| 1. |
- Campanella, Gianluca, et al.
(författare)
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Epigenome-wide association study of adiposity and future risk of obesity-related diseases
- 2018
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 42:12, s. 2022-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors.Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.
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| 2. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 3. |
- Luczynska, Anna, et al.
(författare)
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Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: American Journal of Clinical Nutrition. - Rockville Pike, Bethesda, MD, USA : Elsevier BV. - 1938-3207 .- 0002-9165. ; 98:3, s. 827-838
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relation between vitamin D status and lymphoma risk is inconclusive. Objective: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. Design: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. Results: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with >= 2y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Conclusions: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.
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| 4. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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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. |
- Michaud, Dominique S., et al.
(författare)
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Anthropometric Measures, Physical Activity, and Risk of Glioma and Meningioma in a Large Prospective Cohort Study
- 2011
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Ingår i: Cancer Prevention Research. - Philadelphia, PA : American Association for Cancer Research, Inc.. - 1940-6207 .- 1940-6215. ; 4:9, s. 1385-1392
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Tidskriftsartikel (refereegranskat)abstract
- Body fatness has been associated with increased risk of a number of hormone-dependent cancers. Recent studies suggest that body mass index (BMI) may be related to meningiomas, which are more common in women than men, and for which estrogens are believed to play a role. Using data from a large European propective cohort, 203 incident cases of meningioma and 340 cases of glioma were included in the analysis for measures of body fat, height, and physical activity among 380,775 participants. All analyses were conducted using Cox proportional hazards model and controlling for age, sex, country, and education. A 71% increase in risk of meningioma was observed among men and women in the top quartile of waist circumference (HR = 1.71, 95% CI = 1.08-2.73, P-trend = 0.01). A positive association was also observed for BMI and meningioma (HR = 1.48, 95% CI = 0.98-2.23, for BMI >= 30 compared with a BMI of 20-24.9, P-trend = 0.05). An association with height and meningioma was also suggestive (HR = 1.24, 95% 0.96-1.51, for each 10 cm increase). In contrast, no associations were observed for height and different measures of body fat and risk of glioma. Physical activity was not related to either type of brain tumors. Results from this study support an increase in risk of meningioma with higher body fatness among both men and women. No association was observed between anthropometric measures and risk of glioma. Cancer Prev Res; 4(9); 1385-92. (C) 2011 AACR.
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| 6. |
- Michaud, Dominique S, et al.
(författare)
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Coffee and tea intake and risk of brain tumors in the European prospective investigation into cancer and nutrition (EPIC) cohort study
- 2010
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Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 92:5, s. 1145-1150
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma.Objective: The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC).Design: Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors.Results: We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant.Conclusions: In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas.
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| 7. |
- Michaud, Dominique S., et al.
(författare)
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Reproductive Factors and Exogenous Hormone Use in Relation to Risk of Glioma and Meningioma in a Large European Cohort Study
- 2010
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 19:10, s. 2562-2569
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI). Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46). Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation. Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562-9. (C) 2010 AACR.
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| 8. |
- Rohrmann, Sabine, et al.
(författare)
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Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European prospective investigation into cancer and nutrition
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:10, s. 2174-2182
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin-like growth factor-1 (IGF-I) is important in normal brain development but in the adult brain, IGF-I overexpression may be a risk factor for tumor development. METHODS: We examined the association between circulating concentrations of IGF-I and IGFBP-3 in relation to risk of gliomas (74 low-grade, 206 high-grade gliomas), meningiomas (n = 174) and acoustic neuromas (n = 49) by using a case-control design nested in the European Prospective Investigation into Cancer and Nutrition. IGF-I and IGFBP-3 were measured by ELISAs.Conditional logistic regression was used to compute ORs and corresponding 95% CIs. RESULTS: The risk of low-grade gliomas was elevated with increased IGF-I (OR = 3.60, 95% CI: 1.11-11.7; top vs. bottom quartile) and decreased with elevated IGFBP-3 concentrations (OR = 0.28, 95% CI: 0.09-0.84) after mutual adjustment of these two factors; these results became nonsignificant after exclusion of the first year of follow-up. No association was observed for high-grade gliomas or meningiomas. Both high IGF-I and IGFBP-3 concentrations were associated with risk of acoustic neuromas (IGF-I: OR = 6.63, 95% CI: 2.27-19.4, top vs. bottom tertile; IGFBP-3: OR = 7.07, 95% CI: 2.32-21.6), even after excluding the first year of follow-up. CONCLUSION: High concentrations of IGF-I might be positively associated with risk of low-grade gliomas and acoustic neuromas, although we cannot exclude reverse causation, in particular for low-grade gliomas. Impact: Factors of the IGF axis might be involved in the etiology of some types of brain tumors. Cancer Epidemiol Biomarkers Prev; ©2011 AACR.
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| 9. |
- Rohrmann, Sabine, et al.
(författare)
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Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition
- 2011
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Ingår i: International Journal of Cancer. - Geneve : Wiley. - 0020-7136 .- 1097-0215. ; 128:3, s. 623-634
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Tidskriftsartikel (refereegranskat)abstract
- The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [ relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.
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| 10. |
- Roulland, Sandrine, et al.
(författare)
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t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma
- 2014
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Ingår i: Journal of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 32:13, s. 1347-1347
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. Participants and Methods Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. Results Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. Conclusion High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.
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