A nested case-control study of plasma microseminoprotein-beta and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition

Karl SMITH BYRNE, University of Oxford, United Kingdom
SMITH BYRNE K. 1 , KEY T. 1 , APPLEBY P. 1 , LILJA H. 2,3,4 , TRAVIS R. 1

1 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
2 Departments of Laboratory Medicine, Medicine (Genitourinary Oncology), and Surgery (Urology), Memorial Sloan Kettering Cancer Center, New York, NY, USA
3 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
4 Department of Translational Medicine, Lund University, Malmö, Sweden

Purpose
Genome wide association studies have identified a common variant in the promoter region of the MSMB gene, rs10993994, as a risk factor for prostate cancer. MSMB encodes microseminoprotein-beta (MSP), a protein secreted by the prostate epithelial cells into the seminal fluid. There is uncertainty, however, about the role of MSP in the development of prostate cancer.

Methods
A nested case-control study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1,871 cases and 1,871 matched controls to investigate the association of circulating MSP and rs10993994 genotype with prostate cancer risk. Odds ratios (ORs) for prostate cancer by fourths of blood plasma MSP concentration were estimated by conditional logistic regression and MSP association with prostate cancer by rs10993994 genotype was calculated from hierarchical Bayesian logistic regression.

Results
Plasma concentration of MSP was 67% higher for CC genotype when compared to the TT genotype. In a minimally adjusted model, MSP concentration was not significantly associated with prostate cancer risk (OR in the highest versus the lowest fourth = 1.01, 95% CI 0.84-1.22, Ptrend = 0.7). However, after adjusting for prostate-specific antigen (PSA) concentration, higher MSP concentration was associated with a reduced risk of prostate cancer (OR = 0.69, 95% CI 0.54-0.89, Ptrend = 0.004). No heterogeneity in this association was observed by time to diagnosis or tumour characteristics. For CC and CT genotypes, increase in MSP concentrations was associated with a reduced risk of prostate cancer (CC - OR = 0.42, 95% CrI 0.19-0.78; CT - OR = 0.44, 95% CrI 0.23-0.75), while no clear association was observed for TT (OR = 0.71 CrI 0.36-1.61).

Conclusions
The current study shows a significant inverse association of circulating MSP concentration with prostate cancer risk, but only after adjustment for total PSA concentration.