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Alsaggaf, Rotana; St. George, Diane Marie M; Zhan, Min; Pfeiffer, Ruth M; Wang, Youjin; Wagner, Kathryn R; Greene, Mark H; Amr, Sania; Gadalla, Shahinaz M
JNCI cancer spectrum, 10/2018, Letnik: 2, Številka: 4Journal Article
Abstract Background Myotonic dystrophy type 1 (DM1) is an inherited trinucleotide repeat disorder in which specific cancers have been implicated as part of the disease phenotype. This study aimed to assess whether cancer risk in DM1 patients is modified by disease severity. Methods Using the United Kingdom Clinical Practice Research Datalink (primary care electronic medical records), we identified a cohort of 927 DM1 and a matched cohort of 13 085 DM1-free individuals between January 1, 1988 and February 29, 2016. We used Cox regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of organ-specific cancer risks. Analyses were stratified by age at DM1 diagnosis as a surrogate for disease severity. Statistical tests were two-sided. Results Patients with classic DM1 (age at diagnosis: 11–40 years) were at elevated risk of cancer overall (HR = 1.81; 95% CI = 1.12 to 2.93); cancers of the thyroid (HR = 15.93; 95% CI = 2.45 to 103.64), uterus (HR = 26.76; 95% CI = 2.32 to 309.26), and cutaneous melanoma (HR = 5.98; 95% CI = 1.24 to 28.79) accounted for the excess. In late-onset DM1 patients (age at diagnosis >40 years), a reduced overall cancer risk was observed (HR = 0.53; 95% CI = 0.32 to 0.85), possibly driven by the deficit in hematological malignancies (DM1 = 0 cases, DM1-free = 54 cases; P = .02). The difference between the observed HR for classic and late-onset DM1 was statistically significant (P < .001). Conclusions The observed difference in relative cancer risk between classic and late-onset DM1 patients compared with their DM1-free counterparts provides the first evidence that disease severity modifies DM1-related cancer susceptibility. This novel finding may guide clinical management and scientific investigations for the underlying molecular mechanisms in DM-related carcinogenesis.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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