Causes of death of mutation carriers in Finnish Lynch syndrome families
Causes of death of mutation carriers in Finnish Lynch syndrome families
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DOI：
10.1007/s10689-012-9537-3
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发表时间：
2012-09-01
期刊：
影响因子：
2.2
通讯作者：
Mecklin, Jukka-Pekka
中科院分区：
文献类型：
--
作者：
Pylvanainen, Kirsi;Lehtinen, Tuula;Mecklin, Jukka-Pekka
林奇综合征(LS)是一种常染色体显性遗传癌症综合征，包括结直肠癌(CRC)和子宫内膜癌(EC)的终身风险增加，但也包括其他类型的癌症。结直肠癌的风险高达70%-80%，结直肠癌高达50%-60%。由于筛查和早期诊断，与结直肠癌和EC相关的死亡率似乎很低。尽管有很多关于突变携带者监测的研究，但还没有对LS家系的死亡原因进行全面的评估。利用医院记录和相关国家登记，对所有已故的、经检测的突变携带者及其突变阴性亲属(N=179)的病史和死亡原因进行检查。在1069名突变携带者中，有151人死亡；97人(%)死于癌症。在1146个突变阴性的家庭中，有44名成员死亡，其中11人(25%)死于癌症。在死亡的突变携带者中，有12人(7.7%)没有被诊断出癌症。死于癌症的平均年龄为63.2岁，而非癌症原因的平均死亡年龄为68.8岁。仅7.9%的结直肠癌患者死于结直肠癌，5%的结直肠癌患者死亡。61%的癌症死亡与结肠癌和子宫内膜外癌症有关。与Mut家族成员相比，Mut+患者的累积总体死亡率和癌症特异性死亡率显著增加。即使监测结果降低了LS中最常见的癌症CRC和EC的终身风险和死亡率，几乎所有突变携带者都会感染癌症，三分之二的死者已死于癌症。在遗传咨询中应该考虑到这一点。应鼓励突变携带者在出现异常症状时寻求帮助。
Lynch syndrome (LS) is an autosomal dominant cancer syndrome including increased life-long risk for colorectal (CRC) and endometrial (EC) cancer, but also for cancers of other types. The risk for CRC is up to 70-80 % and for EC up to 50-60 %. Due to screening and early diagnosing the mortality related to CRC and EC seems to be low. In spite of many studies on surveillance of mutation carriers, there is no comprehensive evaluation on causes of death in LS families. The disease history and cause of death of all the deceased, tested mutation carriers and their mutation negative relatives in the Finnish LS families (N = 179) was examined utilizing hospital records and relevant national registries. Out of 1069 mutation carriers 151 had succumbed; 97 (64 %) from cancer. Out of 1146 mutation-negative family 44 members had died; 11 (25 %) of them from cancer. In 12 (7.7 %) of the deceased mutation carriers no cancer had been diagnosed. The mean age of death from cancer was 63.2 years vs. 68.8 years from non-cancer causes. Only 7.9 % of the patients with CRC had died from CRC and 5 % of those with EC, respectively. 61 % of the cancer deaths were related to extra-colonic, extra-endometrial cancers. The cumulative overall and cancer specific death rates were significantly increased in Mut+ compared to Mut- family members. Even surveillance yields decrease in the life-long risk and mortality of the most common cancers CRC and EC in LS, almost all mutation carriers will contract with cancer, and two thirds of the deceased have died from cancer. This should be taken in account in genetic counseling. Mutation carriers should be encouraged to seek help for abnormal symptoms.