Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study

Authors

  • Martin Støyten Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway
  • Tore Knutsen Department of Urology, University Hospital of North Norway, Tromsø, Norway
  • Einar Stikbakke Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway
  • Ingvild Agledahl Department of Urology, University Hospital of North Norway, Tromsø, Norway
  • Tom Wilsgaard Institute of Community Medicine, UIT-The Arctic University, Tromsø, Norway
  • Anne Elise Eggen Institute of Community Medicine, UIT-The Arctic University, Tromsø, Norway
  • Elin Richardsen Department of Pathology, University Hospital of North Norway, Tromsø, Norway; Department of Medical Biology, UIT – The Arctic University, Tromsø, Norway
  • Edward Giovannucci Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  • Inger Thune Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Oslo University Hospital, Norway
  • Hege S. Haugnes Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway

DOI:

https://doi.org/10.2340/1651-226X.2024.32953

Keywords:

prostate cancer, incidence, mortality, body mass index, weight change, obesity

Abstract

Background: Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results.

Methods: In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994–2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality.

Results: At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39–6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30–0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03–2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11–3.70).

Interpretation: In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.

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Author Biographies

Martin Støyten, Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway

Martin Støyten and Tore Knutsen have shared first authorship.

Inger Thune, Institute of Clinical Medicine, UIT – The Arctic University, Tromsø, Norway; Insitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Oslo University Hospital, Norway

Inger THune and Hege S Haugnes have shared last authorship

References

Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 91 million participants. Lancet. 2011;377(9765):557–67.

https://doi.org/10.1016/S0140-6736(10)62037-5 DOI: https://doi.org/10.1016/S0140-6736(10)62037-5

Meyer HE, Tverdal A. Development of body weight in the Norwegian population. Prostaglandins Leukot Essent Fatty Acids. 2005;73(1): 3–7.

https://doi.org/10.1016/j.plefa.2005.04.003 DOI: https://doi.org/10.1016/j.plefa.2005.04.003

Midthjell K, Lee CM, Langhammer A, et al. Trends in overweight and obesity over 22 years in a large adult population: the HUNT Study, Norway. Clin Obes. 2013;3(1–2):12–20.

https://doi.org/10.1111/cob.12009 DOI: https://doi.org/10.1111/cob.12009

Jacobsen BK, Aars NA. Changes in body mass index and the prevalence of obesity during 1994–2008: repeated cross-sectional surveys and longitudinal analyses. The Tromsø Study. BMJ Open. 2015;5(6):e007859.

https://doi.org/10.1136/bmjopen-2015-007859 DOI: https://doi.org/10.1136/bmjopen-2015-007859

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

https://doi.org/10.3322/caac.21660 DOI: https://doi.org/10.3322/caac.21660

Wilson RL, Taaffe DR, Newton RU, Hart NH, Lyons-Wall P, Galvão DA. Obesity and prostate cancer: a narrative review. Crit Rev Oncol Hematol. 2022;169:103543.

https://doi.org/10.1016/j.critrevonc.2021.103543 DOI: https://doi.org/10.1016/j.critrevonc.2021.103543

Gandaglia G, Leni R, Bray F, et al. Epidemiology and prevention of prostate cancer. Eur Urol Oncol. 2021;4(6):877–92.

https://doi.org/10.1016/j.euo.2021.09.006 DOI: https://doi.org/10.1016/j.euo.2021.09.006

Kazmi N, Haycock P, Tsilidis K, Lynch BM, Truong T. Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79148 prostate-cancer cases and 61106 controls. Int J Epidemiol. 2020;49(2):587–96.

https://doi.org/10.1093/ije/dyz235 DOI: https://doi.org/10.1093/ije/dyz235

Onerup A, Mehlig K, Af Geijerstam A, et al. Associations between BMI in youth and site‐specific cancer in men – a cohort study with regis-ter linkage. Obesity. 2023;32(2):376–89.

https://doi.org/10.1002/oby.23942 DOI: https://doi.org/10.1002/oby.23942

Rivera-Izquierdo M, Pérez de Rojas J, Martínez-Ruiz V, et al. Obesity as a risk factor for prostate cancer mortality: a systematic review and dose-response meta-analysis of 280,199 patients. Cancers. 2021;13(16):4169.

