Karimi Masoud, von Salomé Jenny, Aravidis Christos, Silander Gustav, Askmalm Marie Stenmark, Henriksson Isabelle, Gebre-Medhin Samuel, Frödin Jan-Erik, Björck Erik, Lagerstedt-Robinson Kristina, Lindblom Annika, Tham Emma
1Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
2Department of Clinical Genetics, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden.
Hered Cancer Clin Pract. 2018 Oct 23;16:16. doi: 10.1186/s13053-018-0098-9. eCollection 2018.
Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes or . 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.
Data 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.
A total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in and comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.
Lynch 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 -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.
林奇综合征是一种常染色体显性癌症综合征，由DNA错配修复（MMR）基因之一的致病种系变异引起。携带者易患结直肠癌和子宫内膜癌，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。
数据来自瑞典六个医疗保健区域中五个区域的235个经基因验证的林奇家族。材料按性别、原发性癌症、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普通人群进行比较。
共有1053名家庭成员被诊断出患有1493例癌症，其中1011例为结直肠癌或子宫内膜癌。携带 和 致病变体的个体占队列的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， 携带者的泌尿系统、胃癌、小肠癌、卵巢癌和非黑色素瘤皮肤癌比例显著增加。 携带者的胃肠道癌症（胃癌、小肠癌、胰腺癌）比例升高，而 携带者的卵巢癌比预期的多。胃癌主要在老一辈中出现。
林奇综合征会增加患结直肠癌和子宫内膜癌以外的多种癌症的风险。不同MMR基因导致的其他癌症比例有所不同， 携带者中出现的频率最高。性别和年龄也会影响肿瘤谱，这表明在确定不同癌症类型的易感性方面，其他环境和体质参数也很重要。
