Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hum Genet. 2012 Jul;131(7):1173-85. doi: 10.1007/s00439-012-1139-5. Epub 2012 Jan 24.
Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.
Y 染色体上的遗传变异并未被令人信服地牵连到前列腺癌的风险中。为了全面分析欧洲血统个体中遗传 Y 染色体变异在前列腺癌风险中的作用，我们在来自四项研究的 3995 例前列腺癌病例和 3815 例对照中，对 34 个二进制 Y 染色体标记进行了基因分型。在这一组中，我们发现罕见的单倍群 E1b1b1c 与 I 期前列腺癌之间存在名义上的显著关联（P=0.012，OR=0.51；95%置信区间 0.30-0.87）。E1b1b1c 携带者的群体结构提示其与阿什肯纳兹犹太人的祖先有关，这促使我们在欧洲人和阿什肯纳兹犹太人后裔中进行了复制阶段的研究。对于阿什肯纳兹犹太人（1686 例病例和 1597 例对照）或欧洲人（686 例病例和 734 例对照）的研究，总体上前列腺癌的相关性并不显著（P(meta)=0.078），但对 I 期和 II 期研究的荟萃分析显示，与前列腺癌风险存在名义上的显著相关性（P(meta)=0.010，OR=0.77；95%置信区间 0.62-0.94）。比较研究之间的单倍群频率，我们注意到在美国和法国进行的研究之间存在很强的相似性，其中大多数男性携带 R1 单倍群，类似于西北欧人群。另一方面，芬兰人具有截然不同的单倍群分布，N1c 和 I1 单倍群占主导地位。总之，我们的研究结果表明，遗传 Y 染色体变异在欧洲人群的前列腺癌病因学中发挥有限作用，但需要在具有多种族背景的其他大型和特征良好的研究中进行随访。
