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Träfflista för sökning "WFRF:(Friedenreich Christine M.) "

Sökning: WFRF:(Friedenreich Christine M.)

  • Resultat 1-10 av 14
  • [1]2Nästa
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1.
  • O’Mara, Tracy A., et al. (författare)
  • Identification of nine new susceptibility loci for endometrial cancer.
  • 2018
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
2.
  • Machiela, Mitchell J., et al. (författare)
  • Characterization of Large Structural Genetic Mosaicism in Human Autosomes
  • 2015
  • Ingår i: American Journal of Human Genetics. - 0002-9297. ; 96:3, s. 487-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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3.
  • Machiela, Mitchell J, et al. (författare)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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5.
  • Friedenreich, Christine, et al. (författare)
  • Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition
  • 2007
  • Ingår i: Cancer Causes and Control. - Springer. - 1573-7225. ; 18:4, s. 399-413
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups. Methods Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling. Results Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI >= 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of >= 88 cm vs. < 80 cm was 1.76, 95% CI = 1.42-2.19. Adult weight gain of >= 20 kg compared with stable weight (+/- 3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. Conclusion Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.
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6.
  • Friedenreich, Christine, et al. (författare)
  • Physical activity and risk of endometrial cancer: The European prospective investigation into cancer and nutrition
  • 2007
  • Ingår i: International Journal of Cancer. - John Wiley & Sons. - 0020-7136. ; 121:2, s. 347-355
  • Tidskriftsartikel (refereegranskat)abstract
    • The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was,undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI = 0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI = 0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI = 0.23-0.99) and 0.78 (95% CI = 0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities.
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7.
  • Pischon, Tobias, et al. (författare)
  • Body size and risk of colon and rectal cancer in the European prospective investigation into cancer and nutrition (EPIC)
  • 2006
  • Ingår i: Journal of the National Cancer Institute. - Oxford University Press. - 1460-2105. ; 98:13, s. 920-931
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Body weight and body mass index (BMI) are positively related to risk of colon cancer in men, whereas weak or no associations exist in women. This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy (HRT) in women. Methods: We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospective Investigation Into Cancer and Nutrition. All statistical tests were two-sided. Results: During 6.1 years of follow-up, we identified 984 and 586 patients with colon and rectal cancer, respectively. Body weight and BMI were statistically significantly associated with colon cancer risk in men (highest versus lowest quintile of BMI, relative risk [RR] = 1.55, 95% confidence interval [CI] = 1.12 to 2.15; P-trend =.006) but not in women. In contrast, comparisons of the highest to the lowest quintile showed that several anthropometric measures, including waist circumference (men, RR = 1.39,95% CI = 1.01 to 1.93; P-trend = .001; women, RR = 1.48, 95% CI = 1.08 to 2.03; P-trend =.008), waist-to-hip ratio (WHR; men, RR = 1.51, 95% CI = 1.06 to 2.15; P-trend =.006; women, RR = 1.52, 95% CI = 1.12 to 2.05; P-trend =.002), and height (men, RR = 1.40, 95% CI = 0.99 to 1.98; P-trend =.04; women, RR = 1.79, 95% CI = 1.30 to 2.46; P-trend <.001) were related to colon cancer risk in both sexes. The estimated absolute risk of developing colon cancer within 5 years was 203 and 131 cases per 100 000 men and 129 and 86 cases per 100000 women in the highest and lowest quintiles of WHR, respectively. Upon further stratification, no association of waist circumference and WHR with risk of colon cancer was observed among postmenopausal women who used HRT. None of the anthropometric measures was statistically significantly related to rectal cancer. Conclusions: Waist circumference and WHR, indicators of abdominal obesity, were strongly associated with colon cancer risk in men and women in this population. The association of abdominal obesity with colon cancer risk may vary depending on HRT use in postmenopausal women; however, these findings require confirmation in future studies.
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9.
  • Cust, Anne E., et al. (författare)
  • Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2007
  • Ingår i: Endocrine-Related Cancer. - Society for Endocrinology. - 1479-6821. ; 14:3, s. 755-767
  • Tidskriftsartikel (refereegranskat)abstract
    • To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
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