Abstract
Ovarian cancer is the most fatal gynecologic cancer and is an important source of cancer-related mortality, particularly in developed countries. Despite substantial research examining adiposity (primarily adult body mass index [BMI]), the overall evidence suggests only a weak positive association between adiposity and risk of ovarian cancer, with stronger associations observed for population-based case–control studies compared to prospective studies. Ovarian cancer is not one disease and emerging data suggest that higher BMI may only be associated with risk of certain histologic subtypes, including low-grade serous and invasive mucinous tumors. Interestingly, some larger studies and meta-analyses have reported a stronger relationship with premenopausal ovarian cancers, which are more likely to be of these subtypes. Relatively few studies have conducted detailed examinations of other adiposity-related factors such as measures of abdominal adiposity, early-life body size and weight change. While the underlying mechanisms that may relate adiposity to risk are unclear, increased inflammatory biomarkers have been associated with risk and hormonal factors, including androgen levels, may be important for the development of mucinous tumors. Future research should leverage the large sample sizes of consortia to evaluate associations by key tumor characteristics as well as consider patterns of weight change over the life course with both ovarian cancer risk and survival.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev 4(8):579–591. doi:10.1038/nrc1408
Renehan AG, Zwahlen M, Egger M (2015) Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer 15(8):484–498. doi:10.1038/nrc3967
The U.S. National Cancer Institute Obesity and Cancer Risk. http://www.cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet. Accessed 30 Nov 2015
American Cancer Society Does body weight affect cancer risk? http://www.cancer.org/cancer/cancercauses/dietandphysicalactivity/bodyweightandcancerrisk/body-weight-and-cancer-risk-effects. Accessed 30 Nov 2015
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. doi:10.3322/caac.21262
Yang HP, Anderson WF, Rosenberg PS, Trabert B, Gierach GL, Wentzensen N, Cronin KA, Sherman ME (2013) Ovarian cancer incidence trends in relation to changing patterns of menopausal hormone therapy use in the United States. J Clin Oncol (official journal of the American Society of Clinical Oncology) 31(17):2146–2151. doi:10.1200/jco.2012.45.5758
Flegal KM, Carroll MD, Kit BK, Ogden CL (2012) Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA 307(5):491–497. doi:10.1001/jama.2012.39
Jarboe EA, Folkins AK, Drapkin R, Ince TA, Agoston ES, Crum CP (2008) Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology 53(2):127–138. doi:10.1111/j.1365-2559.2007.02938.x
Rosen ED, Spiegelman BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444(7121):847–853. doi:10.1038/nature05483
Trayhurn P (2005) Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184(4):285–293. doi:10.1111/j.1365-201X.2005.01468.x
McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van Horn L, Wang CY (2006) Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity 14(9):1662–1677. doi:10.1038/oby.2006.191
Lukanova A, Lundin E, Zeleniuch-Jacquotte A, Muti P, Mure A, Rinaldi S, Dossus L, Micheli A, Arslan A, Lenner P, Shore RE, Krogh V, Koenig KL, Riboli E, Berrino F, Hallmans G, Stattin P, Toniolo P, Kaaks R (2004) Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Euro J Endocrinol/Eur Fed Endocr Soc 150(2):161–171
Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90(23):1774–1786
Lukanova A, Kaaks R (2005) Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomark Prev (A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology) 14(1):98–107
Cunat S, Hoffmann P, Pujol P (2004) Estrogens and epithelial ovarian cancer. Gynecol Oncol 94(1):25–32. doi:10.1016/j.ygyno.2004.03.026
Helzlsouer KJ, Alberg AJ, Gordon GB, Longcope C, Bush TL, Hoffman SC, Comstock GW (1995) Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA 274(24):1926–1930
Schock H, Surcel HM, Zeleniuch-Jacquotte A, Grankvist K, Lakso HA, Fortner RT, Kaaks R, Pukkala E, Lehtinen M, Toniolo P, Lundin E (2014) Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer. Endocr Relat Cancer 21(6):831–844. doi:10.1530/erc-14-0282
