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- Chen, Hongjie, et al.
(författare)
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Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
- 2021
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Ingår i: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
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- Dimou, Niki, et al.
(författare)
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Cigarette Smoking and Endometrial Cancer Risk : observational and Mendelian Randomization Analyses
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:9, s. 1839-1848
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.RESULTS: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.CONCLUSIONS: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. IMPACT: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
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- John, M. T., et al.
(författare)
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Recommendations for use and scoring of oral health impact profile versions
- 2022
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Ingår i: Journal of Evidence-Based Dental Practice. - Philadelphia, PA, United States : Elsevier. - 1532-3382 .- 1532-3390. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: OHIP's original seven-domain structure does not fit empirical data, but a psychometrically sound and clinically more plausible structure with the four OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact has emerged. Consequently, use and scoring of available OHIP versions need to be revisited. Aim: We assessed how well the overall construct OHRQoL and its four dimensions were measured with several OHIP versions (20, 19, 14, and 5 items) to derive recommendations which instruments should be used and how to score them. Methods: Data came from the “Dimensions of OHRQoL Project” and used the project's learning sample (5,173 prosthodontic patients and general population subjects with 49-item OHIP data). We computed correlations among OHIP versions’ summary scores. Correlations between OHRQoL dimensions, on one hand, and OHIP versions’ domain scores or OHIP-5′s items, on the other hand, were also computed. OHIP use and scoring recommendations were derived for psychometrically solid but also practical OHRQoL assessment. Results: Summary scores of 5-, 14-, 19- and 49-item versions correlated highly (r = 0.91–0.98), suggesting similar OHRQoL construct measurement across versions. The OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact were best measured by the OHIP domain scores for Physical Disability, Physical Pain, Psychological Discomfort, and Handicap, respectively. Conclusion: Recommendations were derived which OHIP should be preferably used and how OHIP versions should be scored to capture the overall construct and the dimensions of OHRQoL. Psychometrically solid and practical OHRQoL assessment in all settings across all oral health conditions can be achieved with the 5-item OHIP.
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- Brasky, Theodore M., et al.
(författare)
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Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium : An individual-participant meta-analysis
- 2023
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Ingår i: Gynecologic Oncology. - : Elsevier. - 0090-8258 .- 1095-6859. ; 169, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Background. Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial can-cer risk; particularly among certain subgroups characterized by body mass and tumor pathology.Materials and methods. Data from 12 prospective cohort studies participating in the Epidemiology of Endome-trial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid in-takes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study -specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.Results. Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were as-sociated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not dif-fer by cancer grade.Conclusion. Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly over-weight/obese women.(c) 2022 Elsevier Inc. All rights reserved.
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- John, Mike T., et al.
(författare)
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Mapping Oral Disease Impact with a Common Metric (MOM)—Project summary and recommendations
- 2021
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 48:3, s. 305-307
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Tidskriftsartikel (refereegranskat)abstract
- Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact—the dimensions of oral health-related quality of life—capture dental patients’ oral health problems worldwide and regardless of whether the patient currently suffers from oral diseases or intends to prevent them in the future. Using scores for these dimensions, the project Mapping Oral Disease Impact with a Common Metric (MOM) aims to provide four-dimensional oral health impact information across oral diseases and settings. In this article, project authors summarize MOM’s findings and provide recommendations about how to improve standardized oral health impact assessment. Project MOM’s systematic reviews identified four-dimensional impact information for 189 adult and 22 pediatric patient populations that were contained in 170 publications. A typical functional, pain-related, aesthetical, and psychosocial impact (on a 0-8 impact metric based on two items with a response format 0 = never, 1 = hardly ever, 2 = occasionally, 3 = fairly often, 4 = very often) was about 2 to 3 units. Project MOM provides five recommendations to improve standardized oral health impact assessment for all oral diseases in all settings.
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