Kotsopoulos Joanne, Sopik Victoria, Rosen Barry, Fan Isabel, McLaughlin John R, Risch Harvey, Sun Ping, Narod Steven A, Akbari Mohammad R
Women's College Research Institute, Women's College Hospital, 76 Grenville St, 6th Floor, Room# 6421, Toronto, ON, M5S 1B2, Canada.
Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada.
Fam Cancer. 2017 Jan;16(1):29-34. doi: 10.1007/s10689-016-9919-z.
Recent studies suggest that mutations in the partner and localizer of BRCA2 (PALB2) gene may predispose to ovarian cancer. It is of importance to clarify the prevalence and penetrance of PALB2 mutations in an unselected population so that clinical recommendations for prevention can be implemented. We evaluated the prevalence of germline mutations in PALB2 among 1421 epithelial ovarian cancer patients and 4300 European controls from the National Heart, Lung, and Blood Institute's Exome Sequencing Project dataset. Clinical information was obtained from medical records and survival status was determined by linkage. PALB2 coding exons were sequenced using next generation sequencing technology. Of the 1421 patients, three (0.21 %) had a germline PALB2 mutation compared to two of the 4300 control subjects (0.05 %). The mean age at diagnosis was 59 years (range 55-62) and all three women died within 2 years of diagnosis. A PALB2 mutation was associated with a four-fold, albeit not significant, increased risk of ovarian cancer (OR = 4.55; 95 % CI 0.76-27.24; P = 0.10). These results suggest that germline PALB2 mutations are rare. The true effect of such mutations on ovarian cancer risk require further study before the clinical relevance of inherited PALB2 mutations is established.
近期研究表明，乳腺癌2号基因伴侣及定位蛋白（PALB2）基因的突变可能易患卵巢癌。明确未经过选择的人群中PALB2突变的患病率及外显率，对于实施预防的临床建议至关重要。我们从美国国立心肺血液研究所外显子测序项目数据集中评估了1421例上皮性卵巢癌患者及4300例欧洲对照人群中PALB2种系突变的患病率。临床信息从病历中获取，生存状态通过关联确定。采用新一代测序技术对PALB2编码外显子进行测序。在1421例患者中，有3例（0.21%）存在种系PALB2突变，而4300例对照人群中有2例（0.05%）。诊断时的平均年龄为59岁（范围55 - 62岁），所有3名女性均在诊断后2年内死亡。PALB2突变与卵巢癌风险增加4倍相关，尽管不显著（OR = 4.55；95% CI 0.76 - 27.24；P = 0.10）。这些结果表明种系PALB2突变罕见。在确定遗传性PALB2突变的临床相关性之前，此类突变对卵巢癌风险的真正影响需要进一步研究。
