Kerr Lynne, Rewhorn Matthew J, Longmuir Mark, Fraser Sioban, Walsh Shaun, Andrew Nicola, Leung Hing Y
Department of Urology, NHS Greater Glasgow and Clyde, Glasgow, G51 4TF, UK.
West of Scotland Genetic Service, Queen Elizabeth University Hospital, NHS Great Glasgow and Clyde, Glasgow, G51 4TF, UK.
BMC Cancer. 2016 Jul 25;16:529. doi: 10.1186/s12885-016-2573-x.
Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 %. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing.
Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies.
Overall 1 of 7 (14 %) and 1 of 20 (5 %) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 %) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis.
The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.
前列腺癌（PC）是全球男性主要的健康问题，估计终生风险约为14%。最近一项对突变过程的综合分析显示，衰老和错配修复是前列腺癌中唯一发生改变的过程。我们希望测试一组因BRCA1/2或林奇综合征突变而具有遗传性错配修复缺陷风险的男性是否为前列腺癌检测的目标人群。
邀请了58名来自有BRCA1/2或HNPCC/林奇突变家族史的男性（年龄在40 - 69岁之间）参与。推荐前列腺特异性抗原（PSA）>3.0 ng/ml的男性进行经直肠超声引导下的前列腺活检。
总体而言，携带BRCA1/2突变的男性中，7人中有1人（14%）前列腺癌诊断呈阳性，20人中有1人（5%）呈阳性。在林奇综合征男性中，4人中有1人（25%）被诊断患有前列腺癌。林奇综合征的索引病例在错配修复MSH6基因中存在杂合突变。前列腺肿瘤中MSH6免疫反应性几乎完全丧失，这支持了在前列腺癌发生过程中剩余MSH6等位基因的沉默。
在有林奇综合征家族史的受影响男性中发现MSH6表达几乎完全丧失，支持了其在前列腺癌发生过程中的机制性参与。因此，这项工作支持了这样的观点，即在某些男性人群中，林奇综合征突变在前列腺癌男性中具有生物学关联。