Lukanova A, Lundin E, Akhmedkhanov A, Micheli A, Rinaldi S, Zeleniuch-Jacquotte A, Lenner P, Muti P, Biessy C, Krogh V, Berrino F, Hallmans G, Riboli E, Kaaks R, Toniolo P (2003) Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer 104(5):636–642. doi:10.1002/ijc.10990
Hecht JL, Kotsopoulos J, Hankinson SE, Tworoger SS (2009) Relationship between epidemiologic risk factors and hormone receptor expression in ovarian cancer: results from the Nurses’ Health Study. Cancer Epidemiol Biomark Prev (A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology) 18(5):1624–1630. doi:10.1158/1055-9965.epi-08-1214
Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, Schatzkin A, Schairer C (2002) Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 288(3):334–341
Beral V, Bull D, Green J, Reeves G (2007) Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 369(9574):1703–1710. doi:10.1016/s0140-6736(07)60534-0
Beral V, Gaitskell K, Hermon C, Moser K, Reeves G, Peto R (2015) Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 385(9980):1835–1842. doi:10.1016/s0140-6736(14)61687-1
Ness RB, Grisso JA, Klapper J, Schlesselman JJ, Silberzweig S, Vergona R, Morgan M, Wheeler JE (2000) Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid hormones and reproductions. Am J Epidemiol 152(3):233–241
Gross TP, Schlesselman JJ (1994) The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer. Obstet Gynecol 83(3):419–424
Barry JA, Azizia MM, Hardiman PJ (2014) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 20(5):748–758. doi:10.1093/humupd/dmu012
Rinaldi S, Dossus L, Lukanova A, Peeters PH, Allen NE, Key T, Bingham S, Khaw KT, Trichopoulos D, Trichopoulou A, Oikonomou E, Pera G, Larranaga N, Martinez-Garcia C, Ardanaz E, Quiros JR, Tormo MJ, Tjonneland A, Olsen A, Overvad K, Chang-Claude J, Linseisen J, Schulz M, Boeing H, van Gils CH, Bueno-de-Mesquita BH, Pala V, Palli D, Panico S, Tumino R, Vineis P, Clavel-Chapelon F, Mesrine S, Boutron-Ruault MC, Lundin E, Agren A, Berglund G, Manjer J, Kumle M, Lund E, Slimani N, Saracci R, Riboli E, Kaaks R (2007) Endogenous androgens and risk of epithelial ovarian cancer: results from the european prospective investigation into cancer and nutrition (EPIC). Cancer Epidemiol Biomarkers Prev 16(1):23–29. doi:10.1158/1055-9965.EPI-06-0755
Tworoger SS, Lee IM, Buring JE, Hankinson SE (2008) Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol 167(2):211–218. doi:10.1093/aje/kwm278
Olsen CM, Green AC, Nagle CM, Jordan SJ, Whiteman DC, Bain CJ, Webb PM (2008) Epithelial ovarian cancer: testing the ‘androgens hypothesis’. Endocr Relat Cancer 15(4):1061–1068. doi:10.1677/erc-08-0075
Ose J, Fortner RT, Rinaldi S, Schock H, Overvad K, Tjonneland A, Hansen L, Dossus L, Fournier A, Baglietto L, Romieu I, Kuhn E, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Masala G, Sieri S, Tumino R, Sacerdote C, Mattiello A, Ramon Quiros J, Obon-Santacana M, Larranaga N, Chirlaque MD, Sanchez MJ, Barricarte A, Peeters PH, Bueno-de-Mesquita HB, Onland-Moret NC, Brandstedt J, Lundin E, Idahl A, Weiderpass E, Gram IT, Lund E, Kaw KT, Travis RC, Merritt MA, Gunther MJ, Riboli E, Kaaks R (2015) Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer J Int Cancer 136(2):399–410. doi:10.1002/ijc.29000
Resnicoff M, Ambrose D, Coppola D, Rubin R (1993) Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines. Lab Invest (A Journal of Technical Methods and Pathology) 69(6):756–760
Ji QS, Mulvihill MJ, Rosenfeld-Franklin M, Cooke A, Feng L, Mak G, O’Connor M, Yao Y, Pirritt C, Buck E, Eyzaguirre A, Arnold LD, Gibson NW, Pachter JA (2007) A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor dependent tumor growth in vivo. Mol Cancer Ther 6(8):2158–2167. doi:10.1158/1535-7163.mct-07-0070
Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, Zeleniuch-Jacquotte A, Berrino F, Hallmans G, Riboli E, Kaaks R (2002) Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer J Int Cancer 101(6):549–554. doi:10.1002/ijc.10613
Peeters PH, Lukanova A, Allen N, Berrino F, Key T, Dossus L, Rinaldi S, van Gils CH, Bueno-de-Mesquita HB, Boeing H, Schulz M, Chang-Claude J, Linseisen J, Panico S, Sacerdote C, Palli D, Tumino R, Trichopoulou A, Trichopolos D, Bamia C, Larranaga N, Ardanaz E, Pera G, Quiros JR, Martinez-Garcia C, Navarro C, Bingham SA, Khaw KT, Clavel F, Tjonneland A, Olsen A, Overvad K, Tetsche MS, Lund E, Lundin E, Berglund G, Riboli E, Kaaks R (2007) Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the european prospective investigation into cancer and nutrition (EPIC). Endocr Relat Cancer 14(1):81–90. doi:10.1677/erc.1.01264
