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- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Tan, Kristin H. X., et al.
(författare)
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Diabetes mellitus prevalence is increasing in South Asians but is stable in Chinese living in Singapore and Mauritius
- 2017
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Ingår i: Journal of Diabetes. - : John Wiley & Sons. - 1753-0393 .- 1753-0407. ; 9:9, s. 855-864
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asia is experiencing a type 2 diabetes epidemic but prevalence differs by ethnicity and level of socio-economic development. Singapore and Mauritius have implemented comprehensive campaigns to address this public health problem. We compared diabetes and obesity prevalence trends among Chinese and South Asians living in Singapore and Mauritius to determine the contribution of ethnicity and economic development to diabetes.METHODS: Age-specific data from serial national population-based surveys in Singapore and Mauritius between 1987 and 2010 were used to estimate age-standardised diabetes and obesity prevalence. Modified Breslow-Cox Proportional hazard models were used to obtain rate ratios for diabetes risk factors.RESULTS: In Singapore, the age-standardised prevalence of diabetes remained stable for Chinese (men 14% in 1992 and 13% in 2010; women 12% in 1992 and 10% in 2010); however, increases were observed for South Asians (men 20% in 1992 and 26% in 2010; women 18% in 1992 and 20% in 2010). There were similar patterns in Mauritius. In both countries, obesity prevalence trends were stable for Chinese women, but increased for Chinese men and South Asians. Associations between obesity and diabetes were stronger in Chinese than South Asians irrespective of country.CONCLUSIONS: Despite different socio-economic settings in Singapore and Mauritius, we observed rising diabetes prevalence among South Asians but stable prevalence in Chinese in both countries. This provides further evidence that ethnicity contributes to the development of diabetes, and that there should be an increased emphasis on future prevention strategies targeting South Asian populations in these countries.
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