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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 5. |
- Shi, Haonan, et al.
(författare)
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Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities : a cross-sectional study with interrupted time series analysis
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia.Methods: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019.Results: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding & GE; 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) & GE; 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0. 87-0.97; p = 0.0019), duration of breastfeeding & GE; 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001).Conclusions: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.
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