Tworoger SS, Lee IM, Buring JE, Pollak MN, Hankinson SE (2007) Insulin-like growth factors and ovarian cancer risk: a nested case-control study in three cohorts. Cancer Epidemiol Biomark Prev (A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology) 16(8):1691–1695. doi:10.1158/1055-9965.epi-07-0319
Schock H, Fortner RT, Surcel HM, Grankvist K, Pukkala E, Lehtinen M, Lundin E (2015) Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: a nested case-control study. Int J Cancer J Int Cancer 137(2):439–447. doi:10.1002/ijc.29387
Ose J, Fortner RT, Schock H, Peeters PH, Onland-Moret NC, Bueno-de-Mesquita HB, Weiderpass E, Gram IT, Overvad K, Tjonneland A, Dossus L, Fournier A, Baglietto L, Trichopoulou A, Benetou V, Trichopoulos D, Boeing H, Masala G, Krogh V, Matiello A, Tumino R, Popovic M, Obon-Santacana M, Larranaga N, Ardanaz E, Sanchez MJ, Menendez V, Chirlaque MD, Travis RC, Khaw KT, Brandstedt J, Idahl A, Lundin E, Rinaldi S, Kuhn E, Romieu I, Gunter MJ, Merritt MA, Riboli E, Kaaks R (2015) Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort. Br J Cancer 112(1):162–166. doi:10.1038/bjc.2014.566
Dal Maso L, Augustin LS, Franceschi S, Talamini R, Polesel J, Kendall CW, Jenkins DJ, Vidgen E, La Vecchia C (2004) Association between components of the insulin-like growth factor system and epithelial ovarian cancer risk. Oncology 67(3–4):225–230. doi:10.1159/000081322
Wang Q, Bian CE, Peng H, He L, Zhao X (2015) Association of circulating insulin-like growth factor 1 and insulin-like growth factor binding protein 3 with the risk of ovarian cancer: a systematic review and meta-analysis. Mol Clin Oncol 3(3):623–628. doi:10.3892/mco.2015.516
Sayer RA, Lancaster JM, Pittman J, Gray J, Whitaker R, Marks JR, Berchuck A (2005) High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 96(2):355–361. doi:10.1016/j.ygyno.2004.10.012
Flyvbjerg A, Mogensen O, Mogensen B, Nielsen OS (1997) Elevated serum insulin-like growth factor-binding protein 2 (IGFBP-2) and decreased IGFBP-3 in epithelial ovarian cancer: correlation with cancer antigen 125 and tumor-associated trypsin inhibitor. J Clin Endocrinol Metab 82(7):2308–2313. doi:10.1210/jcem.82.7.4085
Karasik A, Menczer J, Pariente C, Kanety H (1994) Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endocrinol Metab 78(2):271–276. doi:10.1210/jcem.78.2.7508947
Baron-Hay S, Boyle F, Ferrier A, Scott C (2004) Elevated serum insulin-like growth factor binding protein-2 as a prognostic marker in patients with ovarian cancer. Clin Cancer Res (An Official journal of the American Association for Cancer Research) 10(5):1796–1806
Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132(6):2169–2180. doi:10.1053/j.gastro.2007.03.059
Fleming JS, Beaugie CR, Haviv I, Chenevix-Trench G, Tan OL (2006) Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol 247(1–2):4–21. doi:10.1016/j.mce.2005.09.014
Maccio A, Lai P, Santona MC, Pagliara L, Melis GB, Mantovani G (1998) High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein correlate with impairment of T cell response in patients with advanced epithelial ovarian cancer. Gynecol Oncol 69(3):248–252. doi:10.1006/gyno.1998.4974
Moradi MM, Carson LF, Weinberg B, Haney AF, Twiggs LB, Ramakrishnan S (1993) Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in patients with ovarian epithelial cancer. Cancer 72(8):2433–2440
Maccio A, Madeddu C (2012) Inflammation and ovarian cancer. Cytokine 58(2):133–147. doi:10.1016/j.cyto.2012.01.015
Rzymski P, Opala T, Wilczak M, Wozniak J, Sajdak S (2005) Serum tumor necrosis factor alpha receptors p55/p75 ratio and ovarian cancer detection. Int J Gynaecol Obstet 88(3):292–298. doi:10.1016/j.ijgo.2004.12.015
Lane D, Matte I, Rancourt C, Piche A (2011) Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer 11:210. doi:10.1186/1471-2407-11-210
Lo CW, Chen MW, Hsiao M, Wang S, Chen CA, Hsiao SM, Chang JS, Lai TC, Rose-John S, Kuo ML, Wei LH (2011) IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res 71(2):424–434. doi:10.1158/0008-5472.CAN-10-1496
Clendenen TV, Lundin E, Zeleniuch-Jacquotte A, Koenig KL, Berrino F, Lukanova A, Lokshin AE, Idahl A, Ohlson N, Hallmans G, Krogh V, Sieri S, Muti P, Marrangoni A, Nolen BM, Liu M, Shore RE, Arslan AA (2011) Circulating inflammation markers and risk of epithelial ovarian cancer. Cancer Epidemiol Biomark Prev 20(5):799–810. doi:10.1158/1055-9965.EPI-10-1180
