The association of metformin use with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study
- 161 Downloads
Abstract
Purpose
Metformin has been associated with a reduced incidence of prostate cancer and improved prostate cancer outcomes. However, whether race modifies the association between metformin use and prostate cancer aggressiveness remains uncertain. The association between metformin use and prostate cancer aggressiveness was examined separately in Black Americans (Blacks) and White Americans (Whites).
Methods
The study population consisted of 305 Black and 195 White research participants with incident prostate cancer and self-reported diabetes from the North Carolina–Louisiana Prostate Cancer Project. High-aggressive prostate cancer was defined using a composite measure of Gleason sum, prostate-specific antigen, and clinical stage. Multivariable logistic regression was used to assess the association between metformin use and high-aggressive prostate cancer at diagnosis, separately among Whites and Blacks, with adjustment for age, screening history, site, education, insurance, and body mass index.
Results
Metformin use was associated positively with high-aggressive prostate cancer in Blacks (OR 2.01; 95% CI 1.05, 3.83). By contrast, a weak inverse association between metformin use and high-aggressive prostate cancer was found in Whites (OR 0.80, 95% CI 0.34, 1.85).
Conclusions
The association between metformin use and prostate cancer aggressiveness may be modified by race.
Keywords
Prostate cancer Metformin Black Americans Aggressiveness PCaPNotes
Acknowledgments
The North Carolina–Louisiana Prostate Cancer Project (PCaP) is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. The authors thank the staff, advisory committees, and research subjects participating in the PCaP study for their important contributions. Dr. Khan was supported by the National Cancer Institute Grant T32190194 (PI, Colditz) and Department of Defence Grant PC170130. Drs. Khan and Drake are supported by the Foundation for Barnes-Jewish Hospital and Siteman Cancer Center. This content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Health (NIH).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Research involving animal and human participants
This article does not contain any studies with animals performed by any of the authors.
References
- 1.Surveillance E, Results E (2017) https://seer.cancer.gov/statfacts/html/prost.html. Accessed 6 Oct 2017
- 2.U.S. Department of Health and Human Services. Diabetes and Americans A (2017) https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=18. Accessed 19 Sept 2017
- 3.Xu J, Murphy SL, Kochanek KD, Arias E (2016) Mortality in the United States, 2015. NCHS Data Brief 267:1–8Google Scholar
- 4.Papanas N, Maltezos E, Mikhailidis DP (2010) Metformin and cancer: licence to heal? Exp Opin Investig Drugs 19(8):913–917. https://doi.org/10.1517/13543784.2010.499122 CrossRefGoogle Scholar
- 5.Raval AD, Mattes MD, Madhavan S, Pan X, Wei W, Sambamoorthi U (2016) Association between metformin use and cancer stage at diagnosis among elderly Medicare beneficiaries with preexisting type 2 diabetes mellitus and incident prostate cancer. J Diabetes Res 2016:2656814. https://doi.org/10.1155/2016/2656814 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Khan S, Cai J, Nielsen ME et al (2016) The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study. Cancer Causes Control 27(12):1475–1485. https://doi.org/10.1007/s10552-016-0828-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Khan S, Cai J, Nielsen ME et al (2017) The association of diabetes and obesity with prostate cancer progression: HCaP-NC. Prostate 77(8):878–887. https://doi.org/10.1002/pros.23342 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Schroeder JC, Bensen JT, Su LJ et al (2006) The North Carolina-Louisiana Prostate Cancer Project (PCaP): methods and design of a multidisciplinary population-based cohort study of racial differences in prostate cancer outcomes. Prostate 66(11):1162–1176. https://doi.org/10.1002/pros.20449 CrossRefPubMedGoogle Scholar
- 9.Weinberg CR, Sandler DP (1991) Randomized recruitment in case–control studies. Am J Epidemiol 134(4):421–432CrossRefGoogle Scholar
- 10.DeFronzo RA (2010) Current issues in the treatment of type 2 diabetes. Overview of newer agents: where treatment is going. Am J Med 123(3 Suppl):S38–S48. https://doi.org/10.1016/j.amjmed.2009.12.008 CrossRefPubMedGoogle Scholar
- 11.Albanes D, Weinstein SJ, Wright ME et al (2009) Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 101(18):1272–1279CrossRefGoogle Scholar
- 12.VanderWeele TJ (2009) On the distinction between interaction and effect modification. Epidemiology 20(6):863–871. https://doi.org/10.1097/EDE.0b013e3181ba333c CrossRefPubMedGoogle Scholar
