Abstract 2683: Biomarkers of glucose homeostasis and inflammation and risk of prostate cancer: A case-cohort study

Abstract

Abstract Background: Type 2 diabetes (T2DM) is associated with a lower risk of prostate cancer especially low-grade and localized prostate cancer. The association with aggressive prostate cancer is inconclusive. Few studies have directly examined the associations of diabetes biomarkers with prostate cancer risk. Methods: Among a cohort of 13,994 men who were on average 70.2 years (SD=5.5) and cancer free at blood draw between 1998 and 2001, 1,206 developed non-aggressive prostate cancer and 313 developed aggressive prostate cancer (AJCC stage 3-4 or Gleason score 8-10) during follow-up through June 2013. We conducted a case-cohort study including a random sub-cohort of 1,303 men, 391 non-aggressive cases and 313 aggressive cases to examine circulating hemoglobin A1c (HbA1c), c-peptide, and C-reactive protein (CRP) in relation to prostate cancer risk. Results: HbA1c, a biomarker of hyperglycemia, was inversely associated with non-aggressive prostate cancer after adjusting for age, race, family history of prostate cancer, prostate-specific antigen screening, smoking, alcohol intake, physical activity, and total energy intake (relative risk (RR) per unit increase: 0.89, 95% confidence interval (CI): 0.79-1.00, P=0.04). Further adjustment for body mass index (BMI) attenuated the association. In contrast, HbA1c was associated with a higher risk of aggressive prostate cancer after adjusting for the covariates including BMI (RR per unit increase: 1.11, 95% CI: 0.98-1.25, P=0.11). In an analysis combining self-reported T2DM and HbA1c, men with T2DM and poor blood glucose control (HbA1c ≥6.5%) had a lower risk of developing non-aggressive prostate cancer (RR: 0.53, 95% CI: 0.30-0.95) than men without T2DM and good blood glucose control (HbA1c <6.5%). After excluding men with self-reported T2DM, HbA1c was statistically significantly positively associated with risk of aggressive prostate cancer (RR per unit increase: 1.25, 95% CI: 1.04-1.51, P=0.02) but was not associated with non-aggressive prostate cancer. C-peptide and CRP were not associated with risk of either aggressive or non-aggressive prostate cancer.Conclusions: The present study suggests that men with hyperglycemia may have a lower risk of developing non-aggressive but a higher risk of developing aggressive prostate cancer. Further studies are needed to examine the role of hyperglycemia in the etiology of aggressive prostate cancer and in prostate cancer progression. Citation Format: Ying Wang, Peter T. Campbell, Victoria L. Stevens, Christina C. Newton, Eric J. Jacobs, Michael Pollak, Susan M. Gapstur. Biomarkers of glucose homeostasis and inflammation and risk of prostate cancer: A case-cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2683.