Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe

Heinz Freisling, Melina Arnold, Isabelle Soerjomataram, Mark George O'Doherty, José Manuel Ordóñez-Mena, Christina Bamia, Ellen Kampman, Michael Leitzmann, Isabelle Romieu, Frank Kee, Konstantinos Tsilidis, Anne Tjønneland, Antonia Trichopoulou, Paolo Boffetta, Vassiliki Benetou, H B As Bueno-de-Mesquita, José María Huerta, Hermann Brenner, Tom Wilsgaard, Mazda Jenab, Heinz Freisling, Melina Arnold, Isabelle Soerjomataram, Mark George O'Doherty, José Manuel Ordóñez-Mena, Christina Bamia, Ellen Kampman, Michael Leitzmann, Isabelle Romieu, Frank Kee, Konstantinos Tsilidis, Anne Tjønneland, Antonia Trichopoulou, Paolo Boffetta, Vassiliki Benetou, H B As Bueno-de-Mesquita, José María Huerta, Hermann Brenner, Tom Wilsgaard, Mazda Jenab

Abstract

Background: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.

Methods: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models.

Results: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users.

Conclusions: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of participant inclusion.
Figure 2
Figure 2
Random-effects meta-analysis of the association of different obesity indicators per 1 standard deviation (s.d.) increment with ‘obesity-related cancers’a.aFirst primary cancers of the breast (postmenopausal), colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney. Adjustments were made for sex, age at entry, daily smoking (never, former, current, missing), average alcohol consumption (g per day), education (primary or less, more than primary but less than college, college or university, missing), vigorous physical activity (yes, no, missing), recruitment year, and height. BMI=body mass index; DK=Denmark; GR=Greece; HC=hip circumference; NL=The Netherlands; SP=Spain; WC=waist circumference; WHR=waist-to-hip ratio.
Figure 3
Figure 3
Random-effects meta-analysis of the association of different obesity indicators per 1 standard deviation (s.d.) increment with colorectal cancer. Adjustments were made for sex, age at entry, daily smoking (never, former, current, missing), average alcohol consumption (g per day), education (primary or less, more than primary but less than college, college or university, missing), vigorous physical activity (yes, no, missing), recruitment year, and height. BMI=body mass index; DK=Denmark; GR=Greece; HC=hip circumference; NL=The Netherlands; SP=Spain; WC=waist circumference; WHR=waist-to-hip ratio.
Figure 4
Figure 4
Random-effects meta-analysis of the association of different obesity indicators per 1 standard deviation (s.d.) increment with postmenopausal breast cancer. Adjustments were made for age at entry, daily smoking (never, former, current, missing), average alcohol consumption (g per day), education (primary or less, more than primary but less than college, college or university, missing), vigorous physical activity (yes, no, missing), recruitment year, and height. BMI=body mass index; DK=Denmark; GR=Greece; HC=hip circumference; NL=The Netherlands; SP=Spain; WC=waist circumference; WHR=waist-to-hip ratio.
Figure 5
Figure 5
Random-effects meta-analysis of the association of different obesity indicators per 1 standard deviation (s.d.) increment with ‘other obesity-related cancers’a.aFirst primary cancers of the lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney. Adjustments were made for sex, age at entry, daily smoking (never, former, current, missing), average alcohol consumption (g per day), education (primary or less, more than primary but less than college, college or university, missing), vigorous physical activity (yes, no, missing), recruitment year, and height. BMI=body mass index; DK=Denmark; GR=Greece; HC=hip circumference; NL=the Netherlands; SP=Spain; WC=waist circumference; WHR=waist-to-hip ratio.

