Risk of breast cancer in Lynch syndrome: a systematic review.
Risk of breast cancer in Lynch syndrome: a systematic review.
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DOI：
10.1186/bcr3405
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发表时间：
2013-03-19
期刊：
影响因子：
--
通讯作者：
Jenkins MA
中科院分区：
文献类型：
--
作者：
Win AK;Lindor NM;Jenkins MA
Lynch综合征是一种常染色体显性遗传的癌症易感性疾病，由DNA错配修复（MMR）基因的种系突变引起。突变携带者有结肠癌、直肠癌、子宫内膜癌和其他几种器官癌风险增加的重大负担，这些癌症通常发生在比一般人群更年轻的年龄。MMR基因突变携带者患乳腺癌的风险是否会增加，这一问题一直在争论，支持和反对这种关联的证据。使用PUBMED，我们确定了截至2012年12月15日发表的与Lynch综合征相关的所有乳腺癌相关研究。在综述中，我们包括：（i）分子研究，报告微卫星不稳定性和/或免疫组化在乳腺癌肿瘤的MMR基因突变携带者;和（ii）风险研究，调查乳腺癌的风险确认MMR基因突变携带者或家庭或临床和/或病理定义的林奇综合征家庭。我们确定了15项分子研究，当合并时，观察到122例（51%; 95%CI 42 - 60%）MMR基因突变携带者乳腺癌中有62例MMR缺陷。在确定的21项风险研究中，13项没有观察到乳腺癌风险与Lynch综合征相关的统计学证据，而8项研究发现，与普通人群（或非携带者）相比，乳腺癌风险增加2至18倍。只有一项前瞻性研究表明，与一般人群相比，MMR基因突变携带者患乳腺癌的风险升高（标准化发病率比3.95; 95% CI 1.59，8.13）。由于乳腺癌在一般人群中是一种相对常见的疾病，因此需要利用长期随访的大型前瞻性队列研究来更精确地估计风险和基因特异性风险。虽然目前的数据在人群水平上尚不确定，但个体肿瘤检测结果表明，MMR缺乏症与一些Lynch综合征患者的乳腺癌有关。
Lynch syndrome is an autosomal dominantly inherited disorder of cancer susceptibility caused by germline mutations in the DNA mismatch repair (MMR) genes. Mutation carriers have a substantial burden of increased risks of cancers of the colon, rectum, endometrium and several other organs which generally occur at younger ages than for the general population. The issue of whether breast cancer risk is increased for MMR gene mutation carriers has been debated with evidence for and against this association. Using the PUBMED, we identified all relevant studies of breast cancer associated with Lynch syndrome that were published by 15 December 2012. In the review, we included: (i) molecular studies that reported microsatellite instability and/or immunohistochemistry in breast cancer tumors of MMR gene mutation carriers; and (ii) risk studies that investigated risk of breast cancer for confirmed MMR gene mutation carriers or families or clinically and/or pathologically defined Lynch syndrome families. We identified 15 molecular studies and, when combined, observed 62 of 122 (51%; 95% CI 42 to 60%) breast cancers in MMR gene mutation carriers were MMR-deficient. Of the 21 risk studies identified, 13 did not observe statistical evidence for an association of breast cancer risk with Lynch syndrome while 8 studies found an increased risk of breast cancer ranging from 2- to 18-fold compared with the general population (or non-carriers). There is only one prospective study demonstrating an elevated risk of breast cancer for MMR gene mutation carriers compared with the general population (standardized incidence ratio 3.95; 95% CI 1.59, 8.13). Since breast cancer is a relatively common disease in the general population, more precise estimates of risk and gene-specific risks will need to utilize large prospective cohort studies with a long follow-up. While current data are inconclusive at a population level, individual tumor testing results suggest that MMR deficiency is involved with breast cancers in some individuals with Lynch syndrome.
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