Ose J, Schock H, Tjonneland A, Hansen L, Overvad K, Dossus L, Clavel-Chapelon F, Baglietto L, Boeing H, Trichopolou A, Benetou V, Lagiou P, Masala G, Tagliabue G, Tumino R, Sacerdote C, Mattiello A, Bueno-de-Mesquita HB, Peeters PH, Onland-Moret NC, Weiderpass E, Gram IT, Sanchez S, Obon-Santacana M, Sanchez-Perez MJ, Larranaga N, Castano JM, Ardanaz E, Brandstedt J, Lundin E, Idahl A, Travis RC, Khaw KT, Rinaldi S, Romieu I, Merritt MA, Gunter MJ, Riboli E, Kaaks R, Fortner RT (2015) Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.EPI-14-1279-T
Poole EM, Lee IM, Ridker PM, Buring JE, Hankinson SE, Tworoger SS (2013) A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol 178(8):1256–1264. doi:10.1093/aje/kwt098
Trabert B, Pinto L, Hartge P, Kemp T, Black A, Sherman ME, Brinton LA, Pfeiffer RM, Shiels MS, Chaturvedi AK, Hildesheim A, Wentzensen N (2014) Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial. Gynecol Oncol 135(2):297–304. doi:10.1016/j.ygyno.2014.08.025
McSorley MA, Alberg AJ, Allen DS, Allen NE, Brinton LA, Dorgan JF, Pollak M, Tao Y, Helzlsouer KJ (2007) C-reactive protein concentrations and subsequent ovarian cancer risk. Obstet Gynecol 109(4):933–941. doi:10.1097/01.AOG.0000257126.68803.03
Toriola AT, Grankvist K, Agborsangaya CB, Lukanova A, Lehtinen M, Surcel HM (2011) Changes in pre-diagnostic serum C-reactive protein concentrations and ovarian cancer risk: a longitudinal study. Ann Oncol 22(8):1916–1921. doi:10.1093/annonc/mdq694
Lundin E, Dossus L, Clendenen T, Krogh V, Grankvist K, Wulff M, Sieri S, Arslan AA, Lenner P, Berrino F, Hallmans G, Zeleniuch-Jacquotte A, Toniolo P, Lukanova A (2009) C-reactive protein and ovarian cancer: a prospective study nested in three cohorts (Sweden, USA, Italy). Cancer Causes Control 20(7):1151–1159. doi:10.1007/s10552-009-9330-2
Pyragius CE, Fuller M, Ricciardelli C, Oehler MK (2013) Aberrant lipid metabolism: an emerging diagnostic and therapeutic target in ovarian cancer. Int J Mol Sci 14(4):7742–7756. doi:10.3390/ijms14047742
Tania M, Khan MA, Song Y (2010) Association of lipid metabolism with ovarian cancer. Curr Oncol 17(5):6–11
Hiatt RA, Fireman BH (1986) Serum cholesterol and the incidence of cancer in a large cohort. J Chronic Dis 39(11):861–870
Helzlsouer KJ, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW (1996) Prospective study of serum micronutrients and ovarian cancer. J Natl Cancer Inst 88(1):32–37
Melvin JC, Seth D, Holmberg L, Garmo H, Hammar N, Jungner I, Walldius G, Lambe M, Wigertz A, Van Hemelrijck M (2012) Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study. Cancer Epidemiol Biomark Prev 21(8):1381–1384. doi:10.1158/1055-9965.EPI-12-0188
Li AJ, Elmore RG, Chen IY, Karlan BY (2010) Serum low-density lipoprotein levels correlate with survival in advanced stage epithelial ovarian cancers. Gynecol Oncol 116(1):78–81. doi:10.1016/j.ygyno.2009.09.027
Ades A, Carvalho JP, Graziani SR, Amancio RF, Souen JS, Pinotti JA, Maranhao RC (2001) Uptake of a cholesterol-rich emulsion by neoplastic ovarian tissues. Gynecol Oncol 82(1):84–87. doi:10.1006/gyno.2001.6203
Scoles DR, Xu X, Wang H, Tran H, Taylor-Harding B, Li A, Karlan BY (2010) Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein. Gynecol Oncol 116(1):109–116. doi:10.1016/j.ygyno.2009.09.034
Lavie O, Pinchev M, Rennert HS, Segev Y, Rennert G (2013) The effect of statins on risk and survival of gynecological malignancies. Gynecol Oncol 130(3):615–619. doi:10.1016/j.ygyno.2013.05.025
Boudreau DM, Yu O, Johnson J (2010) Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf 9(4):603–621. doi:10.1517/14740331003662620
Olsen CM, Green AC, Whiteman DC, Sadeghi S, Kolahdooz F, Webb PM (2007) Obesity and the risk of epithelial ovarian cancer: a systematic review and meta-analysis. European journal of cancer (Oxford, England: 1990) 43(4):690–709. doi:10.1016/j.ejca.2006.11.010
Aune D, Navarro Rosenblatt DA, Chan DS, Abar L, Vingeliene S, Vieira AR, Greenwood DC, Norat T (2015) Anthropometric factors and ovarian cancer risk: a systematic review and nonlinear dose-response meta-analysis of prospective studies. Int J Cancer J Int Cancer 136(8):1888–1898. doi:10.1002/ijc.29207
Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies (2012). PLoS medicine 9(4):e1001200. doi:10.1371/journal.pmed.1001200
