BackgroundLynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.MethodsData were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population.ResultsA total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.ConclusionLynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.

中文翻译：

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瑞典林奇综合征家族结肠外非子宫内膜癌的回顾性研究

背景林奇综合征是一种常染色体显性遗传癌症综合征，由 DNA 错配修复 (MMR) 基因 MLH1、MSH2、MSH6 或 PMS2 之一的致病性种系变异引起。携带者易患结直肠癌和子宫内膜癌，但也易患其他癌症类型。这项回顾性研究的目的是描述瑞典林奇综合征家族的肿瘤谱。方法数据来自瑞典六个医疗保健地区中的五个经过基因验证的 235 个林奇家族。该材料按性别、原发癌症、年龄和突变基因进行分层，并将特定癌症类型的相对比例与一般人群进行比较。结果共有1053名家庭成员诊断出癌症1493例，其中1011例为结直肠癌或子宫内膜癌。具有 MLH1 和 MSH2 致病性变异的个体占队列的 78%。在 482 例非结直肠癌/非子宫内膜癌诊断中，与正常人群相比，MSH2 携带者的泌尿道癌、胃癌、小肠癌、卵巢癌和非黑色素瘤皮肤癌的比例显着增加。MLH1 携带者的胃肠道癌症（胃癌、小肠、胰腺）比例升高，而 MSH6 携带者的卵巢癌比例高于预期。胃癌主要发生在老一代人身上。结论Lynch 综合征会增加患多种癌症的风险，而不是结直肠癌和子宫内膜癌。其他癌症的比例因不同的 MMR 基因而异，在 MSH2 携带者中频率最高。性别和年龄也会影响肿瘤谱，