https://doi.org/10.3390/cancers13164169 DOI: https://doi.org/10.3390/cancers13164169

Zhang X, Zhou G, Sun B, et al. Impact of obesity upon prostate cancer-associated mortality: a meta‑analysis of 17 cohort studies. Oncol Lett. 2015;9(3):1307–12.

https://doi.org/10.3892/ol.2014.2841 DOI: https://doi.org/10.3892/ol.2014.2841

Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63(5):800–9.

https://doi.org/10.1016/j.eururo.2012.11.013 DOI: https://doi.org/10.1016/j.eururo.2012.11.013

Dickerman BA, Ahearn TU, Giovannucci E, et al. Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer. Int J Cancer. 2017;141(5):933–44.

https://doi.org/10.1002/ijc.30803 DOI: https://doi.org/10.1002/ijc.30803

Kelly SP, Lennon H, Sperrin M, et al. Body mass index trajectories across adulthood and smoking in relation to prostate cancer risks: the NIH-AARP Diet and Health Study. Int J Epidemiol. 2019;48(2): 464–73.

https://doi.org/10.1093/ije/dyy219 DOI: https://doi.org/10.1093/ije/dyy219

Genkinger J, Wu K, Wang M, et al. Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer. Ann Oncol. 2020;31(1):103–114.

https://doi.org/10.1016/j.annonc.2019.09.007 DOI: https://doi.org/10.1016/j.annonc.2019.09.007

Fang X, Wei J, He X, et al. Q uantitative association between body mass index and the risk of cancer: a global Meta‐analysis of prospective cohort studies. Int J Cancer. 2018;143(7):1595–603.

https://doi.org/10.1002/ijc.31553 DOI: https://doi.org/10.1002/ijc.31553

Markozannes G, Tzoulaki I, Karli D, et al. Diet, body size, physical activity and risk of prostate cancer: an umbrella review of the evidence. Eur J Cancer. 2016;69:61–9.

https://doi.org/10.1016/j.ejca.2016.09.026 DOI: https://doi.org/10.1016/j.ejca.2016.09.026

Harrison S, Tilling K, Turner EL, et al. Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen. Cancer Causes Contr. 2020;31(5):431–49.

https://doi.org/10.1007/s10552-020-01291-3 DOI: https://doi.org/10.1007/s10552-020-01291-3

Song M, Willett WC, Hu FB, et al. Trajectory of body shape across the lifespan and cancer risk. Int J Cancer. 2016;138(10):2383–95.

https://doi.org/10.1002/ijc.29981 DOI: https://doi.org/10.1002/ijc.29981

Wang Q-L, Song M, Clinton SK, et al. Longitudinal trajectories of lifetime body shape and prostate cancer angiogenesis. Eur J Epidemiol. 2022;37(3):261–70.

https://doi.org/10.1007/s10654-021-00838-1 DOI: https://doi.org/10.1007/s10654-021-00838-1

Finley DS, Calvert VS, Inokuchi J, et al. Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness. J Urol. 2009;182(4):1621–7.

https://doi.org/10.1016/j.juro.2009.06.015 DOI: https://doi.org/10.1016/j.juro.2009.06.015

Banez LL, Hamilton RJ, Partin AW, et al. Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer. JAMA. 2007;298(19):2275–80.

https://doi.org/10.1001/jama.298.19.2275 DOI: https://doi.org/10.1001/jama.298.19.2275

Center MM, Jemal A, Lortet-Tieulent J, et al. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012;61(6):1079–92.

https://doi.org/10.1016/j.eururo.2012.02.054 DOI: https://doi.org/10.1016/j.eururo.2012.02.054

Zhou CK, Check DP, Lortet‐Tieulent J, et al. Prostate cancer incidence in 43 populations worldwide: an analysis of time trends overall and by age group. Int J Cancer. 2016;138(6):1388–400.

https://doi.org/10.1002/ijc.29894 DOI: https://doi.org/10.1002/ijc.29894

Wang K, Chen X, Gerke TA, Bird VY, Ghayee HK, Prosperi M. BMI trajectories and risk of overall and grade‐specific prostate cancer: an observational cohort study among men seen for prostatic conditions. Cancer Med. 2018;7(10):5272–80.

