ZIA CP010144 10568 (ZIA) | |||
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Title | Cancer Risk in Myotonic Dystrophy | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Gadalla, Shahinaz | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $153,082 | Project Dates | null - null |
Fiscal Year | 2018 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) Cancer Survivorship (100.0%) |
Brain (20.0%) Colon/Rectum (20.0%) Eye (5.0%) Ovarian Cancer (20.0%) Uterine (20.0%) |
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Research Type | |||
Exogenous Factors in the Origin and Cause of Cancer Endogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
We conducted the first epidemiological investigation to determine whether myotonic dystrophy, the most common inherited adult muscle dystrophy, includes an increased risk of malignancy as part of its phenotype. We found a highly-significant excess risk of cancer in myotonic dystrophy patients first in Sweden, and then replicated in Denmark. Colon, ovarian, endometrial, and brain cancer drove these findings (JAMA 2011; 306:2480). Next, we analyzed myotonic dystrophy patients enrolled in the National Myotonic Dystrophy Registry. Our analyses indicated that female gender and myotonic dystrophy type1 are associated with excess risk of tumors (J Neurol 2012; 259:2161). We then calculated estimates of absolute cancer risk and cancer mortality, accounting for the high non-cancer competing mortality associated with DM (PloS One 2013; 8(11):e79851, Epub). Absolute cancer risk after DM diagnosis was 1.6%, 5% and 9% at ages 40, 50 and 60 years, respectively. Females had a higher absolute risk of all cancers combined than males: 9% and 13% vs. 2% and 4% by ages 50 and 60 years, respectively, and developed cancer at younger ages (median age =51 years vs. 57 years, p=0.02). Cancer deaths accounted for 10% of all deaths, with an absolute cancer mortality risk of 2%, 4%, and 6% by ages 50, 60, and 70 years, respectively. No gender difference in cancer-specific mortality was observed (p=0.6). Thus, cancer significantly contributed to morbidity and mortality in DM patients, even after accounting for high competing DM mortality from non-neoplastic causes. It is important to apply population-appropriate, validated cancer screening strategies in DM patients. Our current and future studies aim at confirming these observations, and determining the clinical predictors, and the biological mechanisms, of carcinogenesis in those patients, through collaborations with the U of Rochester, UK DM Registry, the UK Clinical Practice Research Datalink and the Rome DM Registry. |