A genome-wide association scan on estrogen receptor-negative breast cancer.
A genome-wide association scan on estrogen receptor-negative breast cancer.
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DOI：
10.1186/bcr2772
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Hall P
中科院分区：
文献类型：
--
作者：
Li J;Humphreys K;Darabi H;Rosin G;Hannelius U;Heikkinen T;Aittomäki K;Blomqvist C;Pharoah PD;Dunning AM;Ahmed S;Hooning MJ;Hollestelle A;Oldenburg RA;Alfredsson L;Palotie A;Peltonen-Palotie L;Irwanto A;Low HQ;Teoh GH;Thalamuthu A;Kere J;D'Amato M;Easton DF;Nevanlinna H;Liu J;Czene K;Hall P
乳腺癌是一种异质性疾病，可以根据肿瘤细胞中雌激素受体（ER）是否表达来确定其特征。乳腺癌的ER状态在临床上很重要，既可作为预后指标，也可作为治疗预测指标。在这项研究中，我们专注于识别与er阴性乳腺癌风险相关的遗传标记。我们对617例er阴性乳腺癌病例和4583例对照进行了285984个单核苷酸多态性（snp）基因分型的全基因组关联分析。我们还对发现数据集进行了全基因组通路分析，使用基于排列的预先定义通路测试。雌激素受体阴性乳腺癌和雌激素受体阳性乳腺癌之间共有的多基因变异程度是通过使用雌激素受体阳性乳腺癌样本得出的相关风险评分与独立的雌激素受体阴性乳腺癌病例的疾病状态进行评估的。在独立研究（1,011例er阴性乳腺癌病例，7,604例对照）中，没有证实与er阴性乳腺癌的关联。然而，发现在癌症相关途径中具有已知调节功能的snp的小P值过量（全局P = 0.052）。我们没有发现证据表明雌激素受体阴性乳腺癌与雌激素受体阳性乳腺癌具有多基因基础。er阴性乳腺癌是一种独特的乳腺癌亚型，值得独立分析。鉴于这种表型的临床重要性以及遗传效应较小的可能性，需要更大的样本量和进一步的研究来了解er阴性乳腺癌的病因。
Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk. We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases. Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer. ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.
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DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
3
作者：
Guo YF;Li J;Chen Y;Zhang LS;Deng HW
通讯作者：
Deng HW
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
影响因子：
30.8
作者：
Fagerholm, Rainer;Hofstetter, Barbara;Nevanlinna, Heli
通讯作者：
Nevanlinna, Heli
影响因子：
30.8
作者：
Bilguvar, Kaya;Yasuno, Katsuhito;Niemela, Mika;Ruigrok, Ynte M.;Fraunberg, Mikael von und zu;van Duijn, Cornelia M.;van den Berg, Leonard H.;Mane, Shrikant;Mason, Christopher E.;Choi, Murim;Gaal, Emilia;Bayri, Yasar;Kolb, Luis;Arlier, Zulfikar;Ravuri, Sudhakar;Ronkainen, Antti;Tajima, Atsushi;Laakso, Aki;Hata, Akira;Kasuya, Hidetoshi;Koivisto, Timo;Rinne, Jaakko;Ohman, Juha;Breteler, Monique M. B.;Wijmenga, Cisca;State, Matthew W.;Rinkel, Gabriel J. E.;Hernesniemi, Juha;Jaaskelainen, Juha E.;Palotie, Aarno;Inoue, Ituro;Lifton, Richard P.;Guenel, Murat
通讯作者：
Guenel, Murat