https://doi.org/10.1002/cam4.1747 DOI: https://doi.org/10.1002/cam4.1747

Keum N, Greenwood DC, Lee DH, et al. Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J Natl Cancer Inst. 2015;107(2):djv088.

https://doi.org/10.1093/jnci/djv088 DOI: https://doi.org/10.1093/jnci/djv088

Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njølstad I. Cohort profile: the Tromso Study. Int J Epidemiol. 2012;41(4):961–7.

https://doi.org/10.1093/ije/dyr049 DOI: https://doi.org/10.1093/ije/dyr049

Eggen AE, Mathiesen EB, Wilsgaard T, Jacobsen BK, Njølstad I. The sixth survey of the Tromsø study (Tromsø 6) in 2007–08: collaborative research in the interface between clinical medicine and epidemiology: study objectives, design, data collection procedures, and attendance in a multipurpose population-based health survey. Scand J Public Health. 2013;41(1):65–80.

https://doi.org/10.1177/1403494812469851 DOI: https://doi.org/10.1177/1403494812469851

Brækkan SK, Hald EM, Mathiesen EB, et al. Competing risk of atherosclerotic risk factors for arterial and venous thrombosis in a general population: the Tromsø study. Arterioscler Thromb Vasc Biol. 2012;32(2):487–91.

https://doi.org/10.1161/ATVBAHA.111.237545 DOI: https://doi.org/10.1161/ATVBAHA.111.237545

Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA. The 2014 International Society of Urological Pathology (ISUP) Consen-sus Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 2016;40(2):244–52.

https://doi.org/10.1097/PAS.0000000000000530 DOI: https://doi.org/10.1097/PAS.0000000000000530

Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9.

https://doi.org/10.1002/cncr.25537 DOI: https://doi.org/10.1002/cncr.25537

D’Amico AV, Whittington R, Malkowicz SB, et al. Predicting prostate specific antigen outcome preoperatively in the prostate specific anti-gen era. J Urol. 2001;166(6):2185–8.

https://doi.org/10.1016/S0022-5347(05)65531-0 DOI: https://doi.org/10.1016/S0022-5347(05)65531-0

Stevens J, Truesdale KP, McClain JE, Cai J. The definition of weight maintenance. Int J Obes. 2006;30(3):391–9.

https://doi.org/10.1038/sj.ijo.0803175 DOI: https://doi.org/10.1038/sj.ijo.0803175

Kvåle R, Myklebust T, Engholm G, Heinävaara S, Wist E, Møller B. Prostate and breast cancer in four Nordic countries: a comparison of incidence and mortality trends across countries and age groups 1975–2013. Int J Cancer. 2017;141(11):2228–42.

https://doi.org/10.1002/ijc.30924 DOI: https://doi.org/10.1002/ijc.30924

Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.

https://doi.org/10.1016/j.ejca.2018.07.005 DOI: https://doi.org/10.1016/j.ejca.2018.07.005

Kvåle R, Møller B, Angelsen A, et al. Regional trends in prostate cancer incidence, treatment with curative intent and mortality in Norway 1980–2007. Cancer Epidemiol. 2010;34(4):359–67.

https://doi.org/10.1016/j.canep.2010.04.017 DOI: https://doi.org/10.1016/j.canep.2010.04.017

Albertsen PC, Bjerner LJ, Pasovic L, et al. Opportunistic prostate-specific antigen testing in Norwegian men: a public health challenge. BJU Int. 2024;133(1):104–11.

https://doi.org/10.1111/bju.16211 DOI: https://doi.org/10.1111/bju.16211

Discacciati A, Orsini N, Andersson S-O, Andrén O, Johansson J, Wolk A. Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study. Br J Cancer. 2011;105(7):1061–8.

https://doi.org/10.1038/bjc.2011.319 DOI: https://doi.org/10.1038/bjc.2011.319

Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78.

https://doi.org/10.1016/S0140-6736(08)60269-X DOI: https://doi.org/10.1016/S0140-6736(08)60269-X

MacInnis RJ, English DR. Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Caus-es Contr. 2006;17(8):989–1003.

https://doi.org/10.1007/s10552-006-0049-z DOI: https://doi.org/10.1007/s10552-006-0049-z

Fang Z, Giovannucci EL. The timing of adiposity and changes in the life course on the risk of cancer. Cancer Metastasis Rev. 2022;41(3):471–89.