References

    1. Anderson AS, Key TJ, Norat T, Scoccianti C, Cecchini M, Berrino F, Boutron-Ruault MC, Espina C, Leitzmann M, Powers H, Wiseman M, Romieu I (2015) European code against cancer 4th edition: Obesity, body fatness and cancer. Cancer Epidemiol 39(Suppl 1): S34–S45.
    1. Arnold M, Freisling H, Stolzenberg-Solomon R, Kee F, O’Doherty MG, Ordóñez-Mena JM, Wilsgaard T, May AM, Bueno-de-Mesquita HB, Tjønneland A, Orfanos P, Trichopoulou A, Boffetta P, Bray F, Jenab M, Soerjomataram I CHANCES consortium (2016. a) Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States. Eur J Epidemiol 31: 893–904.
    1. Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A, Soerjomataram I (2016. b) Obesity and cancer: An update of the global impact. Cancer Epidemiol 41: 8–15.
    1. Aune D, Greenwood DC, Chan DSM, Vieira R, Vieira AR, Navarro Rosenblatt DA, Cade JE, Burley VJ, Norat T (2012) Body mass index, abdominal fatness and pancreatic cancer risk: A systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol 23: 843–852.
    1. Aune D, Navarro Rosenblatt Da, Chan DSM, Abar L, Vingeliene S, Vieira AR, Greenwood DC, Norat T (2015. a) Anthropometric factors and ovarian cancer risk: A systematic review and nonlinear dose-response meta-analysis of prospective studies. Int J Cancer 136: 1888–1898.
    1. Aune D, Navarro Rosenblatt DA, Chan DSM, Vingeliene S, Abar L, Vieira AR, Greenwood DC, Bandera EV, Norat T (2015. b) Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol 26: 1635–1648.
    1. 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: 755–765.
    1. Boffetta P, Bobak M, Borsch-Supan A, Brenner H, Eriksson S, Grodstein F, Jansen E, Jenab M, Juerges H, Kampman E, Kee F, Kuulasmaa K, Park Y, Tjonneland A, van Duijn C, Wilsgaard T, Wolk A, Trichopoulos D, Bamia C, Trichopoulou A (2014) The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project–design, population and data harmonization of a large-scale, international study. Eur J Epidemiol 29: 929–936.
    1. Cameron AJ, Magliano DJ, Söderberg S (2013) A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality. Obes Rev 14: 86–94.
    1. Fibrinogen Studies Collaboration (2009) Measures to assess the prognostic ability of the stratified Cox proportional hazardsmodel. Stat Med 28: 389–411.
    1. Dalamaga M, Diakopoulos KN, Mantzoros CS (2012) The Role of Adiponectin in Cancer: A Review of Current Evidence. Endocr Rev 33: 547–594.
    1. Folsom AR, Kushi LH, Anderson KE, Mink PJ, Olson JE, Hong C-P, Sellers TA, Lazovich D, Prineas RJ (2000) Associations of General and Abdominal Obesity With Multiple Health Outcomes in Older Women. Arch Intern Med 160: 2117–2128.
    1. Gaudet MM, Carter BD, Patel AV, Teras LR, Jacobs EJ, Gapstur SM (2014) Waist circumference, body mass index, and postmenopausal breast cancer incidence in the Cancer Prevention Study-II Nutrition Cohort. Cancer Causes Control 25: 737–745.
    1. Gaudet MM, Kitahara CM, Newton CC, Bernstein L, Reynolds P, Weiderpass E, Kreimer AR, Yang G, Adami H-O, Alavanja MC, Beane Freeman LE, Boeing H, Buring J, Chaturvedi A, Chen Y, D’Aloisio AA, Freedman M, Gao Y-T, Gaziano JM, Giles GG, Hakansson N, Huang W-Y, Lee I-M, Linet MS, MacInnis RJ, Park Y, Prizment A, Purdue MP, Riboli E, Robien K, Sandler DP, Schairer C, Sesso HD, Ou Shu X, White E, Wolk A, Xiang Y-B, Zelenuich-Jacquotte A, Zheng W, Patel AV, Hartge P, Berrington de Gonzalez A, Gapstur SM (2015) Anthropometry and head and neck cancer:a pooled analysis of cohort data. Int J Epidemiol 44: 673–681.
    1. Harris RJ, Bradburn MJ, Deeks JJ, Altman DG, Harbord RM, Sterne JaC (2008) Metan: Fixed- and random-effects meta-analysis. Stata J 8: 3–28.
    1. Heitmann BL, Lissner L (2011) Hip Hip Hurrah! Hip size inversely related to heart disease and total mortality. Obes Rev 12: 478–481.
    1. Higgins JPT, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539–1558.
    1. Hu FB (2008) Obesity epidemiology. Oxford University Press: Oxford New York.
    1. Keimling M, Renehan AG, Behrens G, Fischer B, Hollenbeck AR, Cross AJ, Leitzmann MF (2013) Comparison of associations of body mass index, abdominal adiposity, and risk of colorectal cancer in a Large Prospective Cohort Study. Cancer Epidemiol Biomarkers Prev 22: 1383–1394.
    1. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K (2016) Body fatness and cancer–viewpoint of the IARC Working Group. N Engl J Med 375: 794–798.
    1. Lee CH, Woo YC, Wang Y, Yeung CY, Xu A, Lam KSL (2015) Obesity, adipokines and cancer: An update. Clin Endocrinol (Oxf) 83: 147–156.
    1. Moore LL, Bradlee ML, Singer MR, Splansky GL, Proctor MH, Ellison RC, Kreger BE (2004) BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int J Obes Relat Metab Disord 28: 559–567.