Purdie DM, Bain CJ, Webb PM, Whiteman DC, Pirozzo S, Green AC (2001) Body size and ovarian cancer: case-control study and systematic review (Australia). Cancer Causes Control (CCC) 12(9):855–863
Schouten LJ, Rivera C, Hunter DJ, Spiegelman D, Adami HO, Arslan A, Beeson WL, van den Brandt PA, Buring JE, Folsom AR, Fraser GE, Freudenheim JL, Goldbohm RA, Hankinson SE, Lacey JV Jr, Leitzmann M, Lukanova A, Marshall JR, Miller AB, Patel AV, Rodriguez C, Rohan TE, Ross JA, Wolk A, Zhang SM, Smith-Warner SA (2008) Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomark Prev (A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology) 17(4):902–912. doi:10.1158/1055-9965.epi-07-2524
Kurian AW, Balise RR, McGuire V, Whittemore AS (2005) Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol Oncol 96(2):520–530. doi:10.1016/j.ygyno.2004.10.037
Engeland A, Tretli S, Bjorge T (2003) Height, body mass index, and ovarian cancer: a follow-up of 1.1 million Norwegian women. J Natl Cancer Inst 95(16):1244–1248
Olsen CM, Nagle CM, Whiteman DC, Ness R, Pearce CL, Pike MC, Rossing MA, Terry KL, Wu AH, Risch HA, Yu H, Doherty JA, Chang-Claude J, Hein R, Nickels S, Wang-Gohrke S, Goodman MT, Carney ME, Matsuno RK, Lurie G, Moysich K, Kjaer SK, Jensen A, Hogdall E, Goode EL, Fridley BL, Vierkant RA, Larson MC, Schildkraut J, Hoyo C, Moorman P, Weber RP, Cramer DW, Vitonis AF, Bandera EV, Olson SH, Rodriguez-Rodriguez L, King M, Brinton LA, Yang H, Garcia-Closas M, Lissowska J, Anton-Culver H, Ziogas A, Gayther SA, Ramus SJ, Menon U, Gentry-Maharaj A, Webb PM (2013) Obesity and risk of ovarian cancer subtypes: evidence from the ovarian cancer association consortium. Endocr Relat Cancer 20(2):251–262. doi:10.1530/erc-12-0395
Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D (2007) Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. BMJ (Clinical Research ed) 335(7630):1134. doi:10.1136/bmj.39367.495995.AE
Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L (2014) Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet 384(9945):755–765. doi:10.1016/s0140-6736(14)60892-8
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X
Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2005) Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria. Br J Cancer 93(9):1062–1067. doi:10.1038/sj.bjc.6602819
Stunkard AJ, Albaum JM (1981) The accuracy of self-reported weights. Am J Clin Nutr 34(8):1593–1599
Palta M, Prineas RJ, Berman R, Hannan P (1982) Comparison of self-reported and measured height and weight. Am J Epidemiol 115(2):223–230
Niedhammer I, Bugel I, Bonenfant S, Goldberg M, Leclerc A (2000) Validity of self-reported weight and height in the French GAZEL cohort. Int J Obes Relat Metab Disord (Journal of the International Association for the Study of Obesity) 24(9):1111–1118
Shih Ie M, Kurman RJ (2004) Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol 164(5):1511–1518
Kurman RJ, Shih Ie M (2008) Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol (Official Journal of the International Society of Gynecological Pathologists) 27(2):151–160. doi:10.1097/PGP.0b013e318161e4f5
Merritt MA, De Pari M, Vitonis AF, Titus LJ, Cramer DW, Terry KL (2013) Reproductive characteristics in relation to ovarian cancer risk by histologic pathways. Hum Reprod (Oxford, England) 28(5):1406–1417. doi:10.1093/humrep/des466
Risch HA, Marrett LD, Jain M, Howe GR (1996) Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case-control study. Am J Epidemiol 144(4):363–372
Kobel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, Leung S, Bowen NJ, Ionescu DN, Rajput A, Prentice LM, Miller D, Santos J, Swenerton K, Gilks CB, Huntsman D (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5(12):e232. doi:10.1371/journal.pmed.0050232
Kaaks R, Lukanova A, Kurzer MS (2002) Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomark Prev 11(12):1531–1543
Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40(9):1213–1223. doi:10.1016/j.humpath.2009.04.017
Gilks CB (2004) Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data. Int J Gynecol Pathol (Official Journal of the International Society of Gynecological Pathologists) 23(3):200–205
Olsen CM, Nagle CM, Whiteman DC, Purdie DM, Green AC, Webb PM (2008) Body size and risk of epithelial ovarian and related cancers: a population-based case-control study. Int J Cancer J Int Cancer 123(2):450–456. doi:10.1002/ijc.23509
