The spectrum of urological malignancy in Lynch syndrome
The spectrum of urological malignancy in Lynch syndrome
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DOI：
10.1007/s10689-012-9573-z
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发表时间：
2013-03-01
期刊：
影响因子：
2.2
通讯作者：
Evans, D. G.
中科院分区：
文献类型：
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作者：
Barrow, P. J.;Ingham, S.;Evans, D. G.
在林奇综合征中，泌尿系统肿瘤是继结肠癌和子宫内膜癌之后第三常见的恶性肿瘤。上尿路肿瘤在林奇综合征中已得到充分认识，但与前列腺癌和膀胱癌的关联存在争议。我们确定了一组林奇综合征家族中前列腺癌和膀胱癌的发病率、累积风险和相对风险。从曼彻斯特地区林奇综合征数据库（n = 821）中确定了男性林奇综合征突变携带者及其未经基因检测的男性一级亲属（FDR）。确定了每个泌尿系统部位（肾盂、输尿管、膀胱和前列腺）发生泌尿系统癌症的时间。计算了累积风险和相对风险，并根据突变携带者状态和特定致病基因突变对结果进行分类。共发现8例前列腺癌，只有1例发生在60岁之前。按林奇综合征突变携带者状态对前列腺癌发病风险人年的分析表明，MSH2突变携带者与前列腺癌风险增加10倍相关（相对风险RR为10.41；95%置信区间为2.80 - 26.65）。未发现与膀胱癌有此类关联（RR为1.88；95%置信区间为0.21 - 6.79）。上尿路肿瘤与MSH2和MLH1突变的关联得到了证实。我们对男性林奇综合征突变携带者进行了最大规模的研究，以确定泌尿系统恶性肿瘤的风险。MSH2突变携带者前列腺癌风险增加10倍得到支持，其患前列腺癌的风险大约是一级亲属的两倍。对40 - 50岁的MSH2携带者进行前列腺特异性抗原（PSA）检测试验可能是合理的。
Urological tumours are the third most frequent malignancy in Lynch syndrome after colonic and endometrial cancer. Upper urinary tract tumours are well recognised in Lynch syndrome, but the association with prostate and bladder cancer is controversial. We determined the incidence and cumulative and relative risks of prostate and bladder cancer in a cohort of Lynch syndrome families. Male Lynch syndrome mutation carriers and their genetically untested male first degree relatives (FDR) were identified from the Manchester Regional Lynch syndrome database (n = 821). Time to the development of urological cancer was identified for each urological site (renal pelvis, ureter, bladder and prostate). Cumulative and relative risks were calculated, with results classified by mutation carrier status and specific causative genetic mutations. Eight prostate cancers were identified, only one occurring before the age of 60. Analysis of person-years at risk of prostate cancer by Lynch syndrome mutation carrier status suggests a correlation between MSH2 mutation carriers and a tenfold increased risk of prostate cancer (RR 10.41; 95 % CI 2.80, 26.65). No such association was found with bladder cancer (RR 1.88; 95 % CI 0.21, 6.79). The association of upper urinary tract tumours with MSH2 and MLH1 mutations was confirmed. We have carried out the largest study of male Lynch syndrome mutation carriers to establish the risks of urological malignancy. A tenfold increased risk of prostate cancer is supported in MSH2 with mutation carriers having roughly double the risk of prostate cancer to FDRs. A trial of PSA testing in MSH2 carriers from 40 to 50 years may be justifiable.