Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).
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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。
DOI：
10.1371/journal.pone.0042380
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dunning AM
中科院分区：
文献类型：
--
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
6q25.1 位点首次通过中国女性的全基因组关联研究 (GWAS) 鉴定出来，并以单核苷酸多态性 (SNP) rs2046210 进行标记，位于 ESR1 上游约 180 Kb 处。关于该基因座与欧洲人乳腺癌的关联存在相互矛盾的报道，欧洲人的 GWAS 发现了一个不同的 SNP，此处标记为 rs12662670。我们在乳腺癌协会联盟合作的 44 项研究中检查了多达 61,689 例病例和 58,822 例对照中这两种 SNP 的关联，其中 4 项研究针对亚洲人，39 项研究针对欧洲血统。 Logistic 回归用于估计比值比 (OR) 和 95% 置信区间 (CI)。仅病例分析用于比较雌激素受体阳性 (ER+) 与阴性 (ER−) 肿瘤中 SNP 的影响。拟合包含两个 SNP 的模型来研究 SNP 效应是否独立。两个 SNP 均与两个种族群体的乳腺癌风险显着相关。亚洲人的每等位基因 OR 高于欧洲研究 [rs2046210：OR (A/G) = 1.36 (95% CI 1.26–1.48)，亚洲人的 p = 7.6×10−14 和 1.09 (95% CI 1.07–1.11)，在欧洲人中，p = 6.8×10−18。 rs12662670：OR (G/T) = 1.29 (95% CI 1.19–1.41)，亚洲人中 p = 1.2×10−9，欧洲人中 1.12 (95% CI 1.08–1.17)，p = 3.8×10−9]。在欧洲人中，SNP rs2046210 与 ER− 肿瘤风险显着高于 ER+ 肿瘤相关 [OR (ER−) = 1.20 (95% CI 1.15–1.25)，p = 1.8×10−17 与 OR (ER+) = 1.07 (95% CI 1.04–1.1)， p = 1.3×10−7，异质性 = 5.1×10−6]。相比之下，在这些亚洲研究中，没有明确的证据表明肿瘤受体状态存在差异关联。每个 SNP 与其他 SNP 调整后的风险相关。这些结果表明 6q25.1 存在两种变异，每种变异都与亚洲人和欧洲人的乳腺癌风险独立相关。在这两者中，被 rs2046210 标记的一个与 ER− 肿瘤的风险更大有关。
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER−) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26–1.48), p = 7.6×10−14 in Asians and 1.09 (95% CI 1.07–1.11), p = 6.8×10−18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19–1.41), p = 1.2×10−9 in Asians and 1.12 (95% CI 1.08–1.17), p = 3.8×10−9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER− than ER+ tumours in Europeans [OR (ER−) = 1.20 (95% CI 1.15–1.25), p = 1.8×10−17 versus OR (ER+) = 1.07 (95% CI 1.04–1.1), p = 1.3×10−7, pheterogeneity = 5.1×10−6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER− tumours.
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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：
通讯作者：
--
影响因子：
4.5
作者：
Stacey SN;Sulem P;Zanon C;Gudjonsson SA;Thorleifsson G;Helgason A;Jonasdottir A;Besenbacher S;Kostic JP;Fackenthal JD;Huo D;Adebamowo C;Ogundiran T;Olson JE;Fredericksen ZS;Wang X;Look MP;Sieuwerts AM;Martens JW;Pajares I;Garcia-Prats MD;Ramon-Cajal JM;de Juan A;Panadero A;Ortega E;Aben KK;Vermeulen SH;Asadzadeh F;van Engelenburg KC;Margolin S;Shen CY;Wu PE;Försti A;Lenner P;Henriksson R;Johansson R;Enquist K;Hallmans G;Jonsson T;Sigurdsson H;Alexiusdottir K;Gudmundsson J;Sigurdsson A;Frigge ML;Gudmundsson L;Kristjansson K;Halldorsson BV;Styrkarsdottir U;Gulcher JR;Hemminki K;Lindblom A;Kiemeney LA;Mayordomo JI;Foekens JA;Couch FJ;Olopade OI;Gudbjartsson DF;Thorsteinsdottir U;Rafnar T;Johannsson OT;Stefansson K
通讯作者：
Stefansson K
影响因子：
4.5
作者：
Dunbier AK;Anderson H;Ghazoui Z;Lopez-Knowles E;Pancholi S;Ribas R;Drury S;Sidhu K;Leary A;Martin LA;Dowsett M
通讯作者：
Dowsett M