Lahmann PH, Cust AE, Friedenreich CM, Schulz M, Lukanova A, Kaaks R, Lundin E, Tjonneland A, Halkjaer J, Severinsen MT, Overvad K, Fournier A, Chabbert-Buffet N, Clavel-Chapelon F, Dossus L, Pischon T, Boeing H, Trichopoulou A, Lagiou P, Naska A, Palli D, Grioni S, Mattiello A, Tumino R, Sacerdote C, Redondo ML, Jakszyn P, Sanchez MJ, Tormo MJ, Ardanaz E, Arriola L, Manjer J, Jirstrom K, Bueno-de-Mesquita HB, May AM, Peeters PH, Onland-Moret NC, Bingham S, Khaw KT, Allen NE, Spencer E, Rinaldi S, Slimani N, Chajes V, Michaud D, Norat T, Riboli E (2010) Anthropometric measures and epithelial ovarian cancer risk in the European prospective investigation into cancer and nutrition. Int J Cancer J Int Cancer 126(10):2404–2415. doi:10.1002/ijc.24952
Kotsopoulos J, Baer HJ, Tworoger SS (2010) Anthropometric measures and risk of epithelial ovarian cancer: results from the nurses’ health study. Obesity 18(8):1625–1631. doi:10.1038/oby.2009.461
Ma X, Beeghly-Fadiel A, Shu XO, Li H, Yang G, Gao YT, Zheng W (2013) Anthropometric measures and epithelial ovarian cancer risk among Chinese women: results from the Shanghai Women’s Health Study. Br J Cancer 109(3):751–755. doi:10.1038/bjc.2013.384
Rimm EB, Stampfer MJ, Colditz GA, Chute CG, Litin LB, Willett WC (1990) Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1(6):466–473
Baer HJ, Colditz GA, Rosner B, Michels KB, Rich-Edwards JW, Hunter DJ, Willett WC (2005) Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study. Breast Cancer Res 7(3):R314–R325
Baer HJ, Tworoger SS, Hankinson SE, Willett WC (2010) Body fatness at young ages and risk of breast cancer throughout life. Am J Epidemiol 171(11):1183–1194. doi:10.1093/aje/kwq045
Dougan MM, Hankinson SE, Vivo ID, Tworoger SS, Glynn RJ, Michels KB (2015) Prospective study of body size throughout the life-course and the incidence of endometrial cancer among premenopausal and postmenopausal women. Int J Cancer J Int Cancer 137(3):625–637. doi:10.1002/ijc.29427
Kuper H, Cramer DW, Titus-Ernstoff L (2002) Risk of ovarian cancer in the United States in relation to anthropometric measures: does the association depend on menopausal status? Cancer Causes Control (CCC) 13(5):455–463
Peterson NB, Trentham-Dietz A, Newcomb PA, Chen Z, Gebretsadik T, Hampton JM, Stampfer MJ, Willett WC, Egan KM (2006) Relation of anthropometric measurements to ovarian cancer risk in a population-based case-control study (United States). Cancer Causes Control (CCC) 17(4):459–467. doi:10.1007/s10552-005-0416-1
Baer HJ, Hankinson SE, Tworoger SS (2008) Body size in early life and risk of epithelial ovarian cancer: results from the Nurses’ Health Studies. Br J Cancer 99(11):1916–1922. doi:10.1038/sj.bjc.6604742
Spracklen CN, Wallace RB, Sealy-Jefferson S, Robinson JG, Freudenheim JL, Wellons MF, Saftlas AF, Snetselaar LG, Manson JE, Hou L, Qi L, Chlebowski RT, Ryckman KK (2014) Birth weight and subsequent risk of cancer. Cancer Epidemiol 38(5):538–543. doi:10.1016/j.canep.2014.07.004
Yang TO, Reeves GK, Green J, Beral V, Cairns BJ (2014) Birth weight and adult cancer incidence: large prospective study and meta-analysis. Ann Oncol (Official Journal of the European Society for Medical Oncology/ESMO) 25(9):1836–1843. doi:10.1093/annonc/mdu214
Keum N, Greenwood DC, Lee DH, Kim R, Aune D, Ju W, Hu FB, Giovannucci EL (2015) Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J Natl Cancer Inst 107(2). doi:10.1093/jnci/djv088
Canchola AJ, Chang ET, Bernstein L, Largent JA, Reynolds P, Deapen D, Henderson KD, Ursin G, Horn-Ross PL (2010) Body size and the risk of ovarian cancer by hormone therapy use in the California Teachers Study cohort. Cancer Causes Control (CCC) 21(12):2241–2248. doi:10.1007/s10552-010-9647-x
Schouten LJ, Goldbohm RA, van den Brandt PA (2003) Height, weight, weight change, and ovarian cancer risk in the Netherlands cohort study on diet and cancer. Am J Epidemiol 157(5):424–433
Fairfield KM, Willett WC, Rosner BA, Manson JE, Speizer FE, Hankinson SE (2002) Obesity, weight gain, and ovarian cancer. Obstet Gynecol 100(2):288–296
Jonsson F, Wolk A, Pedersen NL, Lichtenstein P, Terry P, Ahlbom A, Feychting M (2003) Obesity and hormone-dependent tumors: cohort and co-twin control studies based on the Swedish twin registry. Int J Cancer 106(4):594–599
Hoyo C, Berchuck A, Halabi S, Bentley RC, Moorman P, Calingaert B, Schildkraut JM (2005) Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women. Cancer Causes Control (CCC) 16(8):955–963. doi:10.1007/s10552-005-3205-y