    1. National Heart, Lung and Blood Institute (1998) Clinical Guidelineson the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Report No, 98-4083.
    1. NCD Risk Factor Collaboration (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387: 1377–1396.
    1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NME, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang J-C, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DFJ, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green Ma, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SEAH, Kengne AP, Khader YS, Khang Y-H, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KMV, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJC, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon S-J, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJL, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384: 766–781.
    1. O’Doherty MG, Freedman ND, Hollenbeck AR, Schatzkin A, Abnet CC (2012) A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study. Gut 61: 1261–1268.
    1. Orsini N, Greenland S (2011) A procedure to tabulate and plot results after flexible modeling of a quantitative covariate. Stata J 11: 1–29.
    1. Park J, Morley TS, Kim M, Clegg DJ, Scherer PE (2014) Obesity and cancer—mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol 10: 455–465.
    1. Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjønneland A, Halkjaer J, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Guernec G, Bergmann MM, Linseisen J, Becker N, Trichopoulou A, Trichopoulos D, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PHM, Bueno-de-Mesquita HB, Boshuizen HC, Van Guelpen B, Palmqvist R, Berglund G, Gonzalez CA, Dorronsoro M, Barricarte A, Navarro C, Martinez C, Quirós JR, Roddam A, Allen N, Bingham S, Khaw KT, Ferrari P, Kaaks R, Slimani N, Riboli E (2006) Body size and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 98: 920–931.
    1. Renehan AG, Flood A, Adams KF, Olden M, Hollenbeck AR, Cross AJ, Leitzmann MF (2012) Body mass index at different adult ages, weight change, and colorectal cancer risk in the National Institutes of Health-AARP cohort. Am J Epidemiol 176: 1130–1140.
    1. 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: 569–578.
    1. Renehan AG, Zwahlen M, Egger M (2015) Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer 15: 484–498.
    1. Roswall N, Freisling H, Bueno-de-Mesquita HBA, Ros M, Christensen J, Overvad K, Boutron-Ruault M-C, Severi G, Fagherazzi G, Chang-Claude J, Kaaks R, Steffen A, Boeing H, Argüelles M, Agudo A, Sánchez M-J, Chirlaque M-D, Barricarte Gurrea A, Amiano P, Wareham N, Khaw K-T, Bradbury KE, Trichopoulou A, Papatesta H-M, Trichopoulos D, Palli D, Pala V, Tumino R, Sacerdote C, Mattiello A, Peeters PH, Ehrnström R, Brennan P, Ferrari P, Ljungberg B, Norat T, Gunter M, Riboli E, Weiderpass E, Halkjaer J (2014) Anthropometric measures and bladder cancer risk: A prospective study in the EPIC cohort. Int J Cancer 135: 2918–2929.
    1. Steffen A, Huerta J-M, Weiderpass E, Bueno-de-Mesquita HB, May AM, Siersema PD, Kaaks R, Neamat-Allah J, Pala V, Panico S, Saieva C, Tumino R, Naccarati A, Dorronsoro M, Sánchez-Cantalejo E, Ardanaz E, Quirós JR, Ohlsson B, Johansson M, Wallner B, Overvad K, Halkjaer J, Tjønneland A, Fagherazzi G, Racine A, Clavel-Chapelon F, Key TJ, Khaw K-T, Wareham N, Lagiou P, Bamia C, Trichopoulou A, Ferrari P, Freisling H, Lu Y, Riboli E, Cross AJ, Gonzalez Ca, Boeing H (2015) General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 137: 646–657.
    1. Stolzenberg-Solomon RZ, Schairer C, Moore S, Hollenbeck A, Silverman DT (2013) Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort. Am J Clin Nutr 98: 1057–1065.
    1. White AJ, Nichols HB, Bradshaw PT, Sandler DP (2015) Overall and central adiposity and breast cancer risk in the sister study. Cancer 121: 3700–3708.
    1. World Cancer Research Fund/American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. (AICR: Washington DC, USA).
    1. World Cancer Research Fund/American Institute for Cancer Research (2011) Continuous Update Project Report. Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer.
    1. World Cancer Research Fund/American Institute for Cancer Research (2014) Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Prostate Cancer. Available at: .
    1. World Cancer Research Fund/American Institute for Cancer Research (2015. a) Continuous Update Project Report: Diet, Nutrition, Physical Activity and Gallbladder Cancer. Available at: .
    1. World Cancer Research Fund/American Institute for Cancer Research (2015. b) Continuous Update Project Report: Diet, Nutrition, Physical Activity and Liver Cancer. Available at: .

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