Impact of obesity and diabetes on the incidence of kidney and bladder cancers: a nationwide cohort study

in European Journal of Endocrinology
Correspondence should be addressed to E S Koh; Email: fiji79@catholic.ac.kr
Restricted access

Objective

Obesity and type 2 diabetes are becoming increasingly prevalent worldwide and are both associated with the increased incidence of kidney and bladder cancers. However, previous reports have provided conflicting results. We investigated the impact of body mass index (BMI) and diabetes on the incidence of both cancers in the general population.

Methods

Using nationally representative data from the Korean National Health Insurance System, 9,777,133 subjects without any malignancy who underwent health examinations in 2009 were followed to the end of 2017.

Results

After a median follow-up period of 8.32 years, 12,544 incidents of kidney cancer and 15,137 incidents of bladder cancer were identified. The hazard ratio (HR) for kidney cancer was the lowest in people with a BMI <18.5 kg/m2 (HR: 0.82, 95% confidence interval (CI): 0.72–0.94) and the highest in those with a BMI ≥30 kg/m2 (HR: 1.71, 95% CI: 1.57–1.87) compared to a reference BMI group (18.5–23 kg/m2). In subjects with diabetes, obesity was associated with increased risk of kidney cancer, although the HRs were lower than observed in those without diabetes. Otherwise, there was a reduction in risk of bladder cancer with obesity in men and the HR for bladder cancer was not affected by BMI increase in women. There was a strongly positive association between diabetes and bladder cancer in the total study population.

Conclusions

Obesity was a strong risk factors for kidney cancer, whereas the association between obesity and bladder cancer differed by gender. The subjects with diabetes had a higher risk for both cancers than those without diabetes.

 

     European Society of Endocrinology

Related Articles

Article Information

Metrics

All Time Past Year Past 30 Days
Abstract Views 76 76 76
Full Text Views 13 13 13
PDF Downloads 15 15 15

Altmetrics

Figures

  • View in gallery

    Kaplan–Meier estimates of cumulative incidence. (A) Kidney and (B) bladder cancers were among four categories divided by the presence of obesity and diabetes. The analysis was performed in an unadjusted model and both P values by log-rank were <0.001.

  • View in gallery

    Incidence rates and hazard ratios (95% confidence intervals) of kidney cancer and bladder cancer stratified by BMI and the presence of diabetes across gender. Ten categories were divided by combinations of five BMI ranges and the presence of diabetes compared with a reference nondiabetic category with BMI 18.5–23 kg/m2. Risk of kidney cancer in the total study population (A), in men (B) and in women (C). Risk of bladder cancer in the total study population (D), in men (E) and in women (F). Adjusted for age, sex, smoking, alcohol drinking, regular exercise, income status, presence of hypertension, and dyslipidemia (A and D). Adjusted for age, smoking, alcohol drinking, regular exercise, income status, presence of hypertension, and dyslipidemia (B,C,E and F).

References

  • 1

    FerlayJSoerjomataramIDikshitREserSMathersCRebeloMParkinDMFormanDBrayF. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer 2015 E359E386. (https://doi.org/10.1002/ijc.29210)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    ChowWHDongLMDevesaSS. Epidemiology and risk factors for kidney cancer. Nature Reviews Urology 2010 245257. (https://doi.org/10.1038/nrurol.2010.46)

  • 3

    GallagherEJLeRoithD. Obesity and diabetes: the increased risk of cancer and cancer-related mortality. Physiological Reviews 2015 727748. (https://doi.org/10.1152/physrev.00030.2014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    ChowWHGridleyGFraumeniJF Jr.JarvholmB. Obesity, hypertension, and the risk of kidney cancer in men. New England Journal of Medicine 2000 13051311. (https://doi.org/10.1056/NEJM200011023431804)

    • Search Google Scholar
    • Export Citation
  • 5

    LuoJMargolisKLAdamiHOLopezAMLessinLYeW & Women's Health Initiative Investigators. Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: the Women's Health Initiative (United States). American Journal of Epidemiology 2007 752759. (https://doi.org/10.1093/aje/kwm137)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    JohHKWillettWCChoE. Type 2 diabetes and the risk of renal cell cancer in women. Diabetes Care 2011 15521556. (https://doi.org/10.2337/dc11-0132)

  • 7

    LiuXSunQHouHZhuKWangQLiuHZhangQJiLLiD. The association between BMI and kidney cancer risk: an updated dose-response meta-analysis in accordance with PRISMA guideline. Medicine (Baltimore) 2018 e12860. (https://doi.org/10.1097/MD.0000000000012860)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    MacKenzieTZensMSFerraraASchnedAKaragasMR. Diabetes and risk of bladder cancer: evidence from a case-control study in New England. Cancer 2011 15521556. (https://doi.org/10.1002/cncr.25641)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    NoguchiJLLissMAParsonsJK. Obesity, physical activity and bladder cancer. Current Urology Reports 2015 74. (https://doi.org/10.1007/s11934-015-0546-2)

  • 10

    GraffRESanchezATobiasDKRodriguezDBarrisfordGWBluteMLLiYSunQPrestonMAWilsonKM Type 2 diabetes in relation to the risk of renal cell carcinoma Among men and women in two large prospective cohort studies. Diabetes Care 2018 14321437. (https://doi.org/10.2337/dc17-2518)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    PrizmentAEAndersonKEYuanJMFolsomAR. Diabetes and risk of bladder cancer among postmenopausal women in the Iowa Women's Health Study. Cancer Causes & Control 2013 603608. (https://doi.org/10.1007/s10552-012-0143-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    BenchimolEISmeethLGuttmannAHarronKMoherDPetersenISørensenHTvon ElmELanganSM & RECORD Working Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLOS Medicine 2015 e1001885. (https://doi.org/10.1371/journal.pmed.1001885)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004 157163. (https://doi.org/10.1016/S0140-6736(03)15268-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organization Technical Report Series 2000 ixii 11253.

