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1.
  • Neugut, A., et al. (författare)
  • Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies
  • 2012
  • Ingår i: The Lancet. Oncology. - 1474-5488. ; 13:11, s. 1141-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons). Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. Funding Cancer Research UK.
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2.
  • Beral, V., et al. (författare)
  • Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
  • 2012
  • Ingår i: The Lancet Oncology. - Elsevier. - 1474-5488. ; 13:9, s. 946-956
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
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3.
  • Beral, V., et al. (författare)
  • Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
  • 2012
  • Ingår i: PLoS Medicine. - Public Library of Science. - 1549-1676. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
4.
  • Zhou, Bin, et al. (författare)
  • Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants
  • 2017
  • Ingår i: Lancet (London, England). - 1474-547X. ; 389:10064, s. 37-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7-128·3) in men and 122·3 mm Hg (121·0-123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9-79·5) for men and 76·7 mm Hg (75·9-77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4-27·1) in men and 20·1% (17·8-22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.Wellcome Trust.
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6.
  • Gapstur, S. M., et al. (författare)
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies
  • 2015
  • Ingår i: The Lancet. - Elsevier Limited. - 1474-547X. ; 385:9980, s. 1835-1842
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1.43, 95% CI 1.31-1.56; p<0.0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p<0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p<0.0001) and endometrioid (1.42, 1.20-1.67; p<0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
7.
  • Mavaddat, Nasim, et al. (författare)
  • Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes
  • 2019
  • Ingår i: American journal of human genetics. - 1537-6605. ; 104:1, s. 21-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs. © 2018 The Authors
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9.
  • Buckland, G, et al. (författare)
  • Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
  • 2014
  • Ingår i: International Journal of Cancer. - John Wiley & Sons. - 0020-7136. ; 134:10, s. 2504-2511
  • Tidskriftsartikel (refereegranskat)abstract
    • There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
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10.
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