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      Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies

      research-article
      1 , 2 , , 3 , 4 , 5 , 6 , 7 , 7 , 8 , 9 , 10 , 11 , 4 , 12 , 13 , 14 , 4 , 6 , 15 , 16 , 3 , 17 , 18 , 19 , 20 , 21 , 10 , 22 , 4 , 12 , 3 , 23 , 24 , 25 , 17 , 18 , 19 , 20 , 26 , 27 , 28 , 29 , 30 , 31 , 1 , 3 , 3 , 26 , 31 , 14 , 32 , 22 , 4 , 6 , 7 , 21 , 33 , 13 , 4 , 7
      European Journal of Epidemiology
      Springer Netherlands
      Breast neoplasms, Body height, Body weight, Weight change, Estrogen receptor, Cohort studies

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          Abstract

          Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose–response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6–7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively—and nonlinearly—associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18–20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m 2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18–20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

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          Meta-analysis in clinical trials.

          This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
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            Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults

            The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society
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              Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.

              Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.
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                Author and article information

                Contributors
                PA.vandenBrandt@maastrichtuniversity.nl
                Journal
                Eur J Epidemiol
                Eur J Epidemiol
                European Journal of Epidemiology
                Springer Netherlands (Dordrecht )
                0393-2990
                1573-7284
                30 October 2020
                30 October 2020
                2021
                : 36
                : 1
                : 37-55
                Affiliations
                [1 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Epidemiology, GROW – School for Oncology and Developmental Biology, , Maastricht University, ; PO Box 616, 6200 MD Maastricht, The Netherlands
                [2 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Epidemiology, Care and Public Health Institute (CAPHRI), , Maastricht University, ; PO Box 616, 6200 MD Maastricht, The Netherlands
                [3 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Division of Cancer Epidemiology and Genetics, National Cancer Institute, , National Institutes of Health, ; Bethesda, MD USA
                [4 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Epidemiology, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [5 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Biostatistics, , Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [6 ]GRID grid.38142.3c, ISNI 000000041936754X, Channing Division of Network Medicine, Department of Medicine, , Harvard Medical School, ; Boston, MA USA
                [7 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Nutrition, , Harvard T.H Chan School of Public Health, ; Boston, MA USA
                [8 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Medical Epidemiology and Biostatistics, , Karolinska Institutet, ; Stockholm, Sweden
                [9 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, Clinical Effectiveness Group, Institute of Health, , University of Oslo, ; Oslo, Norway
                [10 ]GRID grid.417893.0, ISNI 0000 0001 0807 2568, Epidemiology and Prevention Unit, Department of Research, , Fondazione Istituto Nazionale Tumori, ; 20133 Milan, Italy
                [11 ]GRID grid.410425.6, ISNI 0000 0004 0421 8357, Department of Population Sciences, Beckman Research Institute, , City of Hope, ; Duarte, CA USA
                [12 ]GRID grid.38142.3c, ISNI 000000041936754X, Division of Preventive Medicine, Brigham and Women’s Hospital, , Harvard Medical School, ; Boston, MA USA
                [13 ]GRID grid.137628.9, ISNI 0000 0004 1936 8753, Division of Epidemiology, Department of Population Health and Department of Environmental Medicine, , New York University School of Medicine, ; New York, USA
                [14 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Epidemiology, , Johns Hopkins Bloomberg School of Public Health, ; Baltimore, MD USA
                [15 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Epidemiology, , Columbia University Mailman School of Public Health, ; New York, NY USA
                [16 ]GRID grid.21729.3f, ISNI 0000000419368729, Herbert Irving Comprehensive Cancer Center, , Columbia University Irving Medical Center, ; New York, NY USA
                [17 ]GRID grid.3263.4, ISNI 0000 0001 1482 3639, Cancer Epidemiology Division, , Cancer Council Victoria, ; Melbourne, VIC Australia
                [18 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, , The University of Melbourne, ; Melbourne, VIC Australia
                [19 ]GRID grid.1002.3, ISNI 0000 0004 1936 7857, Precision Medicine, School of Clinical Sciences at Monash Health, , Monash University, ; Clayton, VIC Australia
                [20 ]GRID grid.270240.3, ISNI 0000 0001 2180 1622, Division of Public Health Sciences, , Fred Hutchinson Cancer Research Center, ; Seattle, WA USA
                [21 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, , Karolinska Institutet, ; Stockholm, Sweden
                [22 ]GRID grid.410445.0, ISNI 0000 0001 2188 0957, Cancer Epidemiology Program, , University of Hawaii Cancer Center, ; Honolulu, HI USA
                [23 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Family Medicine and Public Health School of Medicine, , University of California San Diego, ; La Jolla, CA USA
                [24 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Moores Cancer Center, , University of California San Diego, ; La Jolla, CA USA
                [25 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Dalla Lana School of Public Health, , University of Toronto, ; Toronto, ON Canada
                [26 ]GRID grid.422418.9, ISNI 0000 0004 0371 6485, Epidemiology Research Program, , American Cancer Society, ; Atlanta, GA USA
                [27 ]GRID grid.17635.36, ISNI 0000000419368657, Division of Hematology, Oncology and Transplantation, , University of Minnesota Medical School, ; Minneapolis, MN USA
                [28 ]GRID grid.17635.36, ISNI 0000000419368657, Division of Epidemiology and Community Health, School of Public Health, , University of Minnesota, ; Minneapolis, MN USA
                [29 ]GRID grid.253615.6, ISNI 0000 0004 1936 9510, Department of Exercise and Nutrition Sciences, , Milken Institute School of Public Health, George Washington University, ; Washington, DC USA
                [30 ]GRID grid.251993.5, ISNI 0000000121791997, Department of Epidemiology and Population Health, , Albert Einstein College of Medicine, ; Bronx, USA
                [31 ]GRID grid.272242.3, ISNI 0000 0001 2168 5385, Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, , National Cancer Center, ; Tokyo, Japan
                [32 ]GRID grid.17703.32, ISNI 0000000405980095, International Agency for Research on Cancer, World Health Organization, ; Lyon, France
                [33 ]GRID grid.8993.b, ISNI 0000 0004 1936 9457, Department of Surgical Sciences, , Uppsala University, ; Uppsala, Sweden
                Author information
                http://orcid.org/0000-0001-8781-8099
                Article
                688
                10.1007/s10654-020-00688-3
                7847460
                33128203
                241f5bbb-9bcf-45e7-afbf-41b16d2ffd66
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 August 2020
                : 26 September 2020
                Funding
                Funded by: Maastricht University Medical Center (UMC+)
                Categories
                Meta-Analysis
                Custom metadata
                © Springer Nature B.V. 2021

                Public health
                breast neoplasms,body height,body weight,weight change,estrogen receptor,cohort studies
                Public health
                breast neoplasms, body height, body weight, weight change, estrogen receptor, cohort studies

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