    • Search Google Scholar
    • Export Citation
  • 15

    TsengCH. Pioglitazone and bladder cancer: a population-based study of Taiwanese. Diabetes Care 2012 278280. (https://doi.org/10.2337/dc11-1449)

  • 16

    LabochkaDMoszczukBKukwaWSzczylikCCzarneckaAM. Mechanisms through which diabetes mellitus influences renal cell carcinoma development and treatment: a review of the literature. International Journal of Molecular Medicine 2016 18871894. (https://doi.org/10.3892/ijmm.2016.2776)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    OhY. The insulin-like growth factor system in chronic kidney disease: pathophysiology and therapeutic opportunities. Kidney Research & Clinical Practice 2012 2637. (https://doi.org/10.1016/j.krcp.2011.12.005)

    • Search Google Scholar
    • Export Citation
  • 18

    TraczAFSzczylikCPortaCCzarneckaAM. Insulin-like growth factor-1 signaling in renal cell carcinoma. BMC Cancer 2016 453. (https://doi.org/10.1186/s12885-016-2437-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    XuTZhuZWangXXiaLZhangXZhongSSunFZhuYShenZ. Impact of body mass on recurrence and progression in Chinese patients with Ta, T1 urothelial bladder cancer. International Urology and Nephrology 2015 11351141. (https://doi.org/10.1007/s11255-015-1013-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    CantielloFCicioneASaloniaAAutorinoRDe NunzioCBrigantiAGandagliaGDell’OglioPCapogrossoPDamianoR. Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer: a systematic review. International Journal of Urology 2015 2232. (https://doi.org/10.1111/iju.12644)

    • Search Google Scholar
    • Export Citation
  • 21

    ZhuSXuFZhangJRuanWLaiM. Insulin-like growth factor binding protein-related protein 1 and cancer. Clinica Chimica Acta; International Journal of Clinical Chemistry 2014 2332. (https://doi.org/10.1016/j.cca.2014.01.037)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    ChoiWPortenSKimSWillisDPlimackERHoffman-CensitsJRothBChengTTranMLeeIL Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014 152165. (https://doi.org/10.1016/j.ccr.2014.01.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    GildPEhdaieBKluthLA. Effect of obesity on bladder cancer and renal cell carcinoma incidence and survival. Current Opinion in Urology 2017 409414. (https://doi.org/10.1097/MOU.0000000000000425)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Beebe-DimmerJLColtJSRuterbuschJJKeeleGRPurdueMPWacholderSGraubardBIDavisFChowWHSchwartzKL. Body mass index and renal cell cancer: the influence of race and sex. Epidemiology 2012 821828. (https://doi.org/10.1097/EDE.0b013e31826b7fe9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    AntoniSFerlayJSoerjomataramIZnaorAJemalABrayF. Bladder cancer incidence and mortality: a global overview and recent trends. European Urology 2017 96108. (https://doi.org/10.1016/j.eururo.2016.06.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    ChenHFChenSWChangYHLiCY. Risk of malignant neoplasms of kidney and bladder in a cohort study of the diabetic population in Taiwan With age, sex, and geographic area stratifications. Medicine (Baltimore) 2015 e1494. (https://doi.org/10.1097/MD.0000000000001494)

    • Search Google Scholar
    • Export Citation
  • 27

    LiuSLiYLinTFanXLiangYHeemannU. High dose human insulin and insulin glargine promote T24 bladder cancer cell proliferation via PI3K-independent activation of Akt. Diabetes Research & Clinical Practice 2011 177182. (https://doi.org/10.1016/j.diabres.2010.11.009)

    • Search Google Scholar
    • Export Citation
  • 28

    MetalliDLovatFTripodiFGenuaMXuSQSpinelliMAlberghinaLVanoniMBaffaRGomellaLG The insulin-like growth factor receptor I promotes motility and invasion of bladder cancer cells through Akt- and mitogen-activated protein kinase-dependent activation of paxillin. American Journal of Pathology 2010 29973006. (https://doi.org/10.2353/ajpath.2010.090904)

    • Search Google Scholar
    • Export Citation
  • 29

    TsengCH. Human insulin does not increase bladder cancer risk. PLOS ONE 2014 e86517. (https://doi.org/10.1371/journal.pone.0086517)

  • 30

    FangHYaoBYanYXuHLiuYTangHZhouJCaoLWangWZhangJ Diabetes mellitus increases the risk of bladder cancer: an updated meta-analysis of observational studies. Diabetes Technology & Therapeutics 2013 914922. (https://doi.org/10.1089/dia.2013.0131)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    TsengCH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia 2011 20092015. (https://doi.org/10.1007/s00125-011-2171-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    HsiehJJPurdueMPSignorettiSSwantonCAlbigesLSchmidingerMHengDYLarkinJFicarraV. Renal cell carcinoma. Nature Reviews. Disease Primers 2017 17009. (https://doi.org/10.1038/nrdp.2017.9)

    • PubMed
    • Search Google Scholar
    • Export Citation

PubMed

Google Scholar