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Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study.

ABSTRACT: A balanced robertsonian translocation (rob) results from fusion of 2 acrocentric chromosomes. Carriers are phenotypically normal and are often diagnosed because of recurrent miscarriages, infertility, or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. We followed 1,987 carriers diagnosed in Great Britain for deaths and cancer risk, over an average of 24.1 years. Standardized mortality and incidence ratios were calculated comparing the number of observed events against population rates. Overall mortality was higher for carriers diagnosed before age 15 years (standardized mortality ratio (SMR) = 2.00, 95% confidence interval (CI): 1.09, 3.35), similar for those diagnosed aged 15-44 years (SMR = 1.06, 95% CI: 0.86-1.28), and lower for those diagnosed aged 45-84 years (SMR = 0.81, 95% CI: 0.68, 0.95). Cancer incidence was higher for non-Hodgkin lymphoma (standardized incidence ratio (SIR) = 1.90, 95% CI: 1.01, 3.24) and childhood leukemia (SIR = 14.5, 95% CI: 1.75, 52.2), the latter particularly in rob(15;21) carriers (SIR = 447.8, 95% CI: 11.3, 2,495). Rob(13;14) carriers had a higher breast cancer risk (SIR = 1.58, 95% CI: 1.12, 2.15). Mortality risks relative to the population in diagnosed carriers depend on age at cytogenetic diagnosis, possibly reflecting age-specific cytogenetic referral reasons. Carriers might be at greater risk of childhood leukemia and non-Hodgkin lymphoma and those diagnosed with rob(13;14) of breast cancer.

SUBMITTER: Schoemaker MJ

PROVIDER: S-EPMC6395160 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study.

Schoemaker Minouk J MJ Jones Michael E ME Higgins Craig D CD Wright Alan F AF Swerdlow Anthony J AJ

American journal of epidemiology 20190301 3

A balanced robertsonian translocation (rob) results from fusion of 2 acrocentric chromosomes. Carriers are phenotypically normal and are often diagnosed because of recurrent miscarriages, infertility, or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. We followed 1,987 carriers diagnosed in Great Britain for deaths and cancer risk, over an average of 24.1 years. Standardized mortality and incidence ratios were calculated compari ...[more]

PMID: 30535276

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Project description:ImportanceDiabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.ObjectiveTo evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.Design, setting, and participantsThis cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524?089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.ExposuresIncident cancer (time-varying exposure).Main outcomes and measuresIncident type 2 diabetes using insurance claim codes.ResultsDuring 3?492?935.6 person-years of follow-up (median follow-up, 7.0 years) in 494?189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15?130 participants developed cancer and 26?610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P?<?.001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.Conclusions and relevanceIn this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.

Project description:BackgroundSeveral health agencies have issued guidelines promoting behaviors to reduce chronic disease risk; however, little is known about the impact of such guidelines, particularly on cancer incidence.ObjectiveThe objective was to determine whether greater adherence to the American Cancer Society (ACS) cancer prevention guidelines is associated with a reduction in cancer incidence, cancer mortality, and total mortality.DesignThe NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults aged 50-71 y at recruitment in 1995-1996, was followed for a median of 10.5 y for cancer incidence, 12.6 y for cancer mortality, and 13.6 y for total mortality. Participants who reported a history of cancer or who had missing data were excluded, yielding 476,396 subjects for analysis. We constructed a 5-level score measuring adherence to ACS guidelines, which included baseline body mass index, physical activity, alcohol intake, and several aspects of diet. Cox proportional hazards models were used to compute HRs and 95% CIs for the association of the adherence score with cancer incidence, cancer mortality, and total mortality. All analyses included fine adjustment for cigarette smoking.ResultsAmong 476,396 participants, 73,784 incident first cancers, 16,193 cancer deaths, and 81,433 deaths from all causes were identified in the cohort. Adherence to ACS guidelines was associated with reduced risk of all cancers combined: HRs (95% CIs) for the highest compared with the lowest level of adherence were 0.90 (0.87, 0.93) in men and 0.81 (0.77, 0.84) in women. Fourteen of 25 specific cancer sites showed a reduction in risk associated with increased adherence. Adherence was also associated with reduced cancer mortality [HRs (95% CIs) were 0.75 (0.70, 0.80) in men and 0.76 (0.70, 0.83) in women] and reduced all-cause mortality [HRs (95% CIs) were 0.74 (0.72, 0.76) in men and 0.67 (0.65, 0.70) in women].ConclusionsIn both men and women, adherence to the ACS guidelines was associated with reductions in all-cancer incidence and the incidence of cancer at specific sites, as well as with reductions in cancer mortality and total mortality. These data suggest that, after accounting for cigarette smoking, adherence to a set of healthy behaviors may have considerable health benefits.

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Dataset Information

Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study.

Publications

Mortality and Cancer Incidence in Carriers of Balanced Robertsonian Translocations: A National Cohort Study.

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