TY - JOUR
T1 - Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer
AU - Abe, Miyako
AU - Xie, Wanling
AU - Regan, Meredith M.
AU - King, Irena B.
AU - Stampfer, Meir J.
AU - Kantoff, Philip W.
AU - Oh, William K.
AU - Chan, June M.
PY - 2011/1
Y1 - 2011/1
N2 - OBJECTIVE: To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer. PATIENTS AND METHODS We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator-activated receptor γ coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and 'X-ray repair complementing defective repair in Chinese hamster cell 1' (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate-specific antigen (PSA) level (213 aggressive cases). RESULTS Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70-0.99; and rs4816407, 1.27, 1.02-1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 μg/L, P= 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330). CONCLUSION While this study was cross-sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer.
AB - OBJECTIVE: To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer. PATIENTS AND METHODS We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator-activated receptor γ coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and 'X-ray repair complementing defective repair in Chinese hamster cell 1' (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate-specific antigen (PSA) level (213 aggressive cases). RESULTS Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70-0.99; and rs4816407, 1.27, 1.02-1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 μg/L, P= 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330). CONCLUSION While this study was cross-sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer.
KW - aggressive prostate cancer
KW - glutathione peroxidase
KW - plasma selenium
KW - single nucleotide polymorphisms
KW - superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=78650663377&partnerID=8YFLogxK
U2 - 10.1111/j.1464-410X.2010.09344.x
DO - 10.1111/j.1464-410X.2010.09344.x
M3 - Article
C2 - 20477822
AN - SCOPUS:78650663377
SN - 1464-4096
VL - 107
SP - 126
EP - 134
JO - BJU International
JF - BJU International
IS - 1
ER -