title: Macrophage inhibitory cytokine-1 H6D polymorphism, prostate cancer risk, and survival.
abstract: Macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-beta superfamily, is important in regulating inflammation. Inflammation of the prostate has been suggested to favor tumor development. A recent study (JNCI 2004, 96:1248-1254) found marginal evidence of an association between the presence of the mature MIC-1 protein nonsynonymous polymorphism H6D C-to-G (rs1058587) with reduced prostate cancer risk [odds ratio, 0.83; 95% confidence interval (95% CI), 0.69-0.99]. We tested this in a population-based study of 819 cases and 731 controls from Australia and found a similar, yet not significant, odds ratio of 0.85 (95% CI, 0.7-1.04; P = 0.11). We also tested the potential association between the H6D variant and disease-specific survival in 640 cases followed-up for an average of 8.2 years. We found that cases carrying the H6D G allele had an increased risk of death from prostate cancer than cases carrying two copies of the C allele (hazard ratio, 1.72; 95% CI, 1.06-2.78; P = 0.03). Our data suggest that the H6D variant in MIC-1 might play a role in prostate cancer, but it is difficult to explain how a variant can be associated with lower risk of developing prostate cancer but more aggressive growth if cancer develops.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. v.hayes@garvan.org.au
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hayes
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Emma J D
authors.initials: EJ
authors.lastname: Padilla
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D000368:Aged; D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D055436:Growth Differentiation Factor 15; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate
chemical_list: D016207:Cytokines; D004273:DNA, Neoplasm; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15