1304 results found
Wang A, Shen J, Rodriguez AA, et al., 2023, Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants., Nat Genet
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
Christakoudi S, Tsilidis K, Evangelou E, et al., 2023, Interactions of platelets with obesity in relation to lung cancer risk in the UK Biobank cohort, Respiratory Research, Vol: 24, ISSN: 1465-9921
Background:Platelet count (PLT) is associated positively with lung cancer risk but has a more complex association with body mass index (BMI), positive only in women (mainly never smokers) and inverse in men (mainly ever smokers), raising the question whether platelets interact with obesity in relation to lung cancer risk. Prospective associations of platelet size (an index of platelet maturity and activity) with lung cancer risk are unclear.Methods:We examined the associations of PLT, mean platelet volume (MPV), and platelet distribution width (PDW) (each individually, per one standard deviation increase) with lung cancer risk in UK Biobank men and women using multivariable Cox proportional hazards models adjusted for BMI and covariates. We calculated Relative Excess Risk from Interaction (RERI) with obese (BMI ≥30 kg/m2), dichotomising platelet parameters at ≥median (sex-specific), and multiplicative interactions with BMI (continuous scale). We examined heterogeneity according to smoking status (never, former, current smoker) and antiaggregant/anticoagulant use (no/yes).Results:During a mean follow-up of 10.4 years, 1620 lung cancers were ascertained in 192,355 men and 1495 lung cancers in 218,761 women. PLT was associated positively with lung cancer risk in men (hazard ratio HR=1.14; 95% confidence interval (CI): 1.09–1.20) and women (HR=1.09; 95%CI: 1.03–1.15) but interacted inversely with BMI only in men (RERI=-0.53; 95%CI: -0.80 to -0.26 for high-PLT-obese; HR=0.92; 95%CI=0.88–0.96 for PLTBMI). Only in men, MPV was associated inversely with lung cancer risk (HR=0.95; 95%CI: 0.90–0.99) and interacted positively with BMI (RERI=0.27; 95%CI=0.09–0.45 for high-MPV-obese; HR=1.08; 95%CI=1.04–1.13 for MPVBMI), while PDW was associated positively (HR=1.05; 95%CI: 1.00–1.10), with no evidence for interactions. The associations with PLT were consistent by smoking status, but MPV was associated inversely only in current sm
Berndt SI, Vijai J, Benavente Y, et al., 2023, Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes., Leukemia, Vol: 37
Guller ZE, Harewood RN, Weiderpass E, et al., 2023, Diet and lifestyle in relation to small intestinal cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC), CANCER CAUSES & CONTROL, Vol: 34, Pages: 927-937, ISSN: 0957-5243
King SD, Veliginti S, Brouwers MCGJ, et al., 2023, Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 32, ISSN: 1055-9965
Christakoudi S, Tsilidis K, Evangelou E, et al., 2023, Associations of obesity and body shape with erythrocyte and reticulocyte parameters in the UK Biobank cohort, BMC Endocrine Disorders, Vol: 23, Pages: 1-12, ISSN: 1472-6823
Background: Obesity is associated with type 2 diabetes mellitus and chronic low-grade inflammation. Although chronic inflammatory conditions and diabetes are associated with anaemia, less is known about associations of obesity and body shape, independent of each other, with erythrocyte and reticulocyte parameters.Methods: We investigated the associations of body mass index (BMI) and the allometric body shape index (ABSI) and hip index (HI), which are uncorrelated with BMI, with erythrocyte and reticulocyte parameters (all continuous, on a standard deviation (SD) scale) in UK Biobank participants without known metabolic, endocrine, or major inflammatory conditions (glycated haemoglobin HbA1c<48 mmol/mol, C-reactive protein CRP<10 mg/L). We examined erythrocyte count, total reticulocyte count and percent, immature reticulocyte count and fraction (IRF), haemoglobin, haematocrit, mean corpuscular haemoglobin mass (MCH) and concentration (MCHC), mean corpuscular and reticulocyte volumes (MCV, MPV), and red cell distribution width (RDW) in multivariable linear regression models. We additionally defined body shape phenotypes with dichotomised ABSI (≥73 women; ≥80 men) and HI (≥64 women; ≥49 men), including “pear” (small-ABSI-large-HI) and “apple” (large-ABSI-small-HI), and examined these in groups according to BMI (18.5-25 normal weight; 25-30 overweight; 30-45 kg/m2 obese). Results: In 105,853 women and 100,854 men, BMI and ABSI were associated positively with haemoglobin, haematocrit, and erythrocyte count, and more strongly with total reticulocyte count and percent, immature reticulocyte count and IRF. HI was associated inversely with all, but least with IRF. Associations were comparable in women and men. In groups according to obesity and body shape, erythrocyte count was ~0.6 SD higher for obese-“apple” compared to normal-weight-“pear” phenotype (SD=0.31*1012/L women, SD=0.34*1012/L men), total reticulo
Yarmolinsky J, Bouras E, Constantinescu A, et al., 2023, Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis, DIABETOLOGIA, Vol: 66, Pages: 1481-1500, ISSN: 0012-186X
Riboli E, Beland FA, Lachenmeier DW, et al., 2023, Carcinogenicity of aspartame, methyleugenol, and isoeugenol, LANCET ONCOLOGY, Vol: 24, Pages: 848-850, ISSN: 1470-2045
Zhao Y, Walker DI, Lill CM, et al., 2023, Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort, Journal of Neuroinflammation, Vol: 20, ISSN: 1742-2094
INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals.