- 13.He XX, Tu SM, Lee MH, Yeung SC (2011) Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol 22(12):2640–2645. https://doi.org/10.1093/annonc/mdr020 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Deng D, Yang Y, Tang X et al (2015) Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta-analysis. Diabetes/Metab Res Rev. https://doi.org/10.1002/dmrr.2645 CrossRefGoogle Scholar
- 15.Danzig MR, Kotamarti S, Ghandour RA et al (2015) Synergism between metformin and statins in modifying the risk of biochemical recurrence following radical prostatectomy in men with diabetes. Prostate Cancer Prostatic Dis 18(1):63–68. https://doi.org/10.1038/pcan.2014.47 CrossRefPubMedGoogle Scholar
- 16.Margel D, Urbach D, Lipscombe LL et al (2013) Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst 105(15):1123–1131. https://doi.org/10.1093/jnci/djt170 CrossRefPubMedGoogle Scholar
- 17.Soranna D, Scotti L, Zambon A et al (2012) Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. The Oncologist 17(6):813–822. https://doi.org/10.1634/theoncologist.2011-0462 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Wright JL, Stanford JL (2009) Metformin use and prostate cancer in Caucasian men: results from a population-based case–control study. Cancer Causes Control 20(9):1617–1622. https://doi.org/10.1007/s10552-009-9407-y CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Florez JC (2014) It’s not black and white: individualizing metformin treatment in type 2 diabetes. J Clin Endocrinol Metab 99(9):3125–3128. https://doi.org/10.1210/jc.2014-733 CrossRefPubMedGoogle Scholar
- 20.Zhou K, Donnelly L, Yang J et al (2014) Heritability of variation in glycaemic response to metformin: a genome-wide complex trait analysis. Lancet Diabetes Endocrinol 2(6):481–487. https://doi.org/10.1016/s2213-8587(14)70050-6 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Williams LK, Padhukasahasram B, Ahmedani BK et al (2014) Differing effects of metformin on glycemic control by race-ethnicity. J Clin Endocrinol Metab 99(9):3160–3168. https://doi.org/10.1210/jc.2014-1539 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Trinacty CM, Adams AS, Soumerai SB et al (2009) Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study. BMC Health Serv Res 9:24. https://doi.org/10.1186/472-6963-9-24 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Shenolikar RA, Balkrishnan R, Camacho FT, Whitmire JT, Anderson RT (2006) Race and medication adherence in Medicaid enrollees with type-2 diabetes. J Natl Med Assoc 98(7):1071–1077PubMedPubMedCentralGoogle Scholar
- 24.Adams AS, Trinacty CM, Zhang F et al (2008) Medication adherence and racial differences in A1C control. Diabetes Care 31(5):916–921. https://doi.org/10.2337/dc07-1924 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Grant RW, Wexler DJ, Watson AJ et al (2007) How doctors choose medications to treat type 2 diabetes: a national survey of specialists and academic generalists. Diabetes Care 30(6):1448–1453. https://doi.org/10.2337/dc06-2499 CrossRefPubMedGoogle Scholar
- 26.Goonesekera SD, Yang MH, Hall SA, Fang SC, Piccolo RS, McKinlay JB (2015) Racial ethnic differences in type 2 diabetes treatment patterns and glycaemic control in the Boston Area Community Health Survey. BMJ Open 5(5):e007375. https://doi.org/10.1136/bmjopen-2014-007375 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Perez A, Elrod S, Sanchez J (2016) A comparison of the use and quality of antidiabetic medication regimens between non-Hispanic Black and white adults with uncontrolled type 2 diabetes in the US: NHANES 2003–2012. Diabetes Educ 42(2):234–242. https://doi.org/10.1177/0145721716628650 CrossRefPubMedGoogle Scholar
- 28.Tan X, Feng X, Chang J, Higa G, Wang L, Leslie D (2016) Oral antidiabetic drug use and associated health outcomes in cancer patients. J Clin Pharm Ther 41(5):524–531. https://doi.org/10.1111/jcpt.12430 CrossRefPubMedGoogle Scholar
- 29.Couto JE, Panchal JM, Lal LS et al (2014) Geographic variation in medication adherence in commercial and Medicare part D populations. J Manag Care Spec Pharm 20(8):834–842. https://doi.org/10.18553/jmcp.2014.20.8.834 CrossRefPubMedGoogle Scholar
- 30.Centers for Disease Control and Prevention. National diabetes statistics report. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed 5 Oct 2017
- 31.Theodorou A, Johnson K, Ward M, Szychowski JA (2011) 2010 drug utilization and cost trends for antidiabetic agents. Am J Pharm Benefits 3:54–61Google Scholar
- 32.Hampp C, Borders-Hemphill V, Moeny DG, Wysowski DK (2014) Use of antidiabetic drugs in the U.S., 2003–2012. Diabetes Care 37(5):1367–1374. https://doi.org/10.2337/dc13-289 CrossRefPubMedGoogle Scholar
- 33.Schneider AL, Pankow JS, Heiss G, Selvin E (2012) Validity and reliability of self-reported diabetes in the atherosclerosis risk in communities study. Am J Epidemiol 176(8):738–743. https://doi.org/10.1093/aje/kws156 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Chow EA, Foster H, Gonzalez V, McIver L (2012) The disparate impact of diabetes on racial/ethnic minority populations. Clin Diabetes 30(3):130–133. https://doi.org/10.2337/diaclin.30.3.130 CrossRefGoogle Scholar