| 1. |
- 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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| 2. |
- Adel Fahmideh, Maral, et al.
(författare)
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A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06-1.49], p=0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.
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| 3. |
- Adel Fahmideh, Maral, et al.
(författare)
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Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
- 2016
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratifid analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected. This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.
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| 4. |
- Adel Fahmideh, Maral, et al.
(författare)
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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.
- 2018
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Ingår i: Clinical epidemiology. - 1179-1349. ; 10, s. 729-738
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Tidskriftsartikel (refereegranskat)abstract
- Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring.The study was a population-based nested case-control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536).Compared with offspring of fathers aged 25-29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35-39 years (odds ratio [OR]=1.43 [95% CI 1.16-1.74]) and ≥40 years (OR =1.74 [95% CI 1.38-2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01-1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age.The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers.
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| 5. |
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| 6. |
- Brooke, Hannah L, et al.
(författare)
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Adult children's socioeconomic resources and mothers' survival after a breast cancer diagnosis : a Swedish population-based cohort study.
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Socioeconomic inequalities in survival after breast cancer persist worldwide. We aim to determine whether adult offspring's socioeconomic resources contribute to inequalities in mothers' survival after breast cancer.METHODS: 14 231 women, aged 65-79 years, with a child aged ≥30 years and a first primary diagnosis of breast cancer in the National Cancer Register between 2001 and 2010 were followed until death, 10 years after diagnosis, or end of study (December 2015). Relative survival proportions and excess mortality within 10 years of diagnosis by strata of offspring's education level and disposable income were estimated using flexible parametric models accounting for measures of mothers' socioeconomic position and expected mortality in the general population.RESULTS: 4292 women died during 102 236 person-years of follow-up. Crude 10-year relative survival proportions for mothers of children with >14, 12-14 and <12 years of education were 0.89 (0.87 to 0.91), 0.87 (0.85 to 0.89) and 0.79 (0.76 to 0.81), respectively. Compared with mothers of children with >14 years of education, mothers of children with <12 or 12-14 years of education had substantially higher excess mortality (excess HR 1.69 (1.38 to 2.07) and 1.22 (1.00 to 1.48), respectively). Higher mortality did not differ between tertiles of offspring's disposable income.CONCLUSIONS: Adult offspring's education level may contribute to inequalities in mothers' survival after breast cancer. Clinicians should be aware of the educational context beyond the individual and women with less educated offsprings may require extra support. This should be considered in future research, policy frameworks and interventions aimed at reducing survival inequalities.
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| 7. |
- Brooke, Hannah L, et al.
(författare)
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Methodological choices affect cancer incidence rates : a cohort study.
- 2017
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Ingår i: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Incidence rates are fundamental to epidemiology, but their magnitude and interpretation depend on methodological choices. We aimed to examine the extent to which the definition of the study population affects cancer incidence rates.METHODS: All primary cancer diagnoses in Sweden between 1958 and 2010 were identified from the national Cancer Register. Age-standardized and age-specific incidence rates of 29 cancer subtypes between 2000 and 2010 were calculated using four definitions of the study population: persons resident in Sweden 1) based on general population statistics; 2) with no previous subtype-specific cancer diagnosis; 3) with no previous cancer diagnosis except non-melanoma skin cancer; and 4) with no previous cancer diagnosis of any type. We calculated absolute and relative differences between methods.RESULTS: Age-standardized incidence rates calculated using general population statistics ranged from 6% lower (prostate cancer, incidence rate difference: -13.5/100,000 person-years) to 8% higher (breast cancer in women, incidence rate difference: 10.5/100,000 person-years) than incidence rates based on individuals with no previous subtype-specific cancer diagnosis. Age-standardized incidence rates in persons with no previous cancer of any type were up to 10% lower (bladder cancer in women) than rates in those with no previous subtype-specific cancer diagnosis; however, absolute differences were <5/100,000 person-years for all cancer subtypes.CONCLUSIONS: For some cancer subtypes incidence rates vary depending on the definition of the study population. For these subtypes, standardized incidence ratios calculated using general population statistics could be misleading. Moreover, etiological arguments should be used to inform methodological choices during study design.
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| 8. |
- Brooke, Hannah L, et al.
(författare)
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Socioeconomic position and incidence of colorectal cancer in the Swedish population.
- 2016
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 40, s. 188-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The association between socioeconomic position and incidence of colorectal cancer is inconsistent and differs by global region. We aimed to clarify this association in the Swedish population.METHODS: We conducted a population-based open cohort study using data from Swedish national registers. We included all individuals, aged ≥30 years, residing in Sweden between 1993 and 2010. Socioeconomic position was indicated by (1) highest educational level (five groups), and (2) disposable income (quintiles). We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (95% CI) of colon and rectal cancer, and colon and rectal dysplasia.RESULTS: In total, 97,827,817 person-years were accumulated and 82,686 cases of colorectal cancer were diagnosed. Compared to men with 'higher secondary' education, the adjusted IRRs (95% CI) of rectal cancer in men with 'primary or less', 'lower secondary', 'lower university' or 'higher university' education were: 1.06 (1.00, 1.11), 1.05 (0.99, 1.10), 0.96 (0.89, 1.03), and 0.92 (0.86, 0.98), respectively. In women, the corresponding figures were: 1.04 (0.95, 1.14), 1.03 (0.94, 1.13), 0.92 (0.82, 1.02) and 0.92 (0.82, 1.02). Disposable income was not associated with rectal cancer incidence. Adjusted IRRs of colon cancer did not differ between levels of education or disposable income overall or for specific colon sub-sites. Neither education nor disposable income was consistently associated with incidence of colon or rectal dysplasia.CONCLUSIONS: Prevention strategies for colon cancer should be applicable to individuals regardless of their socioeconomic position. However, factors conferred by education, e.g., health awareness, may be important for approaches aiming to reduce inequalities in incidence of rectal cancer. Further evaluation of cancer prevention and health promotion strategies among less educated groups is warranted.
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| 9. |
- Brooke, Hannah Louise, et al.
(författare)
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The Swedish cause of death register
- 2017
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Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 32:9, s. 765-773
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.
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| 10. |
- Deleskog, Anna, et al.
(författare)
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Maternal diabetes and incidence of childhood cancer : a nationwide cohort study and exploratory genetic analysis
- 2017
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Ingår i: Clinical Epidemiology. - 1179-1349. ; 9, s. 633-642
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma.Methods: All children born in Sweden between 1973 and 2014 (n= 4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015. Data on maternal diabetes, childhood cancer, and covariates were obtained from nationwide health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusted for potential confounders/mediators. Additionally, we performed an exploratory analysis using results from published genome-wide association studies and functional annotation.Results: Maternal diabetes was associated with lower risk of CBT (adjusted IRR [95% CI]: 0.56 [0.35-0.91]) and higher risk of leukemia (adjusted IRR: 1.47 [1.13-1.92] for all leukemia combined and 1.64 [1.23-2.18] for ALL). These associations were similar for both maternal type 1 diabetes and gestational diabetes. Associations of five previously identified genetic loci were compatible with a causal effect of diabetes traits on neuroblastoma and common Hodgkin's lymphoma.Conclusion: Children whose mother had diabetes had lower risk of CBT and higher risk of leukemia, compared with children whose mother did not have diabetes. Our results are compatible with a role of prenatal and perinatal glycemic environment in childhood cancer etiology.
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