Reproductive Cancer Risk Factors in Women With Myotonic Dystrophy (DM): Survey Data From the US and UK DM Registries

Abstract

Introduction: Recent evidence demonstrates that women with myotonic dystrophy type 1 are at increased risk of reproductive organ tumors. However, studies of reproductive cancer risk factors in those patients are lacking.Methods: Using questionnaires, we collected and analyzed personal history information related to cancer risk factors from women enrolled in a UK and US registry for myotonic dystrophy (dystrophia myotonica; DM) patients.Results: The survey was completed by 242 DM type 1 (DM1) and 44 DM type 2 (DM2) women enrolled in the UK Registry (N = 124) and the US National Registry (N = 162). The mean age at DM1 diagnosis was 33.8 years (standard deviation, SD = 13.2) and for DM2 was 49.2 (SD = 13.0). Mean age at survey was 48.7 (SD = 12.8) and 59.1 years (SD = 12.8) for DM1 and DM2, respectively. There were no statistically significant differences between DM1 and DM2 regarding menstrual history or fertility-related factors. Yet, women with DM2 were more likely to have used menopausal hormone therapy (HT) than women with DM1 (52.3 vs. 22.1%, p < 0.0001), and more women with DM2 had a hysterectomy (53.5 vs. 29.5%, p < 0.01). These differences were not statistically significant after age adjustment (OR = 2.00, p = 0.08, and OR = 1.40, p = 0.38, respectively). The frequency of self-reported reproductive organ tumors was not significantly different comparing DM1 to DM2 (p = 0.28). However, the data suggested that women with DM2 appear to have a lower risk of malignant tumors compared to those with DM1 (OR = 0.72, p = 0.69).Discussion: Our study is the first to characterize a wide range of reproductive risk factors in women with DM. We observed no significant differences between DM1 and DM2 in the factors that were evaluated, which suggests that the known excesses of ovarian and endometrial cancer previously reported in women with DM1 cannot be attributed to greater prevalence of standard cancer-related reproductive risk factors. Larger studies evaluating the possible link between reproductive cancer risk factors and risk of tumors in women with DM are needed.

Cancer in myotonic dystrophy: A new discovery in an old disease

“…The findings by D'Ambrosio et al support the hypothesis that cancer in DM is linked to an underlying genetic predisposition. In line with this hypothesis, previous studies evaluating the possible contribution of known cancer risk factors to DM carcinogenesis found no evidence for a role for common risk factors such as smoking, obesity, or reproductive factors 12,13 . In addition, the noted multiple primary cancers, possible familial aggregation, and earlier age at onset for some cancer types, such as endometrial cancer, are all hallmarks of genetic cancer susceptibility 14,15 .…”

“…In line with this hypothesis, previous studies evaluating the possible contribution of known cancer risk factors to DM carcinogenesis found no evidence for a role for common risk factors such as smoking, obesity, or reproductive factors. 12,13 In addition, the noted multiple primary cancers, possible familial aggregation, and earlier age at onset for some cancer types, such as endometrial cancer, are all hallmarks of genetic cancer susceptibility. 14,15 Several possible molecular mechanisms have been suggested, including an upregulation of the Wnt/β-catenin signaling pathway supported by its high frequency in pilomatricoma, 16 an RNA-mediated defect in mismatch repair genes supported by the similarity of DM-cancer profile to that of Lynch syndrome, or a dysregulation in the miR-200 tumor suppressor family, increased cellular senescence, and impaired DNA machinery, all known mechanisms of cancer and recently detected in fibroblasts of patients with DM.…”

Hereditary gynecologic tumors and precision cancer medicine

“…Gynecological tumors, such as uterine myoma and ovarian cysts, are observed in >25% of patients, 129 with no significant differences between DM1 and DM2. The cancer mortality rate is 2.5 times higher 130 in carriers than in the general population, with gynecological tumors accounting for approximately 10% of deaths.…”

The current status of medical care for myotonic dystrophy type 1 in the national registry of Japan

“…Current treatment practices for the multisystemic issues associated with DM have not been fully characterized for the Japanese DM1 population. Disease registries have been used successfully to characterize the current care for DM patients worldwide 12–14 . In Japan, the Registry of Muscular Dystrophy (Remudy) is a national registry for various neuromuscular diseases 15,16 .…”

“…Disease registries have been used successfully to characterize the current care for DM patients worldwide. [12][13][14] In Japan, the Registry of Muscular Dystrophy (Remudy) is a national registry for various neuromuscular diseases. 15,16 In 2014, DM was registered as a disease in Remudy, and there are currently over 1,000 registered patients.…”