Influence of IGFBP3 Gene Polymorphisms on IGFBP3 Serum Levels and the Risk of Prostate Cancer in Low-risk Korean Men

OBJECTIVES To understand the relationship between the -202 A/C single-nucleotide polymorphism (SNP) of the insulin-like growth factor-binding protein 3 (IGFBP3) gene, IGFBP3 serum levels, and risk of prostate cancer (PCa) in a Korean population, as a potential reason for the lower incidence of PCa in the Korean population. METHODS The IGFBP3 levels were measured and the -202 A/C SNP of the IGFBP3 gene was typed for 225 PCa cases and the same number of matched controls. Linear regression analysis and unconditional logistic regression analysis were used to test for the associations between the genotypes and the circulating IGFBP3 levels and the risk of PCa, respectively. To adjust for the potential bias introduced by the hospital cohort, the result of the genotyping was compared with that of 683 community-indwelling healthy men. RESULTS Significantly lower plasma levels of IGFBP3 were noted in the PCa cases. Lower IGFBP3 plasma levels were associated with an increased number of C alleles (P < .001). Compared with the PCa cases, a lower frequency of the C allele was found in the hospital and community controls (P < .05). Compared with AA genotype, logistic regression analysis revealed an increased risk of PCa in subjects who were CC genotype (odds ratio: 2.39, 95% confidence interval: 1.05-5.48). Larger odds (odds ratio: 3.37, 95% confidence interval: 1.35-8.43) for PCa were associated with CC genotype when the analysis was confined to those who had high-risk PCa. CONCLUSIONS The results supported the protective role of -202 A/C SNP of the IGFBP3 gene against PCa in Korean men.Raimondi S, 2009, CARCINOGENESIS, V30, P1170, DOI 10.1093/carcin/bgp103Hernandez W, 2007, CARCINOGENESIS, V28, P2154, DOI 10.1093/carcin/bgm190Liu B, 2007, ONCOGENE, V26, P1811, DOI 10.1038/sj.onc.1209977LEE J, 2007, CANC CONTROL, V14, P78Qin LQ, 2007, ASIA PAC J CLIN NUTR, V16, P467Chen C, 2006, CANCER EPIDEM BIOMAR, V15, P2461, DOI 10.1158/1055-9965.EPI-06-0541Severi G, 2006, CANCER EPIDEM BIOMAR, V15, P1137, DOI 10.1158/1055-9965.EPI-05-0823Silha JV, 2006, ENDOCRINOLOGY, V147, P2112, DOI 10.1210/en.2005-1270Moon JW, 2006, INT J CANCER, V118, P353, DOI 10.1002/ijc.21339Li L, 2005, CANCER EPIDEM BIOMAR, V14, P2462, DOI 10.1158/1055-9965.EPI-05-0531Schildkraut JM, 2005, CANCER EPIDEM BIOMAR, V14, P403Chen C, 2005, CANCER, V103, P76, DOI 10.1002/cncr.20727DeLellis K, 2004, CANCER EPIDEM BIOMAR, V13, P1444Peng LH, 2004, MOL ENDOCRINOL, V18, P1109, DOI 10.1210/me.2003-0344Wang LZ, 2003, CANCER RES, V63, P4407Gunnell D, 2003, BRIT J CANCER, V88, P1682, DOI 10.1038/sj.bjc.6600946Chokkalingam AP, 2001, CANCER EPIDEM BIOMAR, V10, P421Deal C, 2001, J CLIN ENDOCR METAB, V86, P1274Verhage BAJ, 2001, UROLOGY, V57, P97BAXTER RC, 2001, MOL PATHOL, V54, P145Stattin P, 2000, J NATL CANCER I, V92, P1910Harman SM, 2000, J CLIN ENDOCR METAB, V85, P4258Platz EA, 1999, CANCER EPIDEM BIOMAR, V8, P1107Tricoli JV, 1999, UROLOGY, V54, P178Parkin DM, 1999, INT J CANCER, V80, P827STANFORD JL, 1999, NIH PUBD`Amico AV, 1998, JAMA-J AM MED ASSOC, V280, P969Wolk A, 1998, J NATL CANCER I, V90, P911Schaid DJ, 1998, AM J HUM GENET, V62, P1425Chan JM, 1998, SCIENCE, V279, P563Page WF, 1997, PROSTATE, V33, P240Harrela M, 1996, J CLIN INVEST, V98, P2612KAO PC, 1994, J CLIN ENDOCR METAB, V78, P310SHIMIZU H, 1991, BRIT J CANCER, V63, P963