Association between common sequence variants in the macrophage scavenger receptor 1 gene and the prostate cancer risk in the Japanese population

LB-5

Introduction and Objectives: Prostate cancer (PC) is one of the most common causes of cancer mortality in Western countries and the familial aggregation of PC is well known. In Japan, the incidence rate of PC is low, however, it has been increasing over the past tenyears. We previously conducted a genomewide linkage analysis in 44 nuclear Japanese families affected with PC and concluded that the susceptibilities to PC in our country was thus close to D8S550 on 8p23 and D1S2667 on 1p36. The Macrophage Scavenger Receptor 1 (MSR1) gene exists very close to 8p23 and there have also been some reports of its common sequence variants being associated with PC in Western countries. In the present study, we examined the association between the MSR1 gene and PC risk in the Japanese population.
 Methods: The present study included probands from 132 families with familial PC (FPC), 153 patients with sporadic PC (SPC) and 120 patients with benign prostatic hyperplasia (BPH) serving as control subjects. All study subjects belonged to the Japanese ethnic group. We directly determined the sequences of the PCR products of all 11 exons, exon-intron junctions, and promoter regions and 5’ and 3’ UTRs of MSR1 in the germline DNA. The association of MSR1 genotypes with family history and the clinical features of PC were evaluated by the chi-square test.
 Results: We identified four common sequence variants (PRO3, INDEL1, P275A and INDEL7) as reported previously, and the other 12 SNPs in the samples of PC. The frequency of allele “C” of P275A (61.7% vs 52.9% P = 0.045) was higher in the FPC subjects than in the control subjects. The odds ratio of the genotypes with “CG and CC” of P275A [2.26 (95% CI: 1.20-4.24, P = 0.010)], and deletion “-/+ and -/-” of INDEL7 [1.87 (1.03-3.41, 0.039)] were significantly higher in the FPC subjects than in the control subjects. In addition, the FPC subjects with the age at diagnosis > 60 years showed significantly higher frequencies of allele “A” of P275A than those of the control subjects (62.5% P = 0.049).
 Conclusions: The significant differences in the allele frequencies and genotypes between FPC and the unaffected control subjects observed in this study are therefore considered to support the notion that the MSR1 gene might also play an important role in the susceptibility to PC in the Japanese population.