Greer JB, Modugno F, Ness RB, Allen GO (2006) Anthropometry and the risk of epithelial ovarian cancer. Cancer 106(10):2247–2257. doi:10.1002/cncr.21830
Hunn J, Rodriguez GC (2012) Ovarian cancer: etiology, risk factors, and epidemiology. Clin Obstet Gynecol 55(1):3–23. doi:10.1097/GRF.0b013e31824b4611
Gao SK, Beresford SA, Frank LL, Schreiner PJ, Burke GL, Fitzpatrick AL (2008) Modifications to the Healthy Eating Index and its ability to predict obesity: the multi-ethnic study of atherosclerosis. Am J Clin Nutr 88(1):64–69
Fung TT, Pan A, Hou T, Chiuve SE, Tobias DK, Mozaffarian D, Willett WC, Hu FB (2015) Long-term change in diet quality is associated with body weight change in men and women. J Nutr 145(8):1850–1856. doi:10.3945/jn.114.208785
Mozaffarian D, Hao T, Rimm EB, Willett WC, Hu FB (2011) Changes in diet and lifestyle and long-term weight gain in women and men. N Engl J Med 364(25):2392–2404. doi:10.1056/NEJMoa1014296
Xie J, Poole EM, Terry KL, Fung TT, Rosner BA, Willett WC, Tworoger SS (2014) A prospective cohort study of dietary indices and incidence of epithelial ovarian cancer. J Ovarian Res 7:112. doi:10.1186/s13048-014-0112-4
Chandran U, Bandera EV, Williams-King MG, Paddock LE, Rodriguez-Rodriguez L, Lu SE, Faulkner S, Pulick K, Olson SH (2011) Healthy eating index and ovarian cancer risk. Cancer Causes Control (CCC) 22(4):563–571. doi:10.1007/s10552-011-9728-5
Chang ET, Lee VS, Canchola AJ, Dalvi TB, Clarke CA, Reynolds P, Purdie DM, Stram DO, West DW, Ziogas A, Bernstein L, Horn-Ross PL (2008) Dietary patterns and risk of ovarian cancer in the California Teachers Study cohort. Nutr Cancer 60(3):285–291. doi:10.1080/01635580701733091
Cannioto RA, Moysich KB (2015) Epithelial ovarian cancer and recreational physical activity: a review of the epidemiological literature and implications for exercise prescription. Gynecol Oncol 137(3):559–573. doi:10.1016/j.ygyno.2015.03.016
Bertone ER, Willett WC, Rosner BA, Hunter DJ, Fuchs CS, Speizer FE, Colditz GA, Hankinson SE (2001) Prospective study of recreational physical activity and ovarian cancer. J Natl Cancer Inst 93(12):942–948
Anderson JP, Ross JA, Folsom AR (2004) Anthropometric variables, physical activity, and incidence of ovarian cancer: the Iowa Women’s Health Study. Cancer 100(7):1515–1521. doi:10.1002/cncr.20146
Chionh F, Baglietto L, Krishnan K, English DR, MacInnis RJ, Gertig DM, Hopper JL, Giles GG (2010) Physical activity, body size and composition, and risk of ovarian cancer. Cancer Causes Control (CCC) 21(12):2183–2194. doi:10.1007/s10552-010-9638-y
Huang T, Eliassen AH, Hankinson SE, Okereke OI, Kubzansky LD, Wang M, Poole EM, Chavarro JE, Tworoger SS (2015) A prospective study of leisure-time physical activity and risk of incident epithelial ovarian cancer: Impact by menopausal status. Int J Cancer J Int Cancer. doi:10.1002/ijc.29834
Soler M, Chatenoud L, Negri E, Parazzini F, Franceschi S, la Vecchia C (1999) Hypertension and hormone-related neoplasms in women. Hypertension 34(2):320–325
Bjorge T, Lukanova A, Tretli S, Manjer J, Ulmer H, Stocks T, Selmer R, Nagel G, Almquist M, Concin H, Hallmans G, Jonsson H, Haggstrom C, Stattin P, Engeland A (2011) Metabolic risk factors and ovarian cancer in the metabolic syndrome and cancer project. Int J Epidemiol 40(6):1667–1677. doi:10.1093/ije/dyr130
Adler AI, Weiss NS, Kamb ML, Lyon JL (1996) Is diabetes mellitus a risk factor for ovarian cancer? A case-control study in Utah and Washington (United States). Cancer Causes Control (CCC) 7(4):475–478
Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S (2006) Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 166(17):1871–1877. doi:10.1001/archinte.166.17.1871
Gapstur SM, Patel AV, Diver WR, Hildebrand JS, Gaudet MM, Jacobs EJ, Campbell PT (2012) Type II diabetes mellitus and the incidence of epithelial ovarian cancer in the cancer prevention study-II nutrition cohort. Cancer Epidemiol Biomark Prev (A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology) 21(11):2000–2005. doi:10.1158/1055-9965.epi-12-0867
Swerdlow AJ, Laing SP, Qiao Z, Slater SD, Burden AC, Botha JL, Waugh NR, Morris AD, Gatling W, Gale EA, Patterson CC, Keen H (2005) Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 92(11):2070–2075. doi:10.1038/sj.bjc.6602611
