基因PPP2R2A和PPP2R5E的单倍型对乳腺癌风险的影响名义上是显著的，但经过多次比较调整后仍然不显著。这一证据支持了先前PP2A作为肿瘤抑制基因在乳腺癌中的作用的假设。
Protein phosphatase 2A (PP2A) is a major cellular phosphatase and plays key regulatory roles in growth, differentiation, and apoptosis. Women diagnosed with benign proliferative breast disease are at increased risk for the subsequent development of breast cancer. We evaluated genetic variation of PP2A holoenzyme subunits for potential contribution to breast cancer risk. We performed a nested case-control investigation of a cohort of women with a history of benign breast disease. Subjects were followed for an average of 18 years; DNA prepared from the original archival benign breast biopsy (1954 – 1995) was available for 450 women diagnosed with breast cancer on follow-up, and for 890 of their 900 controls who were matched on race, age, and year of entry biopsy. Single allele- and haplotype-based tests of association were conducted, with assessment of significance by permutation testing. We identified significant risk and protective haplotypes of PPP2R1A, giving odds ratios of 1.63 (95% CI 1.3 – 2.1) and 0.55 (95% CI 0.41 – 0.76), respectively. These odds ratios remained significant upon adjustment for multiple comparisons. Women with both the risk PPP2R1A haplotype and a history of proliferative breast disease had an odds ratio of 2.44 (95% CI 1.7 – 3.5) for the subsequent development of breast cancer. The effects of haplotypes for two regulatory subunit genes, PPP2R2A and PPP2R5E on breast cancer risk were nominally significant, but did not remain significant upon adjustment for multiple comparisons. This evidence supports the previously hypothesized role of PP2A as a tumor suppressor gene in breast cancer.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
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：
50.3
作者：
Neviani, P;Santhanam, R;Perrotti, D
通讯作者：
Perrotti, D
影响因子：
120.7
作者：
LONDON, SJ;CONNOLLY, JL;COLDITZ, GA
通讯作者：
COLDITZ, GA
影响因子：
4
作者：
Mumby, Marc
通讯作者：
Mumby, Marc