Abstract
Objective
A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors.
Methods
We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50–71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression.
Results
During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI = 0.64, 0.74) and 0.71 (95% CI = 0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR = 0.41; 95% CI = 0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer.
Conclusion
Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk.
Similar content being viewed by others
References
Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW (2006) Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999–2002. Diabetes Care 29:1263–1268
Flegal KM, Carroll MD, Ogden CL, Johnson CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. Jama 288:1723–1727
CDC (2005) Trends in leisure-time physical inactivity by age, sex, and race/ethnicity–United States, 1994–2004. MMWR Morb Mortal Wkly Rep 54:991–994
U.S. Census Bureau, Population Division (2006) Age Data. Available at: http://www.census.gov/population/www/socdemo/age.html. Accessed June 30 2006
Yach D, Stuckler D, Brownell KD (2006) Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med 12:62–66
O’Mara BA, Byers T, Schoenfeld E (1985) Diabetes mellitus and cancer risk: a multisite case-control study. J Chronic Dis 38:435–441
Bonovas S, Filioussi K, Tsantes A (2004) Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia 47:1071–1078
Giovannucci E (2003) Nutrition, insulin, insulin-like growth factors and cancer. Horm Metab Res 35:694–704
Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, Hayes FJ (2005) Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 90:2636–2641
American Cancer Society (2005) Cancer facts and figures 2005. American Cancer Society, Atlanta
Gronberg H (2003) Prostate cancer epidemiology. Lancet 361:859–864
Schatzkin A, Subar AF, Thompson FE, Harlan LC, Tangrea J, Hollenbeck AR, Hurwitz PE, Coyle L, Schussler N, Michaud DS, Freedman LS, Brown CC, Midthune D, Kipnis V (2001) Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am J Epidemiol 154:1119–1125
Michaud DS, Midthune D, Hermansen S, Leitzmann MF, Harlan L, Kipnis V, Schatzkin A (2005) Comparison of cancer registry case ascertainment with SEER estimates and self-reporting in a subset of the NIH-AARP Diet and Health Study. J Registry Manage 32:70–75
NAACR (2002) Standards for completeness, quality, analysis, and management of data, vol. 3. North American Association of Central Disease Registries
AJCC (1997) Cancer staging manual. Lippincott-Raven, Philadelphia, PA
Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, Wiedmeyer HM, Byrd-Holt DD (1998) Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 21:518–524
Wilson EB, Maher HC (1932) Cancer and tuberculosis with some comments on cancer and other diseases. Am J Cancer 16:227–250
Glicksman AS, Rawson RW (1956) Diabetes and altered carbohydrate metabolism in patients with cancer. Cancer 9:1127–1134
Bell ET (1957) Carcinoma of the pancreas. I. A clinical and pathologic study of 600 necropsied patients. II. The relation of carcinoma of pancreas to diabetes mellitus. Am J Pathol 33:499–523
Lancaster HO, Maddox JK (1958) Diabetic mortality in Australia. Australias Ann Med 7:145–150
Steele JM, Sperling WL (1961) Relationship between diabetes mellitus and cancer. A study of the records for eight years at the Robert Packer Hospital. Guthrie Clin Bull 30:63–67
Kessler II (1970) Cancer mortality among diabetics. J Nat Cancer Inst 44:673–686
Wynder EL, Mabuchi K, Whitmore WF, Jr (1971) Epidemiology of cancer of the prostate. Cancer 28:344–360
Henderson BE, Bogdanoff E, Gerkins VR, SooHoo J, Arthur M (1974) Evaluation of cancer risk factors in a retirement community. Cancer Research 34:1045–1048
Ragozzino M, Melton LJ 3rd, Chu CP, Palumbo PJ (1982) Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chronic Dis 35:13–19
Mishina T, Watanabe H, Araki H, Nakao M (1985) Epidemiological study of prostatic cancer by matched-pair analysis. Prostate 6:423–436
Checkoway H, DiFerdinando G, Hulka BS, Mickey DD (1987) Medical, life-style, and occupational risk factors for prostate cancer. Prostate 10:79–88
Thompson MM, Garland C, Barrett-Connor E, Khaw KT, Friedlander NJ, Wingard DL (1989) Heart disease risk factors, diabetes, and prostatic cancer in an adult community. Am J Epidemiol 129:511–517
Levine W, Dyer AR, Shekelle RB, Schoenberger JA, Stamler J (1990) Post-load plasma glucose and cancer mortality in middle-aged men and women. 12-year follow-up findings of the Chicago Heart Association Detection Project in Industry. Am J Epidemiol 131:254–262
Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, Persson I (1991) Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2:307–314
Smith GD, Egger M, Shipley MJ, Marmot MG (1992) Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. Am J Epidemiol 136:1110–1114
Coughlin SS, Neaton JD, Sengupta A (1996) Cigarette smoking as a predictor of death from prostate cancer in 348,874 men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol 143:1002–1006
Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes Mellitus as a Predictor of Cancer Mortality in a Large Cohort of US Adults. Am J Epidemiol 159:1160–1167
Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, Borch-Johnsen K, Olsen JH (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 89:1360–1365
Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A (1997) Cancer and diabetes–a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 241:471–475
