A family-based, genome-wide association study of young-onset breast cancer: inherited variants and maternally mediated effects.
A family-based, genome-wide association study of young-onset breast cancer: inherited variants and maternally mediated effects.
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一项针对年轻发病乳腺癌的基于家庭的全基因组关联研究：遗传变异和母体介导的影响。
DOI：
10.1038/ejhg.2016.11
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Weinberg,ClariceR
中科院分区：
文献类型：
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作者：
O'Brien,KatieM;Shi,Min;Sandler,DaleP;Taylor,JackA;Zaykin,DmitriV;Keller,Jean;Wise,AlisonS;Weinberg,ClariceR
年轻发病的乳腺癌与老年发病的乳腺癌在表型和病因学上存在一定差异，并可能受到一些不同的遗传变异的影响。很少有针对年轻女性的乳腺癌遗传研究，也没有研究检查母体变异是否通过产前效应影响成年女儿的疾病。我们进行了一项以家族为基础的、全基因组的非典型性乳腺癌关联研究（诊断时年龄< 50岁）。对1279例非西班牙裔白色病例及其父母或姐妹篇共602188个单核苷酸多态性（SNP）进行基因分型。我们使用基于似然的对数线性模型来检验家庭内的传播不对称性和母体介导的遗传效应。三个常染色体SNPs（rs 28373882，P= 2.8× 10− 7; rs 879162，P= 9.2× 10− 7; rs 12606061，P= 9.1× 10− 7）与乳腺癌的风险相关，错误发现率低于0.20。这些基因座以前都没有与乳腺癌发病或总体乳腺癌风险相关，它们的功能作用尚不清楚。没有证据表明母体介导的、X连锁的或线粒体遗传效应，并且在由绝经状态、雌激素受体状态或肿瘤侵袭性定义的癌症亚类中没有显著发现。需要进一步的研究来探索其他潜在的遗传、表观遗传或上位性机制，并确认这三个新基因座与乳腺癌之间的关联。
Young-onset breast cancer shows certain phenotypic and etiologic differences from older-onset breast cancer and may be influenced by some distinct genetic variants. Few genetic studies of breast cancer have targeted young women and no studies have examined whether maternal variants influence disease in their adult daughters through prenatal effects. We conducted a family-based, genome-wide association study of young-onset breast cancer (age at diagnosis< 50 years). A total of 602 188 single-nucleotide polymorphisms (SNPs) were genotyped for 1279 non-Hispanic white cases and their parents or sisters. We used likelihood-based log-linear models to test for transmission asymmetry within families and for maternally mediated genetic effects. Three autosomal SNPs (rs28373882, P= 2.8× 10− 7; rs879162, P= 9.2× 10− 7; rs12606061, P= 9.1× 10− 7) were associated with risk of young-onset breast cancer at a false-discovery rate below 0.20. None of these loci has been previously linked with young-onset or overall breast cancer risk, and their functional roles are unknown. There was no evidence of maternally mediated, X-linked, or mitochondrial genetic effects, and no notable findings within cancer subcategories defined by menopausal status, estrogen receptor status, or by tumor invasiveness. Further investigations are needed to explore other potential genetic, epigenetic, or epistatic mechanisms and to confirm the association between these three novel loci and young-onset breast cancer.