1型糖尿病的癌症风险与性别相关，并与miRNA - 200/141下调有关。

Cancer risk in DM1 is sex-related and linked to miRNA-200/141 downregulation.

作者信息

Fernández-Torrón Roberto, García-Puga Mikel, Emparanza José-Ignacio, Maneiro Miren, Cobo Ana-María, Poza Juan-José, Espinal Juan-Bautista, Zulaica Miren, Ruiz Irune, Martorell Loreto, Otaegui David, Matheu Ander, López de Munain Adolfo

机构信息

From the Neuromuscular Unit, Neurology Department (R.F.-T., M.M., J.-J.P., J.-B.E., A.L.d.M.), and Department of Pathology (I.R.), Donostia Universitary Hospital, San Sebastian; Neurosciences Area (R.F.-T., M.Z., D.O., A.L.d.M.) and Oncology Area (M.G.-P., A.M.), Biodonostia Institute, San Sebastian; Center for Biomedical Research Network in Neurodegenerative Diseases (CIBERNED) (R.F.-T., A.L.d.M.), Institute Carlos III, Ministry of Economy and Competitiveness; Clinical Epidemiology Unit (J.-I.E.), Donostia Universitary Hospital, CIBER-ESP, San Sebastian, Spain; Neuromuscular Area (A.-M.C.), AP-HP Hôpital Marin de Hendaye, France; Molecular Genetics Section (L.M.), Hospital Sant Joan de Deu, Barcelona; and Department of Neurosciences (A.L.d.M.), University of the Basque Country, UPV/EHU, San Sebastian, Spain.

出版信息

Neurology. 2016 Sep 20;87(12):1250-7. doi: 10.1212/WNL.0000000000003124. Epub 2016 Aug 24.

DOI:10.1212/WNL.0000000000003124

PMID:27558368

Abstract

OBJECTIVE

Describe the incidence of cancer in a large cohort of patients with myotonic dystrophy type 1 (DM1) and to unravel the underlying molecular mechanisms.

METHODS

Standardized incidence ratios (SIRs) were calculated in the Gipuzkoa DM1 cohort (1985-2013), dividing observed numbers by expected numbers for all cancers combined and stratified by sex. An estimation of the expected incidence was achieved by multiplying the age- and sex-specific incidence rates from the Basque population cancer registry by the person-years observed in the study cohort. Large-scale gene expression of peripheral blood mononuclear cell samples derived from 10 individuals with DM1 (5 men, 5 women) and 10 healthy matched controls was analyzed by the Human Gene 1.0 ST Affymetrix microarray.

RESULTS

During 18,796 person-years of follow-up, corresponding to 424 patients with DM1, we observed 70 cancers in 62 patients giving a 1.81-fold risk (95% confidence interval [CI] 1.37-2.36), which was stronger in women than in men. Ovary (SIR 8.33, 95% CI 1.72-24.31) and endometrium (SIR 6.86, 95% CI 2.23-16.02) in women and thyroid (SIR 23.33, 95% CI 9.38-48.08) and brain (SIR 9.80, 95% CI 3.18-22.88) in both sexes were tumor sites with significantly higher risks in DM1. There were differences in gene expression between healthy controls and patients with DM1 and between men and women with DM1; all patients with DM1 combined and female patients with DM1 displayed significant downregulation of the microRNA (miRNA)-200c/141 tumor suppressor family.

CONCLUSIONS

Oncologic risk is increased in DM1, especially in women and for gynecologic, brain, and thyroid cancer. Expression of the miRNA-200/miRNA-141 tumor suppressor family is decreased in women with DM1.

摘要

目的

描述1型强直性肌营养不良（DM1）患者大群体中的癌症发病率，并阐明潜在的分子机制。

方法

在吉普斯夸DM1队列（1985 - 2013年）中计算标准化发病比（SIR），将所有癌症合并后的观察数除以预期数，并按性别分层。通过将巴斯克人群癌症登记处的年龄和性别特异性发病率乘以研究队列中观察到的人年数来估计预期发病率。使用人类基因1.0 ST Affymetrix微阵列分析来自10名DM1患者（5名男性，5名女性）和10名健康匹配对照的外周血单个核细胞样本的大规模基因表达。

结果

在18796人年的随访期间，对应424名DM1患者，我们在62名患者中观察到70例癌症，风险增加1.81倍（95%置信区间[CI] 1.37 - 2.36），女性的风险高于男性。女性中的卵巢（SIR 8.33，95% CI 1.72 - 24.31）和子宫内膜（SIR 6.86，95% CI 2.23 - 16.02）以及两性中的甲状腺（SIR 23.33，95% CI 9.38 - 48.08）和脑（SIR 9.80，9% CI 3.18 - 22.88）是DM1中风险显著更高的肿瘤部位。健康对照与DM1患者之间以及DM1男性和女性之间存在基因表达差异；所有合并的DM1患者和DM1女性患者均显示微小RNA（miRNA）-200c/141肿瘤抑制家族显著下调。