Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.
Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.
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DOI：
10.1186/s12885-015-1392-9
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发表时间：
2015-05-10
期刊：
影响因子：
3.8
通讯作者：
Palmieri G
中科院分区：
文献类型：
--
作者：
Palomba G;Loi A;Porcu E;Cossu A;Zara I;Budroni M;Dei M;Lai S;Mulas A;Olmeo N;Ionta MT;Atzori F;Cuccuru G;Pitzalis M;Zoledziewska M;Olla N;Lovicu M;Pisano M;Abecasis GR;Uda M;Tanda F;Michailidou K;Easton DF;Chanock SJ;Hoover RN;Hunter DJ;Schlessinger D;Sanna S;Crisponi L;Palmieri G
尽管在识别与乳腺癌相关的基因方面取得了进展，但仍存在更多的风险基因。在遗传同质的群体中进行全基因组关联分析，例如意大利撒丁岛的群体，可能是检测低外显性等位基因的另一种方法。我们进行了一项全基因组关联研究，比较了1431名患有非家族性BRCA1/2突变阴性乳腺癌的撒丁岛患者和2171名健康的撒丁岛献血者。使用基因芯片人类定位500 K阵列或全基因组人类SNP阵列6.0对DNA进行基因分型。为了增加基因组覆盖率，使用HapMap第二阶段的数据推算额外的SNPs的基因类型。在对基因数据进行质量控制筛选后，对总共2,067,645个SNPs进行了1367例(9名男性)和1658名对照(1156名男性)的分析。总体而言，33个基因组区域(67个候选SNP)在p <； 10−6水平上与乳腺癌风险相关。这些区域中有20个包含已定义的基因，包括一个已经与乳腺癌风险相关的基因：TOX3。在对p <； 10−5有初步意义的较低阈值下，我们在FGFR2中另外发现了11个SNP，FGFR2是一个公认的乳腺癌相关基因。选择了10个候选SNP，排除了那些已经与乳腺癌相关的SNP，用于技术验证和在同一人群的1668个样本中复制。只有位于VAV3内含子1的SNP rs345299仍然与乳腺癌相关(p值为1.16x10−5)，但在两个大型混合人群队列的汇集数据中，它与乳腺癌风险无关。本研究表明TOX3和FGFR2作为乳腺癌易感基因在撒丁岛人群BRCA1/2野生型乳腺癌患者中的作用。本文的在线版本(doi：10.1186/s12885-0151392-9)包含补充材料，授权用户可以使用。
Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10−6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10−5, we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10−5), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Palomba G;Loi A;Uras A;Fancello P;Piras G;Gabbas A;Cossu A;Budroni M;Contu A;Tanda F;Farris A;Orrù S;Floris C;Pisano M;Lovicu M;Santona MC;Landriscina G;Crisponi L;Palmieri G;Monne M
通讯作者：
Monne M
DOI：
10.1186/bcr3352
发表时间：
2012-11-05
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Quante AS;Whittemore AS;Shriver T;Strauch K;Terry MB
通讯作者：
Terry MB
影响因子：
7.3
作者：
Citterio, Carmen;Menacho-Marquez, Mauricio;Bustelo, Xose R.
通讯作者：
Bustelo, Xose R.