Machiela Mitchell J, Dagnall Casey L, Pathak Anand, Loud Jennifer T, Chanock Stephen J, Greene Mark H, McGlynn Katherine A, Stewart Douglas R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
J Hum Genet. 2017 Jun;62(6):637-640. doi: 10.1038/jhg.2017.20. Epub 2017 Mar 9.
Studies have suggested mosaic loss of chromosome Y (mLOY) in blood-derived DNA is common in older men. Cohort studies investigating mLOY and mortality have reported contradictory results. Previous work found that a 1.6 Mb deletion of the AZFc region on the Y chromosome (the 'gr/gr' deletion) is associated with both male infertility and increased risk of testicular germ cell tumors (TGCT). We investigated whether mosaic loss across the entire Y chromosome was associated with TGCT. We obtained blood- and buccal-derived DNA from two case-control studies: the NCI Familial Testicular Cancer Study (cases=172; controls=163) and the NCI US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study (cases=506; controls=611). We used 15 quantitative polymerase chain reactions spanning the Y chromosome to assess mLOY. Multivariate logistic regression models adjusted for study batch effects detected no significant overall relationship between mean chromosome Y target-to-reference (T/R) ratio and TGCT (odds ratio=0.34, 95% confidence interval=0.10-1.17, P=0.09). When restricted to familial TGCT cases, a significantly lower T/R ratio was observed in cases compared with controls (0.993 vs 1.014, P-value=0.01). Our study suggests that mLOY, as measured by 15 probes spanning the Y chromosome, could be associated with familial TGCT, but larger studies are required to confirm this observation.
研究表明，老年男性血液来源的DNA中Y染色体镶嵌性缺失（mLOY）很常见。调查mLOY与死亡率的队列研究报告了相互矛盾的结果。先前的研究发现，Y染色体上AZFc区域1.6 Mb的缺失（“gr/gr”缺失）与男性不育以及睾丸生殖细胞肿瘤（TGCT）风险增加有关。我们调查了整个Y染色体的镶嵌性缺失是否与TGCT有关。我们从两项病例对照研究中获取了血液和口腔来源的DNA：美国国立癌症研究所家族性睾丸癌研究（病例=172；对照=163）和美国国立癌症研究所美国军人睾丸肿瘤环境与内分泌决定因素研究（病例=506；对照=611）。我们使用了15个跨越Y染色体的定量聚合酶链反应来评估mLOY。针对研究批次效应进行调整的多变量逻辑回归模型未检测到平均染色体Y目标与参照（T/R）比率与TGCT之间存在显著的总体关系（优势比=0.34，95%置信区间=0.10-1.17，P=0.09）。当仅限于家族性TGCT病例时，与对照组相比，病例组的T/R比率显著更低（0.993对1.014，P值=0.01）。我们的研究表明，通过跨越Y染色体的15个探针测量的mLOY可能与家族性TGCT有关，但需要更大规模的研究来证实这一观察结果。
