Lund M, Diaz L J, Gørtz S, Feenstra B, Duno M, Juncker I, Eiberg H, Vissing J, Wohlfahrt J, Melbye M
Department of Epidemiology Research, National Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
Eur J Neurol. 2014 Sep;21(9):1192-7. doi: 10.1111/ene.12466. Epub 2014 May 17.
Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted.
DM was identified using the National Danish Patient Registry and results of genetic testing. Information on cancer was obtained from the Danish Cancer Registry. A population-based cohort of 5 757 565 individuals with at least one relative was established using the Danish Family Relations Database based on kinship links in the Danish Civil Registration System. Familial aggregation of cancer was evaluated by (incidence) rate ratios (RRs) comparing the rate of cancer amongst relatives of patients with DM from 1977 to 2010 (exposed) with the rate of cancer amongst persons with a relative of the same type but without DM (non-exposed).
In first-degree relatives of individuals with DM the adjusted RR of cancer was 0.89 (95% confidence interval 0.71-1.12) overall, and in stratified analyses 0.68 (0.37-1.12) before age 50 and 0.96 (0.74-1.23) at age 50 or older.
The present study does not support an increased risk of cancer in non-DM relatives of DM patients suggesting that cancer and DM are associated through derived effects of the DM genotype.
强直性肌营养不良症（DM）是由不稳定的核苷酸重复扩增引起的常染色体显性遗传神经肌肉疾病。DM与癌症有关联，但两者关联背后的发病机制仍不清楚。这可能与DM基因型的衍生效应有关，在这种情况下，DM患者的非DM亲属患癌风险预计不会增加。为阐明这一点，开展了一项基于人群的队列研究，调查DM患者亲属的患癌风险。
利用丹麦国家患者登记处的数据和基因检测结果来识别DM。癌症信息来自丹麦癌症登记处。基于丹麦民事登记系统中的亲属关系链接，使用丹麦家庭关系数据库建立了一个包含5757565名至少有一名亲属的人群队列。通过发病率比（RRs）评估癌症的家族聚集性，比较1977年至2010年DM患者亲属（暴露组）的癌症发病率与有相同类型亲属但无DM的人群（非暴露组）的癌症发病率。
DM患者一级亲属的癌症校正RR总体为0.89（95%置信区间0.71 - 1.12），分层分析显示，50岁前为0.68（0.37 - 1.12），50岁及以上为0.96（0.74 - 1.23）。
本研究不支持DM患者的非DM亲属患癌风险增加，这表明癌症与DM是通过DM基因型的衍生效应相关联的。
