Shenying Fang

IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

BACKGROUND: Few studies have examined the outcomes for Hispanic men with prostate carcinoma and incorporated socioeconomic factors in association with race/ethnicity in affecting survival, adjusting for factors on cancer stage, grade, comorbidity, and treatment. METHODS: We studied a population-based cohort of 61,228 men diagnosed with local or regional stage prostate carcinoma at age 65 years or older between 1992 and 1999 in the 11 SEER (Surveillance, Epidemiology, and End Results) areas, identified from the SEER-Medicare linked data with up to 11 years of followup. RESULTS: Low socioeconomic status was significantly associated with decreasing survival in all men with prostate carcinoma. Those living in the community with the lowest quartile of socioeconomic status were 31% more likely to die than those living in the highest quartile (hazard ratio [HR] of all-cause mortality: 1.31; 95% confidence interval [CI]: 1.25-1.36) after adjustment for patient age, comorbidity, Gleason score, and treatment. The HR remained almost unchanged after controlling for race/ethnicity (HR: 1.32; 95% CI: 1.26-1.38). Compared with Caucasians, the risk of mortality in African American men was marginally significantly higher (HR: 1.06; 95% CI: 1.01-1.11) after controlling for education, and no longer significant after adjusting for poverty, income, or composite socioeconomic variable; the HR was lower for Hispanic men (HR: 0.80; 95% CI: 0.72-0.89) after adjustment for education and other socioeconomic variables. CONCLUSION: Racial disparity in survival among men with local or regional prostate carcinoma was largely explained by socioeconomic status and other factors. Lower socioeconomic status appeared to be one of the major barriers to achieving comparable outcomes for men with prostate carcinoma.