A genome-wide association study of prognosis in breast cancer.
A genome-wide association study of prognosis in breast cancer.
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DOI：
10.1158/1055-9965.epi-10-0085
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Kraft P
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文献类型：
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作者：
Azzato EM;Pharoah PD;Harrington P;Easton DF;Greenberg D;Caporaso NE;Chanock SJ;Hoover RN;Thomas G;Hunter DJ;Kraft P
乳腺癌的传统临床病理特征并不能解释生存率的所有差异。种系遗传变异可能提供额外的预后信息。我们对乳腺癌诊断后的生存进行了一项GWAS研究，通过从护士健康研究中扫描的1145名绝经后浸润性乳腺癌妇女（7711人年风险）获得528,252个snp的随访数据和基因分型信息。在SEARCH乳腺癌研究中，我们对4335名诊断为浸润性乳腺癌（38148年风险）的女性进行了10个最具统计学意义的基因座（最显著的SNP位于ARHGAP10， p = 2.28 × 10−7）的基因分型。在SEARCH研究中没有重复的基因座（均为p > 0.10）。假设至少有10个相关基因座，检测到至少一个次要等位基因频率为0.2的能力，在全基因组意义上赋予2.0的相对风险（5×10−8）是99%。我们没有发现任何与乳腺癌总体生存率相关的常见生殖系变异。我们的数据表明，不太可能存在对乳腺癌总体生存率有很大影响的常见种系变异（HR>2）。相反，与生存相关的常见变异可能对肿瘤亚型或治疗方法具有特异性，这似乎是合理的。需要有足够有力的新研究来发现与总体生存率或亚型或治疗亚组相关的新区域。
Traditional clinicopathological features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information. We conducted a GWAS study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 SNPs for 1,145 postmenopausal women with invasive breast cancer (7,711 person years at risk) from the Nurses’ Health Study scanned in the Cancer Genetic Markers of Susceptibility initiative. We genotyped the ten most statistically significant loci (most significant SNP located in ARHGAP10, p = 2.28 × 10−7) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH breast cancer study. None of the loci replicated in the SEARCH study (all p > 0.10). Assuming a minimum of ten associated loci, the power to detect at least one with a minor allele frequency of 0.2 conferring a relative hazard of 2.0 at genome-wide significance (5×10−8) was 99 percent. We did not identify any common germline variants associated with breast cancer survival overall. Our data suggest it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (HR>2). Instead, it is plausible that common variants associated with survival could be specific to tumor subtypes or treatment approaches. New studies, sufficiently powered, are needed to discover new regions associated with survival overall or by subtype or treatment subgroups.