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The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal\/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.<\/jats:p>","DOI":"10.1002\/1878-0261.12772","type":"journal-article","created":{"date-parts":[[2020,8,2]],"date-time":"2020-08-02T16:19:08Z","timestamp":1596385148000},"page":"790-800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":572,"title":["Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4783-1966","authenticated-orcid":false,"given":"Christine M.","family":"Friedenreich","sequence":"first","affiliation":[{"name":"Department of Cancer Epidemiology and Prevention Research CancerControl Alberta Alberta Health Services Calgary AB Canada"},{"name":"Department of Oncology Cumming School of Medicine University of Calgary Calgary AB Canada"},{"name":"Department of Community Health Sciences Cumming School of Medicine University of Calgary Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-731X","authenticated-orcid":false,"given":"Charlotte","family":"Ryder\u2010Burbidge","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology and Prevention Research CancerControl Alberta Alberta Health Services Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-5812","authenticated-orcid":false,"given":"Jessica","family":"McNeil","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology and Prevention Research CancerControl Alberta Alberta Health Services Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32284"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.489"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2019.04.007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-6405.12471"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30383-X"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30357-7"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32129-3"},{"key":"e_1_2_11_9_1","volume-title":"2018 Physical Activity Guidelines Advisory Committee Scientific Report","author":"2018 Physical Activity Guidelines Advisory Committee","year":"2018"},{"key":"e_1_2_11_10_1","unstructured":"World Cancer Research Fund\/American Institute for Cancer Research(2018)Continuous Update Project Expert Report 2018. 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