Search

Risk of colorectal cancer (CRC) increases in relatives of patients with CRC. The extent to which this is attributable to genetic predisposition or shared environment is unclear. We explored this question using nationwide cohorts from Denmark, Finland and Sweden. From 1977 to 2013, we identified 359 879 individuals with a CRC diagnosis and 2 258 870 of their relatives who we followed for CRC incidence. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CI) for CRC in individuals with an affected relative. We used nationwide household and pedigree data along with national SIR estimates to calculate risk ratios (RR) for the contribution of shared household environment, childhood environment and genetic relationship to CRC risk in those with an affected relative. SIR of CRC was increased for individuals with an affected relative, across all countries and ages. For those with an affected parent, the SIR was 1.65 (95% CI: 1.61‐1.69), 1.98 (95% CI: 1.87‐2.09), for those with an affected sibling and 2.14 (95% CI: 1.84‐2.49) for those with an affected halfsibling. In those <65 years old, shared childhood (RR: 1.41, 95% CI: 1.26‐1.57) and household (RR: 2.08, 95% CI: 1.25‐3.46) environments were significantly greater contributors to familial risk of CRC than genetics (RR: 0.88, 95% CI: 0.53‐1.46). This large‐scale Nordic population‐based study of excess risk of CRC among relatives of those with CRC addresses the difficult disentangling of shared environment from genetic predisposition in the heritability of CRC. We found shared environment to be the most important contributor to CRC risk. [ABSTRACT FROM AUTHOR]

Context: Myotonic muscular dystrophy (MMD) is an autosomal-dominant multisystem neuromuscular disorder characterized by unstable nucleotide repeat expansions. Case reports have suggested that MMD patients may be at increased risk of malignancy, putative risks that have never been quantified., Objective: To quantitatively evaluate cancer risk in patients with MMD, overall and by sex and age., Design, Setting, and Participants: We identified 1658 patients with an MMD discharge diagnosis in the Swedish Hospital Discharge Register or Danish National Patient Registry between 1977 and 2008. We linked these patients to their corresponding cancer registry. Patients were followed up from date of first MMD-related inpatient or outpatient contact to first cancer diagnosis, death, emigration, or completion of cancer registration., Main Outcome Measures: Risks of all cancers combined and by anatomic site, stratified by sex and age., Results: One hundred four patients with an inpatient or outpatient discharge diagnosis of MMD developed cancer during postdischarge follow-up. This corresponds to an observed cancer rate of 73.4 per 10,000 person-years in MMD vs an expected rate of 36.9 per 10,000 person-years in the general Swedish and Danish populations combined (standardized incidence ratio [SIR], 2.0; 95% CI, 1.6-2.4). Specifically, we observed significant excess risks of cancers of the endometrium (n = 11; observed rate, 16.1/10,000 person-years; SIR, 7.6; 95% CI, 4.0-13.2), brain (n = 7; observed rate, 4.9/10,000 person-years; SIR, 5.3; 95% CI, 2.3-10.4), ovary (n = 7; observed rate, 10.3/10,000 person-years; SIR, 5.2; 95% CI, 2.3-10.2), and colon (n = 10; observed rate, 7.1/10,000 person-years; SIR, 2.9; 95% CI, 1.5-5.1). Cancer risks were similar in women and men after excluding genital organ tumors (SIR, 1.9; 95% CI, 1.4-2.5, vs SIR, 1.8; 95% CI, 1.3-2.5, respectively; P = .81 for heterogeneity; observed rates, 64.5 and 47.7 per 10,000 person-years in women and men, respectively). The same pattern of cancer excess was observed first in the Swedish and then in the Danish cohorts, which were studied sequentially and initially analyzed independently., Conclusion: Patients with MMD identified from the Swedish and Danish patient registries were at increased risk of cancer both overall and for selected anatomic sites.