Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 5057
© 2008 American Society of Clinical Oncology

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Abstract

Effect of a germline polymorphism in the manganese superoxide dismutase (MnSOD) gene on the association of clinically aggressive prostate cancer with plasma selenium levels

Dana-Farber Cancer Institute, Boston, MA; University of California San Francisco Cancer Center, San Francisco, CA

5057

Introduction: We previously identified modified risk of prostate cancer by antioxidant levels and polymorphism in the MnSOD gene (rs4880) (Cancer Res 2005;65:2498). We further explore interaction between this polymorphism, plasma selenium levels and clinically aggressive prostate cancer. Methods: 778 patients with localized prostate cancer and pretreatment plasma was identified from a single institution. MnSOD polymorphism (rs4880) was genotyped in 764 subjects. Plasma selenium levels were measured in 499. Aggressive disease was stage T2b, PSA>10ng/mL or Gleason7. Relative risk (RR) and 95% CI were calculated. Results: A total of 489 patients had clinical, selenium and genotype data. Median age was 62 years (range 43–86). Median PSA was 6 ng/mL (range 0.7–575.8). Biopsy Gleason score 7 and T stage T2b were noted in 35.7% and 2.4%, respectively. 43% of patients had aggressive disease at diagnosis. There was no overall association of aggressiveness with MnSOD genotype or plasma selenium levels (p>0.05). However, the rs4880 polymorphism significantly modified the relationship between disease risk with selenium levels (P-value for interaction=0.02; Table). Among men with genotype AA, higher selenium levels (quintile 5 vs1) were associated with lower risk for aggressive prostate cancer (RR=0.6, 95% CI: 0.321.12, P-trend=0.05). By contrast, there was a positive correlation between higher selenium levels and aggressive disease in men with VV/AV genotype (P-value for trend < 0.05). Conclusions: The association between aggressive prostate cancer and pretreatment selenium levels was modified by a polymorphism in MnSOD. Men with genotype AA were less likely to develop aggressive prostate cancer with higher selenium levels. Interestingly, a reverse relationship was observed in men with VV/AV genotypes suggesting that for them, higher selenium levels may be deleterious.

No significant financial relationships to disclose.

Abstract presentation from the 2008 ASCO Annual Meeting