Strasak AM, Pfeiffer RM, Brant LJ, Rapp K, Hilbe W, Oberaigner W, Lang S, Borena W, Concin H, Diem G, Ruttmann E, Glodny B, Pfeiffer KP, Ulmer H (2009) Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol (Official Journal of the European Society for Medical Oncology/ESMO) 20(6):1113–1120. doi:10.1093/annonc/mdn736
Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177(3):1053–1064. doi:10.2353/ajpath.2010.100105
Califano D, Pignata S, Losito NS, Ottaiano A, Greggi S, De Simone V, Cecere S, Aiello C, Esposito F, Fusco A, Chiappetta G (2014) High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer. J Cell Physiol 229(1):53–59. doi:10.1002/jcp.24416
Hess LM, Barakat R, Tian C, Ozols RF, Alberts DS (2007) Weight change during chemotherapy as a potential prognostic factor for stage III epithelial ovarian carcinoma: a gynecologic oncology group study. Gynecol Oncol 107(2):260–265. doi:10.1016/j.ygyno.2007.06.010
Suh DH, Kim HS, Chung HH, Kim JW, Park NH, Song YS, Kang SB (2012) Body mass index and survival in patients with epithelial ovarian cancer. J Obstet Gynaecol Res 38(1):70–76. doi:10.1111/j.1447-0756.2011.01628.x
Au-Yeung G, Webb PM, DeFazio A, Fereday S, Bressel M, Mileshkin L (2014) Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian ovarian cancer study (AOCS). Gynecol Oncol 133(1):16–22. doi:10.1016/j.ygyno.2014.01.030
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E (2011) Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 17(11):1498–1503. doi:10.1038/nm.2492
Kato S, Abarzua-Catalan L, Trigo C, Delpiano A, Sanhueza C, Garcia K, Ibanez C, Hormazabal K, Diaz D, Branes J, Castellon E, Bravo E, Owen G, Cuello MA (2015) Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women. Oncotarget 6(25):21100–21119
Ptak A, Kolaczkowska E, Gregoraszczuk EL (2013) Leptin stimulation of cell cycle and inhibition of apoptosis gene and protein expression in OVCAR-3 ovarian cancer cells. Endocrine 43(2):394–403. doi:10.1007/s12020-012-9788-7
Yang HS, Yoon C, Myung SK, Park SM (2011) Effect of obesity on survival of women with epithelial ovarian cancer: a systematic review and meta-analysis of observational studies. Int J Gynecol Cancer (Official Journal of the International Gynecological Cancer Society) 21(9):1525–1532. doi:10.1097/IGC.0b013e31822eb5f8
Protani MM, Nagle CM, Webb PM (2012) Obesity and ovarian cancer survival: a systematic review and meta-analysis. Cancer prevention research 5(7):901–910. doi:10.1158/1940-6207.capr-12-0048
Bae HS, Kim HJ, Hong JH, Lee JK, Lee NW, Song JY (2014) Obesity and epithelial ovarian cancer survival: a systematic review and meta-analysis. J Ovarian Res 7:41. doi:10.1186/1757-2215-7-41
Nagle CM, Dixon SC, Jensen A, Kjaer SK, Modugno F, deFazio A, Fereday S, Hung J, Johnatty SE, Fasching PA, Beckmann MW, Lambrechts D, Vergote I, Van Nieuwenhuysen E, Lambrechts S, Risch HA, Rossing MA, Doherty JA, Wicklund KG, Chang-Claude J, Goodman MT, Ness RB, Moysich K, Heitz F, du Bois A, Harter P, Schwaab I, Matsuo K, Hosono S, Goode EL, Vierkant RA, Larson MC, Fridley BL, Hogdall C, Schildkraut JM, Weber RP, Cramer DW, Terry KL, Bandera EV, Paddock L, Rodriguez-Rodriguez L, Wentzensen N, Yang HP, Brinton LA, Lissowska J, Hogdall E, Lundvall L, Whittemore A, McGuire V, Sieh W, Rothstein J, Sutphen R, Anton-Culver H, Ziogas A, Pearce CL, Wu AH, Webb PM (2015) Obesity and survival among women with ovarian cancer: results from the ovarian cancer association consortium. Br J Cancer 113(5):817–826. doi:10.1038/bjc.2015.245
Smits A, Lopes A, Das N, Bekkers R, Galaal K (2015) Quality of life in ovarian cancer survivors: the influence of obesity. Int J Gynecol Cancer (Official Journal of the International Gynecological Cancer Society) 25(4):616–621. doi:10.1097/igc.0000000000000388
Smits A, Smits E, Lopes A, Das N, Hughes G, Talaat A, Pollard A, Bouwman F, Massuger L, Bekkers R, Galaal K (2015) Body mass index, physical activity and quality of life of ovarian cancer survivors: time to get moving? Gynecol Oncol 139(1):148–154. doi:10.1016/j.ygyno.2015.08.005
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Tworoger, S.S., Huang, T. (2016). Obesity and Ovarian Cancer. In: Pischon, T., Nimptsch, K. (eds) Obesity and Cancer. Recent Results in Cancer Research, vol 208. Springer, Cham. https://doi.org/10.1007/978-3-319-42542-9_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-42542-9_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-42540-5
Online ISBN: 978-3-319-42542-9
eBook Packages: MedicineMedicine (R0)