https://doi.org/10.1007/s10555-022-10054-2 DOI: https://doi.org/10.1007/s10555-022-10054-2

Yuan C, Jian Z, Feng S, et al. Do obesity-related traits affect prostate cancer risk through serum testosterone? A Mendelian randomization study. Cancers. 2023;15(19):4884.

https://doi.org/10.3390/cancers15194884 DOI: https://doi.org/10.3390/cancers15194884

Ramalingam S, Ramamurthy VP, Njar VCO. Dissecting major signaling pathways in prostate cancer development and progression: mecha-nisms and novel therapeutic targets. J Steroid Biochem Mol Biol. 2017;166:16–27.

https://doi.org/10.1016/j.jsbmb.2016.07.006 DOI: https://doi.org/10.1016/j.jsbmb.2016.07.006

Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and pros-tate disease, via aberrant ER-α and GPER signalling. Mol Cell Endocrinol. 2012;351(2):269–78.

https://doi.org/10.1016/j.mce.2011.12.017 DOI: https://doi.org/10.1016/j.mce.2011.12.017

Massillo C, Dalton GN, Porretti J, et al. CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome. Int J Cancer. 2019;144(5): 1115–27.

https://doi.org/10.1002/ijc.31773 DOI: https://doi.org/10.1002/ijc.31773

Omran A, Leca BM, Oštarijaš E, et al. Metabolic syndrome is associated with prostate enlargement: a systematic review, meta-analysis, and meta-regression on patients with lower urinary tract symptom factors. Ther Adv Endocrinol Metab. 2021;12:1–29 https://doi.org/10.1177/20420188211066210 DOI: https://doi.org/10.1177/20420188211066210

Chen W, Man S, Wang B, Kadeerhan G, Huang X. Metabolically healthy obesity is associated with increased risk of lower urinary tract symptoms secondary to benign prostatic hyperplasia: a cohort study of C hinese elderly males. LUTS: Low Urin Tract Symptoms. 2022;14(3):170–7.

https://doi.org/10.1111/luts.12420 DOI: https://doi.org/10.1111/luts.12420

Al-Zubaidi M, Hawks C, Fernando S, et al. Relationship between lower urinary tract symptoms (LUTS) and prostate cancer: a persistent myth. J Clin Urol. 2023:20514158231170420. 2023;0(0).

https://doi.org/10.1177/20514158231170420 DOI: https://doi.org/10.1177/20514158231170420

Chandra Engel J, Palsdottir T, Aly M, et al. Lower urinary tract symptoms (LUTS) are not associated with an increased risk of prostate cancer in men 50–69 years with PSA≥ 3 ng/ml. Scand J Urol. 2020;54(1):1–6.

https://doi.org/10.1080/21681805.2019.1703806 DOI: https://doi.org/10.1080/21681805.2019.1703806

Luo R, Chen Y, Ran K, Jiang Q. Effect of obesity on the prognosis and recurrence of prostate cancer after radical prostatectomy: a meta-analysis. Transl Androl Urol. 2020;9(6):2713.

https://doi.org/10.21037/tau-20-1352 DOI: https://doi.org/10.21037/tau-20-1352

Wilsgaard T, Jacobsen BK, Mathiesen EB, Njølstad I. Weight loss and mortality: a gender-specific analysis of the Tromsø study. Gend Med. 2009;6(4):575–86.

https://doi.org/10.1016/j.genm.2009.12.003 DOI: https://doi.org/10.1016/j.genm.2009.12.003

Larsen IK, Småstuen M, Johannesen TB, et al. Data quality at the Cancer Registry of Norway: an overview of comparability, completeness, validity and timeliness. Eur J Cancer. 2009;45(7):1218–31.

https://doi.org/10.1016/j.ejca.2008.10.037 DOI: https://doi.org/10.1016/j.ejca.2008.10.037

Published

2024-04-09

How to Cite

Støyten, M., Knutsen, T., Stikbakke, E., Agledahl, I., Wilsgaard, T., Eggen, A. E., Richardsen, E., Giovannucci, E., Thune, I., & Haugnes, H. S. (2024). Excess weight, weight gain, and prostate cancer risk and prognosis: the PROCA-life study. Acta Oncologica, 63(1), 154–163. https://doi.org/10.2340/1651-226X.2024.32953

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