Yew YW, Mina T, Ng HK, et al., 2023, Investigating causal relationships between obesity and skin barrier function in a multi-ethnic Asian general population cohort, International Journal of Obesity, Vol: 47, Pages: 963-969, ISSN: 0307-0565
BACKGROUND: Skin diseases impact significantly on the quality of life and psychology of patients. Obesity has been observed as a risk factor for skin diseases. Skin epidermal barrier dysfunctions are typical manifestations across several dermatological disturbances. OBJECTIVES: We aim to establish the association between obesity and skin physiology measurements and investigate whether obesity may play a possible causal role on skin barrier dysfunction. METHODS: We investigated the relationship of obesity with skin physiology measurements, namely transepidermal water loss (TEWL), skin surface moisture and skin pH in an Asian population cohort (n = 9990). To assess for a possible causal association between body mass index (BMI) and skin physiology measurements, we performed Mendelian Randomization (MR), along with subsequent additional analyses to assess the potential causal impact of known socioeconomic and comorbidities of obesity on TEWL. RESULTS: Every 1 kg/m2 increase in BMI was associated with a 0.221% (95%CI: 0.144-0.298) increase in TEWL (P = 2.82E-08), a 0.336% (95%CI: 0.148-0.524) decrease in skin moisture (P = 4.66E-04) and a 0.184% (95%CI: 0.144-0.224) decrease in pH (P = 1.36E-19), adjusting for age, gender, and ethnicity. Relationships for both TEWL and pH with BMI remained strong (Beta 0.354; 95%CI: 0.189-0.520 and Beta -0.170; 95%CI: -0.253 to -0.087, respectively) even after adjusting for known confounders, with MR experiments further supporting BMI's possible causal relationship with TEWL. Based on additional MR performed, none of the socioeconomic and comorbidities of obesity investigated are likely to have possible causal relationships with TEWL. CONCLUSION: We establish strong association of BMI with TEWL and skin pH, with MR results suggestive of a possible causal relationship of obesity with TEWL. It emphasizes the potential impact of obesity on skin barrier function and therefore op
Sanikini H, Biessy C, Rinaldi S, et al., 2023, Circulating hormones and risk of gastric cancer by subsite in three cohort studies, GASTRIC CANCER, ISSN: 1436-3291
Zheng B, Su B, Ahmadi-Abhari S, et al., 2023, Dementia risk in patients with type 2 diabetes: Comparing metformin with no pharmacological treatment, ALZHEIMERS & DEMENTIA, ISSN: 1552-5260
Koutros S, Kiemeney LA, Choudhury PP, et al., 2023, Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights, EUROPEAN UROLOGY, Vol: 84, Pages: 127-137, ISSN: 0302-2838
Clasen JL, Mabunda R, Heath AK, et al., 2023, Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition, Cancer Medicine, Vol: 12, Pages: 15588-15600, ISSN: 2045-7634
BackgroundRenal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & MethodsWe investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.ResultsDuring 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.ConclusionOur results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
Christakoudi S, Tsilidis KK, Dossus L, et al., 2023, A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort, BMC Cancer, Vol: 23, Pages: 1-12, ISSN: 1471-2407
Background: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). Methods: We evaluated body shape with the allometric “a body shape index” (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR=0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR=0.971; 0.942-1.000; n=5268 cases) and breast cancers diagnosed at age≥55 years (HR=0.976; 0.951-1.002; n=7043) and clear inverse associations for ER+PR- subtypes (HR=0.894; 0.822-0.971; n=726) and ER-PR- subtypes (HR=0.906; 0.835-0.983 n=759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR=1.074; 1.049-1.098), for post-menopausal women (HR=1.117; 1.085-1.150), for cancers diagnosed at age≥55 years (HR=1.104; 1.076-1.132), and for ER+PR+ subtypes (HR=1.122; 1.080-1.165; n=3101), but not for PR- subtypes. Conclusions: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger num
Middleton LT, Riboli E, 2023, Dietary Cholesterol and Dementia Risk, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, ISSN: 2274-5807
Heath AK, Tong TYN, Riboli E, 2023, Promotion of healthy nutrition for cardiovascular disease prevention – a multimodal approach is needed, European Journal of Preventive Cardiology, Vol: 30, Pages: 694-695, ISSN: 2047-4873
Aglago EK, Cross AJ, Riboli E, et al., 2023, Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study, British Journal of Cancer, Vol: 128, Pages: 1529-1540, ISSN: 0007-0920
BackgroundIron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.MethodsWe examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.ResultsOf 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).ConclusionsOur findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
Mina T, Yew YW, Ng HK, et al., 2023, Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study., The Lancet Regional Health. Western Pacific, Vol: 33, Pages: 1-11, ISSN: 2666-6065
