Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.
Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.
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DOI：
10.1038/ncomms6260
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发表时间：
2014-10-20
影响因子：
16.6
通讯作者：
Ziv, Elad
中科院分区：
文献类型：
--
作者：
Fejerman, Laura;Ahmadiyeh, Nasim;Hu, Donglei;Huntsman, Scott;Beckman, Kenneth B.;Caswell, Jennifer L.;Tsung, Karen;John, Esther M.;Torres-Mejia, Gabriela;Carvajal-Carmona, Luis;Echeverry, Maria Magdalena;Tuazon, Anna Marie D.;Ramirez, Carolina;Gignoux, Christopher R.;Eng, Celeste;Gonzalez-Burchard, Esteban;Henderson, Brian;Le Marchand, Loic;Kooperberg, Charles;Hou, Lifang;Agalliu, Ilir;Kraft, Peter;Lindstroem, Sara;Perez-Stable, Eliseo J.;Haiman, Christopher A.;Ziv, Elad
拉丁裔人中乳腺癌发生的遗传因素还不是很清楚。在这里，我们开展了一项拉丁美洲乳腺癌的全基因组关联研究，并确定了一个全基因组显著的风险变异，位于雌激素受体1基因(ESR1；6q25区域)的5‘端。该变异的次要等位基因具有很强的保护性(rs140068132：优势比(OR)0.60，95%可信区间(CI)0.53-0.67，P=9×10−18)，起源于美洲原住民，与先前报道的6q25风险变异无关。雌激素受体阴性疾病的关联(OR0.34，95%CI0.21~0.54)强于雌激素受体阳性疾病(OR0.63，95%CI0.49~0.80；P异质性=0.01)，并且与乳腺癌的一个重要危险因素--乳房X线片的密度有关(P=0.001)。Rs140068132位于几个转录因子结合位点，与MCF-7核蛋白的凝胶迁移率分析表明，该基因座上的G/A等位基因存在差异结合。这些结果突显了在不同人群中进行研究的重要性。全基因组关联研究已经发现了与乳腺癌相关的基因变异，但它们与拉丁美洲乳腺癌发展的关系尚不清楚。在这里，作者对拉丁裔人的乳腺癌进行了GWA，并在6q25区域发现了一个重要的美洲原住民起源的保护性变异。
The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5′ of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53–0.67, P=9 × 10−18), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21–0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49–0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations. Genome-wide association studies (GWAS) have revealed gene variants associated with breast cancer, but their association with breast cancer development in Latinas is not clear. Here, the authors carry out a GWAS of breast cancer in Latinas and identify a significant protective variant of Indigenous American origin in the 6q25 region.
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DOI：
10.1164/rccm.200309-1293oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Burchard, EG;Avila, PC;Silverman, EK
通讯作者：
Silverman, EK
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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乳腺癌协会联盟（BCAC）中亚洲和欧洲基因组广泛关联研究的6q25乳腺癌的比较。
影响因子：
3.7
作者：
Hein R;Maranian M;Hopper JL;Kapuscinski MK;Southey MC;Park DJ;Schmidt MK;Broeks A;Hogervorst FB;Bueno-de-Mesquita HB;Muir KR;Lophatananon A;Rattanamongkongul S;Puttawibul P;Fasching PA;Hein A;Ekici AB;Beckmann MW;Fletcher O;Johnson N;dos Santos Silva I;Peto J;Sawyer E;Tomlinson I;Kerin M;Miller N;Marmee F;Schneeweiss A;Sohn C;Burwinkel B;Guénel P;Cordina-Duverger E;Menegaux F;Truong T;Bojesen SE;Nordestgaard BG;Flyger H;Milne RL;Perez JI;Zamora MP;Benítez J;Anton-Culver H;Ziogas A;Bernstein L;Clarke CA;Brenner H;Müller H;Arndt V;Stegmaier C;Rahman N;Seal S;Turnbull C;Renwick A;Meindl A;Schott S;Bartram CR;Schmutzler RK;Brauch H;Hamann U;Ko YD;GENICA Network;Wang-Gohrke S;Dörk T;Schürmann P;Karstens JH;Hillemanns P;Nevanlinna H;Heikkinen T;Aittomäki K;Blomqvist C;Bogdanova NV;Zalutsky IV;Antonenkova NN;Bermisheva M;Prokovieva D;Farahtdinova A;Khusnutdinova E;Lindblom A;Margolin S;Mannermaa A;Kataja V;Kosma VM;Hartikainen J;Chen X;Beesley J;Kconfab Investigators;AOCS Group;Lambrechts D;Zhao H;Neven P;Wildiers H;Nickels S;Flesch-Janys D;Radice P;Peterlongo P;Manoukian S;Barile M;Couch FJ;Olson JE;Wang X;Fredericksen Z;Giles GG;Baglietto L;McLean CA;Severi G;Offit K;Robson M;Gaudet MM;Vijai J;Alnæs GG;Kristensen V;Børresen-Dale AL;John EM;Miron A;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Grip M;Andrulis IL;Knight JA;Glendon G;Mulligan AM;Figueroa JD;García-Closas M;Lissowska J;Sherman ME;Hooning M;Martens JW;Seynaeve C;Collée M;Hall P;Humpreys K;Czene K;Liu J;Cox A;Brock IW;Cross SS;Reed MW;Ahmed S;Ghoussaini M;Pharoah PD;Kang D;Yoo KY;Noh DY;Jakubowska A;Jaworska K;Durda K;Złowocka E;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Shen CY;Yu JC;Hsu HM;Hou MF;Orr N;Schoemaker M;Ashworth A;Swerdlow A;Trentham-Dietz A;Newcomb PA;Titus L;Egan KM;Chenevix-Trench G;Antoniou AC;Humphreys MK;Morrison J;Chang-Claude J;Easton DF;Dunning AM
通讯作者：
Dunning AM
影响因子：
120.7
作者：
Chlebowski, RT;Hendrix, SL;McTiernan, A
通讯作者：
McTiernan, A
DOI：
10.1158/1055-9965.epi-09-1193
发表时间：
2010-04
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：
Fejerman L;Romieu I;John EM;Lazcano-Ponce E;Huntsman S;Beckman KB;Pérez-Stable EJ;González Burchard E;Ziv E;Torres-Mejía G
通讯作者：
Torres-Mejía G