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1998) Diabetes mellitus and risk of prostate cancer (United States). Cancer Causes & Control 9:3–9
Weiderpass E, Ye W, Vainio H, Kaaks R, Adami HO (2002) Reduced risk of prostate cancer among patients with diabetes mellitus. Int J Cancer 102:258–261
Zhu K, Lee IM, Sesso HD, Buring JE, Levine RS, Gaziano JM (2004) History of diabetes mellitus and risk of prostate cancer in physicians. Am J Epidemiol 159:978–982
Rodriguez C, Patel AV, Mondul AM, Jacobs EJ, Thun MJ, Calle EE (2005) Diabetes and risk of prostate cancer in a prospective cohort of US men. Am J Epidemiol 161:147–152
Gonzalez-Perez A, Garcia Rodriguez LA (2005) Prostate cancer risk among men with diabetes mellitus (Spain). Cancer Causes Control 16:1055–1058
La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P (1994) A case-control study of diabetes mellitus and cancer risk. Br J Cancer 70:950–953
Rosenberg DJ, Neugut AI, Ahsan H, Shea S (2002) Diabetes mellitus and the risk of prostate cancer. Cancer Invest 20:157–165
Coker AL, Sanderson M, Zheng W, Fadden MK (2004) Diabetes mellitus and prostate cancer risk among older men: population-based case-control study. Br J Cancer 90:2171–2175
Lightfoot N, Conlon M, Kreiger N, Sass-Kortsak A, Purdham J, Darlington G (2004) Medical history, sexual, and maturational factors and prostate cancer risk. Ann Epidemiol 14:655–662
Steenland K, Nowlin S, Palu S (1995) Cancer incidence in the National Health and Nutrition Survey I. Follow-up data: diabetes, cholesterol, pulse and physical activity. Cancer Epidemiol Biomarkers Prev 4:807–811
Will JC, Vinicor F, Calle EE (1999) Is diabetes mellitus associated with prostate cancer incidence and survival? Epidemiology 10:313–318
Hsieh CC, Thanos A, Mitropoulos D, Deliveliotis C, Mantzoros CS, Trichopoulos D (1999) Risk factors for prostate cancer: a case-control study in Greece. Int J Cancer 80:699–703
Tavani A, Gallus S, Bosetti C, Tzonou A, Lagiou P, Negri E, Trichopoulos D, La Vecchia C (2002) Diabetes and the risk of prostate cancer. Eur J Cancer Prev 11:125–128
Rousseau MC, Parent ME, Pollak MN, Siemiatycki J (2006) Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal, Canada. Int J Cancer 118:2105–2109
Hammarsten J, Hogstedt B (2004) Clinical, haemodynamic, anthropometric, metabolic and insulin profile of men with high-stage and high-grade clinical prostate cancer. Blood Press 13:47–55
Batty GD, Shipley MJ, Marmot M, Smith GD (2004) Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study. Cancer Causes Control 15:873–881
Tavani A, Gallus S, Bertuzzi M, Dal Maso L, Zucchetto A, Negri E, Franceschi S, Ramazzotti V, Montella M, La Vecchia C (2005) Diabetes mellitus and the risk of prostate cancer in Italy. Eur Urol 47:313–317; discussion 317
Kasper JS, Giovannucci E (2006) A Meta-analysis of Diabetes Mellitus and the Risk of Prostate Cancer. Cancer Epidemiol Biomarkers Prev 15:2056–2062
Chan JM, Latini DM, Cowan J, Duchane J, Carroll PR (2005) History of diabetes, clinical features of prostate cancer, and prostate cancer recurrence-data from CaPSURE (United States). Cancer Causes Control 16:789–797
Kane CJ, Bassett WW, Sadetsky N, Silva S, Wallace K, Pasta DJ, Cooperberg MR, Chan JM, Carroll PR (2005) Obesity and prostate cancer clinical risk factors at presentation: data from CaPSURE. J Urol 173:732–736
Centers for Disease Control and Prevention (2006), National Diabetes Surveillance Program Age at Diagnosis Among Adults Aged 18–70 Years. Available at: http://www.cdc.gov/diabetes/statistics/age. Accessed June 30 2006
Burke JP, Jacobson DJ, McGree ME, Roberts RO, Girman CJ, Lieber MM, Jacobsen SJ (2006) Diabetes and benign prostatic hyperplasia progression in Olmsted County, Minnesota. Urology 67:22–25
Okura Y, Urban LH, Mahoney DW, Jacobsen SJ, Rodeheffer RJ (2004) Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure. J Clin Epidemiol 57:1096–1103
Hsing AW, Chokkalingam AP (2006) Prostate cancer epidemiology. Front Biosci 11:1388–1413
Regensteiner JG, Shetterly SM, Mayer EJ, Eckel RH, Haskell WL, Baxter J, Hamman RF (1995) Relationship between habitual physical activity and insulin area among individuals with impaired glucose tolerance. The San Luis Valley Diabetes Study. Diabetes Care 18:490–497
Daly W, Seegers CA, Rubin DA, Dobridge JD, Hackney AC (2005) Relationship between stress hormones and testosterone with prolonged endurance exercise. Eur J Appl Physiol 93:375–380
Hoffman MA, DeWolf WC, Morgentaler A (2000) Is low serum free testosterone a marker for high grade prostate cancer? J Urol 163:824–827
Platz EA, Leitzmann MF, Rifai N, Kantoff PW, Chen YC, Stampfer MJ, Willett WC, Giovannucci E (2005) Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev 14:1262–1269
Acknowledgments
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We thank Leslie Carroll at Information Management Services for data support and Tawanda Roy at the Nutritional Epidemiology Branch for research assistance. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System under contract to the Department of Health (DOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the contractor or DOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Calton, B.A., Chang, S.C., Wright, M.E. et al. History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study. Cancer Causes Control 18, 493–503 (2007). https://doi.org/10.1007/s10552-007-0126-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-007-0126-y