BACKGROUND: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study. METHODS: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30-84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ' g ' was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ' g ' using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ' g ', using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition. FINDINGS: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ' g ' at P < 0.05. In multivariable analyses, reduced ' g ' was consistently associated with increased visceral fat mass index and lower HDL cholesterol (P < 0.001), but not with blood pressure, triglycerides, or glycemic indices. The reduction in ' g ' associated with 1SD higher visceral fat, or 1SD lower HDL cholesterol, was equivalent to a 0.7 and 0.9-year increase in chronological age respectively (P < 0.001). Inverse vari
Sobiecki JGD, Imamura F, Davis CR, et al., 2023, A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study, PLOS MEDICINE, Vol: 20, ISSN: 1549-1277
Ezzati M, Mishra A, Zhou B, et al., 2023, Diminishing benefits of urban living for children and adolescents’ growth and development, Nature, Vol: 615, Pages: 874-883, ISSN: 0028-0836
Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
Bonet C, Crous-Bou M, Tsilidis KK, et al., 2023, The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study, EUROPEAN JOURNAL OF EPIDEMIOLOGY, ISSN: 0393-2990
Christakoudi S, Tsilidis KK, Evangelou E, et al., 2023, Sex differences in the associations of body size and body shape with platelets in the UK Biobank cohort, Biology of Sex Differences, Vol: 14, Pages: 1-14, ISSN: 2042-6410
Background: Obesity is accompanied with low-grade inflammation and leucocytosis and increases the risk of venous thromboembolism. Associations with platelet count, however, are unclear because several studies have reported positive associations only in women. Associations with body shape are also unclear, because waist and hip circumferences reflect overall body size, as well as body shape, and are correlated strongly positively with body mass index (BMI).Methods: We evaluated body shape with the allometric body shape index (ABSI) and hip index (HI), which reflect waist and hip size among individuals with the same weight and height and are uncorrelated with BMI. We examined the associations of BMI, ABSI, and HI with platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) in multivariable linear regression models for 125,435 UK Biobank women and 114,760 men. We compared men with women, post-menopausal with pre-menopausal women, and older (≥52 years) with younger (<52 years) men.Results: BMI was associated positively with platelet count in women, more strongly in pre-menopausal than in post-menopausal, and weakly positively in younger men but strongly inversely in older men. Associations of BMI with platelet count were shifted towards the inverse direction for daily alcohol consumption and current smoking, resulting in weaker positive associations in women and stronger inverse associations in men, compared to alcohol≤3 times/month and never smoking. BMI was associated inversely with MPV and PDW in pre-menopausal women but positively in post-menopausal women and in men. ABSI was associated positively with platelet count, similarly in women and men, while HI was associated weakly inversely only in women. ABSI was associated inversely and HI positively with MPV but not with PDW and only in women. Platelet count was correlated inversely with platelet size and positively with leucocyte counts, most strongly with neutrophils. Conclusions:
Yammine SG, Huybrechts I, Biessy C, et al., 2023, Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition., BMC Cancer, Vol: 23, Pages: 1-12, ISSN: 1471-2407
BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Tsilidis KK, Cariolou M, Becerra-Tomas N, et al., 2023, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, Vol: 152, Pages: 635-644, ISSN: 0020-7136
Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
Chan DSM, Vieira R, Abar L, et al., 2023, Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 572-599, ISSN: 0020-7136
Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.
Cariolou M, Abar L, Aune D, et al., 2023, Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 600-615, ISSN: 0020-7136
It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded ‘limited-suggestive’ likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.
Becerra-Tomas N, Balducci K, Abar L, et al., 2023, Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 616-634, ISSN: 0020-7136
Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.
Wong E, Bertin N, Hebrard M, et al., 2023, The Singapore National Precision Medicine Strategy, NATURE GENETICS, Vol: 55, Pages: 178-+, ISSN: 1061-4036
Karavasiloglou N, Hughes DJ, Murphy N, et al., 2023, Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts, The American Journal of Clinical Nutrition, Vol: 117, Pages: 33-45, ISSN: 0002-9165
BACKGROUND: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. OBJECTIVES: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. METHODS: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. RESULTS: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. CONCLUSIONS: In UK-BB, higher serum ionized calcium
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