Confirmation of 5p12 as a susceptibility locus for progesterone-receptor-positive, lower grade breast cancer.
Confirmation of 5p12 as a susceptibility locus for progesterone-receptor-positive, lower grade breast cancer.
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DOI：
10.1158/1055-9965.epi-11-0569
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发表时间：
2011-10
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通讯作者：
Easton DF
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Milne RL;Goode EL;García-Closas M;Couch FJ;Severi G;Hein R;Fredericksen Z;Malats N;Zamora MP;Arias Pérez JI;Benítez J;Dörk T;Schürmann P;Karstens JH;Hillemanns P;Cox A;Brock IW;Elliot G;Cross SS;Seal S;Turnbull C;Renwick A;Rahman N;Shen CY;Yu JC;Huang CS;Hou MF;Nordestgaard BG;Bojesen SE;Lanng C;Grenaker Alnæs G;Kristensen V;Børrensen-Dale AL;Hopper JL;Dite GS;Apicella C;Southey MC;Lambrechts D;Yesilyurt BT;Floris G;Leunen K;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Chang-Claude J;Wang-Gohrke S;Radice P;Peterlongo P;Manoukian S;Barile M;Giles GG;Baglietto L;John EM;Miron A;Chanock SJ;Lissowska J;Sherman ME;Figueroa JD;Bogdanova NV;Antonenkova NN;Zalutsky IV;Rogov YI;Fasching PA;Bayer CM;Ekici AB;Beckmann MW;Brenner H;Müller H;Arndt V;Stegmaier C;Andrulis IL;Knight JA;Glendon G;Mulligan AM;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Meindl A;Heil J;Bartram CR;Schmutzler RK;Thomas GD;Hoover RN;Fletcher O;Gibson LJ;dos Santos Silva I;Peto J;Nickels S;Flesch-Janys D;Anton-Culver H;Ziogas A;Sawyer E;Tomlinson I;Kerin M;Miller N;Schmidt MK;Broeks A;Van 't Veer LJ;Tollenaar RA;Pharoah PD;Dunning AM;Pooley KA;Marme F;Schneeweiss A;Sohn C;Burwinkel B;Jakubowska A;Lubinski J;Jaworska K;Durda K;Kang D;Yoo KY;Noh DY;Ahn SH;Hunter DJ;Hankinson SE;Kraft P;Lindstrom S;Chen X;Beesley J;Hamann U;Harth V;Justenhoven C;GENICA Network;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Grip M;Hooning M;Hollestelle A;Oldenburg RA;Tilanus-Linthorst M;Khusnutdinova E;Bermisheva M;Prokofieva D;Farahtdinova A;Olson JE;Wang X;Humphreys MK;Wang Q;Chenevix-Trench G;kConFab Investigators;AOCS Group;Easton DF
研究发现5 p12-rs 10941679单核苷酸多态性与乳腺癌，特别是雌激素受体（ER）阳性疾病的风险相关。我们的目的是在乳腺癌协会联盟中进一步探讨这种整体相关性，并通过肿瘤组织病理学进行研究。数据来自37项研究，包括40，972例浸润性病例，1，398例导管原位癌（DCIS）和46，334例对照，所有白色欧洲血统，以及3，007例浸润性病例和2，337例亚洲血统对照。使用逻辑回归分析评估了总体相关性以及肿瘤侵袭性和组织病理学相关性。对于欧洲白色人，与5 p12-rs 10941679相关的每个等位基因比值比（OR）在浸润性乳腺癌中为1.11（95%置信区间[CI] =1.08-1.14，P=7×10−18），在DCIS中为1.10（95% CI =1.01-1.21，P=0.03）。对于亚洲女性，浸润性疾病的估计OR相似（OR=1.07，95%CI=0.99-1.15，P=0.09）。进一步的分析表明，在白色欧洲人中，这种关联主要限于孕激素受体（PR）阳性疾病（PR阴性疾病的每等位基因OR=1.16，95%CI=1.12-1.20，P=1×10−18 vs OR=1.03，95%CI=0.99-1.07，P=0.2; P异质性=2×10−7）;一旦考虑到PR状态，则未观察到雌激素受体状态的异质性（P=0.2）。低级别肿瘤的相关性也更强（1级、2级和3/4级的每等位基因OR [95%CI]分别为1.20 [1.14-1.25]、1.13 [1.09-1.16]和1.04 [0.99-1.08]; P趋势=5×10−7）。5 p12是PR阳性、低级别乳腺癌的易感基因。需要对该区域进行多中心精细定位研究，作为确定致病变异的第一步。
The single nucleotide polymorphism 5p12-rs10941679has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS) and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. For white Europeans, the per-allele odds ratio (OR) associated with 5p12-rs10941679 was 1.11 (95% confidence interval [CI] =1.08–1.14, P=7×10−18) for invasive breast cancer and 1.10 (95%CI=1.01–1.21, P=0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR=1.07, 95%CI=0.99–1.15, P=0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR=1.16, 95%CI=1.12–1.20, P=1×10−18 versus OR=1.03, 95%CI=0.99–1.07, P=0.2 for PR-negative disease; P-heterogeneity=2×10−7); heterogeneity by estrogen receptor status was not observed (P=0.2) once PR status was accounted for. The association was also stronger for lower-grade tumors (per-allele OR [95%CI]=1.20 [1.14–1.25], 1.13 [1.09–1.16] and 1.04 [0.99–1.08] for grade 1, 2 and 3/4, respectively; P–trend=5×10−7). 5p12 is a breast cancer susceptibility locus for PR-positive, lower gradebreast cancer. Multi-centre fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.