Abstract C64: SNPs in genes of the glucose-metabolism pathway and prostate cancer: Interplay with metformin

Abstract

Abstract Background: Energy metabolism is important for cancer progression. Energy-producing mitochondria also regulate cell growth and survival. Type II diabetes affects systemic energy metabolism, while both diabetes and antidiabetic treatment likely affect prostate cancer. We studied whether SNPs in genes of the energy-metabolism pathways associate with prostate cancer risk and prognosis, and whether the associations are modified by antidiabetic treatment. Materials and methods: As part of an international PRACTICAL Consortium, 397 SNPs were genotyped on Illumina's custom array (iCOGS) among 3,719 participants of the Finnish Prostate Cancer Screening Trial and 1,528 hospital-based cases. The study population was linked to Finnish national prescription database for information on medication use. After correction for multiple testing using adaptive permutation, SNPs showing an association with prostate cancer incidence or mortality at p < 5 x 10-3 significance level were further explored in multivariable-adjusted Cox regression analyses. Analyses on prostate cancer risk and mortality were adjusted for age and screening trial arm. Analyses on prostate cancer case-fatality were additionally adjusted for tumor stage and grade at diagnosis. Results: After permutation, a total of 30 and 10 SNPs were associated with prostate cancer risk or mortality, respectively. Of these, SNPs in genes PDK1, PGM1 and ENO1 showed consistent associations with prostate cancer risk, disease grade/stage and prostate cancer mortality/case fatality in both study cohorts. The associations with prostate cancer were stronger among antidiabetic drug users in general, although the interaction terms were not significant. Higher cumulative amount of metformin use attenuated the risk increase among antidiabetic drug users. Conclusions: Polymorphisms in genes of the energy-metabolism pathways associate with prostate cancer risk, disease severity and prognosis. This association may be modified by diabetes and antidiabetic drug usage. If validated in further studies, these polymorphisms could be used in risk stratification of prostate cancer patients. Citation Format: Teemu J. Murtola, Tiina Wahlfors, Teuvo LJ Tammela, Liisa Mååttånen, Johanna Schleutker. SNPs in genes of the glucose-metabolism pathway and prostate cancer: Interplay with metformin. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C64.