Talseth-Palmer Bente A, McPhillips Mary, Groombridge Claire, Spigelman Allan, Scott Rodney J
School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
Hered Cancer Clin Pract. 2010 May 21;8(1):5. doi: 10.1186/1897-4287-8-5.
Approximately 10% of Lynch syndrome families have a mutation in MSH6 and fewer families have a mutation in PMS2. It is assumed that the cancer incidence is the same in families with mutations in MSH6 as in families with mutations in MLH1/MSH2 but that the disease tends to occur later in life, little is known about families with PMS2 mutations. This study reports on our findings on mutation type, cancer risk and age of diagnosis in MSH6 and PMS2 families.
A total of 78 participants (from 29 families) with a mutation in MSH6 and 7 participants (from 6 families) with a mutation in PMS2 were included in the current study. A database of de-identified patient information was analysed to extract all relevant information such as mutation type, cancer incidence, age of diagnosis and cancer type in this Lynch syndrome cohort. Cumulative lifetime risk was calculated utilising Kaplan-Meier survival analysis.
MSH6 and PMS2 mutations represent 10.3% and 1.9%, respectively, of the pathogenic mutations in our Australian Lynch syndrome families. We identified 26 different MSH6 and 4 different PMS2 mutations in the 35 families studied. We report 15 novel MSH6 and 1 novel PMS2 mutations. The estimated cumulative risk of CRC at age 70 years was 61% (similar in males and females) and 65% for endometrial cancer in MSH6 mutation carriers. The risk of developing CRC is different between males and females at age 50 years, which is 34% for males and 21% for females.
Novel MSH6 and PMS2 mutations are being reported and submitted to the current databases for identified Lynch syndrome mutations. Our data provides additional information to add to the genotype-phenotype spectrum for both MSH6 and PMS2 mutations.
约10%的林奇综合征家族存在MSH6突变，而存在PMS2突变的家族更少。据推测，MSH6突变家族的癌症发病率与MLH1/MSH2突变家族相同，但疾病往往在较晚的年龄发生，而对于PMS2突变家族了解甚少。本研究报告了我们在MSH6和PMS2家族中关于突变类型、癌症风险及诊断年龄的研究结果。
本研究纳入了78名（来自29个家族）存在MSH6突变的参与者以及7名（来自6个家族）存在PMS2突变的参与者。分析了一个去识别化的患者信息数据库，以提取该林奇综合征队列中的所有相关信息，如突变类型、癌症发病率、诊断年龄和癌症类型。利用Kaplan-Meier生存分析计算累积终身风险。
在我们澳大利亚的林奇综合征家族中，MSH6和PMS2突变分别占致病突变的10.3%和1.9%。在研究的35个家族中，我们鉴定出26种不同的MSH6突变和4种不同的PMS2突变。我们报告了15种新的MSH6突变和1种新的PMS2突变。MSH6突变携带者在70岁时患结直肠癌的估计累积风险为61%（男性和女性相似），患子宫内膜癌的风险为65%。50岁时男性和女性患结直肠癌的风险不同，男性为34%，女性为21%。
正在报告新的MSH6和PMS2突变，并将其提交至当前已识别的林奇综合征突变数据库。我们的数据为MSH6和PMS2突变的基因型-表型谱增添了更多信息。
