Genetic heterogeneity in colorectal cancer associations between African and European americans.
Genetic heterogeneity in colorectal cancer associations between African and European americans.
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DOI：
10.1053/j.gastro.2010.07.038
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发表时间：
2010-11
期刊：
影响因子：
29.4
通讯作者：
Ellis NA
中科院分区：
文献类型：
--
作者：
Kupfer SS;Anderson JR;Hooker S;Skol A;Kittles RA;Keku TO;Sandler RS;Ellis NA
全基因组结直肠癌相关性研究已经确定了10个基因组区域的风险变异。这些研究中没有一项包括非裔美国人，他们是美国结直肠癌发病率和死亡率最高的群体。对于这10个基因组区域，我们对非洲裔和欧洲裔美国人进行了关联研究。我们对1194例结直肠癌患者(795名非洲裔美国人和399名欧洲裔美国人)和1352名对照(985名非洲裔美国人和367名欧洲裔美国人)的DNA样本中的22个单核苷酸多态(SNPs)进行了基因分型。在染色体8q24.21第3区，我们分析了1000例非裔美国人病例和1393名对照的6个SNPs。关联性检验使用多因素Logistic回归控制血统、年龄和性别。在欧洲裔美国人中测试的所有SNP的大小和关联方向与之前发表的研究一致，但在非裔美国人中测试的22个SNP中，有9个的关联方向相反。在非裔美国人中，位于8q24.21的SNP rs6983267与结直肠癌无关(优势比[OR]=1.18；P=0.12)；相反，8q24.21 SNP rs7014346(OR=1.15；p=0.03)与结直肠癌相关。在15q13.3位点，rs10318与两个群体的结直肠癌相关。在10p14，rs10795668的等位基因与非裔美国人的结直肠癌相关(OR=1.35；P=0.04)。在11q23.1处，rs3802842仅在非裔美国人中与直肠癌风险显著相关(OR 1.34；P=0.01)；这一观察结果在以前的研究中得到了证实。在欧洲裔美国人中，位于8q24.21、11q23.1和16q22.1的SNP与结直肠癌相关，这与以前的报告一致。在非裔美国人和欧洲人后裔中，结直肠癌相关基因存在遗传异质性。
Genome-wide association studies of colorectal cancer (CRC) have identified risk variants in 10 genomic regions. None of these studies included African Americans, who have the highest incidence and mortality from CRC in the US. For the 10 genomic regions, we performed an association study of Americans of African and European descent. We genotyped 22 single nucleotide polymorphisms (SNPs) in DNA samples from 1194 patients with CRC (795 African Americans and 399 European Americans) and 1352 controls (985 African Americans and 367 European Americans). At chromosome 8q24.21 region 3, we analyzed 6 SNPs from 1000 African American cases and 1393 controls. Association testing was done using multivariate logistic regression controlling for ancestry, age, and sex. Sizes and directions of association for all SNPs tested in European Americans were consistent with previously published studies, but for 9 of 22 SNPs tested in African Americans, they were of an opposite direction. Among African Americans, the SNP rs6983267 at 8q24.21 was not associated with CRC (odds ratio [OR]=1.18; P=0.12); instead, the 8q24.21 SNP rs7014346 (OR=1.15; p=0.03) was associated with CRC in this population. At 15q13.3, rs10318 was associated with CRC in both populations. At 10p14, the opposite allele of rs10795668 was associated with CRC in African Americans (OR=1.35; P=0.04). At 11q23.1, rs3802842 was significantly associated with rectal cancer risk only among African Americans (OR 1.34; P=0.01); this observation was made in previous studies. Among European Americans, SNPs at 8q24.21, 11q23.1, and 16q22.1 were associated with CRC, in agreement with previous reports. There is genetic heterogeneity in CRC associations in Americans of African vs. European descent.
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DOI：
10.1038/nrg2760
发表时间：
2010-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
30.8
作者：
Tomlinson, Ian P. M.;Webb, Emily;Houlston, Richard S.
通讯作者：
Houlston, Richard S.
影响因子：
29.4
作者：
Tomlinson, I;Rahman, N;Stratton, MR
通讯作者：
Stratton, MR
影响因子：
30.8
作者：
Pomerantz, Mark M.;Ahmadiyeh, Nasim;Jia, Li;Herman, Paula;Verzi, Michael P.;Doddapaneni, Harshavardhan;Beckwith, Christine A.;Chan, Jennifer A.;Hills, Adam;Davis, Matt;Yao, Keluo;Kehoe, Sarah M.;Lenz, Heinz-Josef;Haiman, Christopher A.;Yan, Chunli;Henderson, Brian E.;Frenkel, Baruch;Barretina, Jordi;Bass, Adam;Tabernero, Josep;Baselga, Jose;Regan, Meredith M.;Manak, J. Robert;Shivdasani, Ramesh;Coetzee, Gerhard A.;Freedman, Matthew L.
通讯作者：
Freedman, Matthew L.