Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):1140-3. doi: 10.1158/1055-9965.EPI-10-0085. Epub 2010 Mar 23.
Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information.
We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms 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 10 most statistically significant loci (most significant single-nucleotide polymorphism located in ARHGAP10; P = 2.28 x 10(-7)) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study.
None of the loci replicated in the SEARCH study (all P > 0.10). Assuming a minimum of 10 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 (P = 5 x 10(-8)) was 99%.
We did not identify any common germline variants associated with breast cancer survival overall.
Our data suggest that it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (hazard ratio >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.
传统的乳腺癌临床病理特征不能解释所有的生存差异。种系遗传变异可能提供额外的预后信息。
我们对 528252 个单核苷酸多态性进行了全基因组关联研究，这些单核苷酸多态性来自参加护士健康研究的 1145 例绝经后浸润性乳腺癌女性（风险 7711 人年），并获得了随访数据和基因分型信息。我们对参加癌症遗传易感因素研究的 4335 例浸润性乳腺癌女性（风险 38148 人年）中的 10 个最显著的单核苷酸多态性（最显著的单核苷酸多态性位于 ARHGAP10 中；P=2.28×10(-7))进行了基因分型。在 SEARCH（癌症遗传因素研究中的流行病学和风险因素）乳腺癌研究中。
没有一个位点在 SEARCH 研究中得到复制（所有 P>0.10）。假设至少有 10 个相关位点，检测到至少一个次要等位基因频率为 0.2 的位点的概率为 99%，其相对危险度为 2.0，基因组显著性水平为 5×10(-8)。
我们没有发现任何与乳腺癌总体生存相关的常见种系变异。
我们的数据表明，不太可能存在与乳腺癌总体生存相关的常见种系变异，其效应大小较大（危险比>2）。相反，与生存相关的常见变异可能是特定于肿瘤亚型或治疗方法的。需要新的、有足够效力的研究来发现与总体生存或按肿瘤亚型或治疗亚组生存相关的新区域。
