Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.     

WHOLE GENOME AMPLIFICATION AND MOLECULAR GENETIC ANALYSIS OF DNA FROM PARAFFIN-EMBEDDED PROSTATE ADENOCARCINOMA TUMOR TISSUE

PURPOSE: Often tissues obtained from prostate adenocarcinoma tumors embedded in paraffin are heterogeneous in cell type and must be carefully microdissected to acquire tissue fragments that provide homogeneous aliquots of tumor clones. Such tissue fragments rarely contain sufficient DNA to perform genomic characterization needed as an early step in localizing relevant oncogenes or tumor suppressor genes. We report that PCR using a degenerate oligonucleotide primer (DOP-PCR) can be applied to DNA samples from microdissected paraffin-embedded prostate adenocarcinomas, and this provides sufficient product for fluorescent allelic imbalance measurements or comparative genomic hybridization (CGH). MATERIALS AND METHODS: Samples were selected to be representative of those routinely obtained during prostatectomies, based on typical tumor stages (T2 and T3) and Gleason grades (range 3 +3 to 4 +5). For DNA analysis without prior DOP-PCR, only large tumors were selected to be sectioned. More than 50 specimens were analyzed. Close comparison of data obtained from analysis of DOP-PCR with those from non-DOP DNA was obtained on a subset 8 samples. To compare the allelic balance of DOP-PCR amplified DNA with that measured for non-DOP DNA, we analyzed allelic ratios on DNA from 5 different tissue samples processed by both microdissection and conventional sectioning. RESULTS: Systematic comparison of allelic imbalance results shows close similarity between DOP-PCR amplified product and non-DOP DNA, indicating that PCR product is a valid representation of the tumor genome. In addition, the difference between allelic balance and imbalance is more distinctive when microdissection followed by DOP-PCR is performed. Performing CGH on products of DOP-PCR also shows distinctive regional copy number alterations in DNA from microdissected tumor tissue. CONCLUSION: Either of these procedures allows distinction between benign and malignant genomes, and also allows independent analysis of genomic alterations in different portions of tumors. They also may be applied clinically for genomic characterization of small foci that frequently appear in prostates of elderly men who are showing no obvious pathological symptoms of adenocarcinoma.     

The clinical phenotype of hereditary versus sporadic prostate cancer: HPC definition revisited

BACKGROUND

The definition of hereditary prostate cancer (HPC) is based on family history and age at onset. Intuitively, HPC is a serious subtype of prostate cancer but there are only limited data on the clinical phenotype of HPC. Here, we aimed to compare the prognosis of HPC to the sporadic form of prostate cancer (SPC).

METHODS

HPC patients were identified through a national registry of HPC families in the Netherlands, selecting patients diagnosed from the year 2000 onward (n = 324). SPC patients were identified from the Netherlands Cancer Registry (NCR) between 2003 and 2006 for a population‐based study into the genetic susceptibility of PC (n = 1,664). Detailed clinical data were collected by NCR‐registrars, using a standardized registration form. Follow‐up extended up to the end of 2013. Differences between the groups were evaluated by cross‐tabulations and tested for statistical significance while accounting for familial dependency of observations by GEE. Differences in progression‐free and overall survival were evaluated using χ² testing with GEE in a proportional‐hazards model.

RESULTS

HPC patients were on average 3 years younger at diagnosis, had lower PSA values, lower Gleason scores, and more often locally confined disease. Of the HPC patients, 35% had high‐risk disease (NICE‐criteria) versus 51% of the SPC patients. HPC patients were less often treated with active surveillance. Kaplan–Meier 5‐year progression‐free survival after radical prostatectomy was comparable for HPC (78%) and SPC (74%; P = 0.30). The 5‐year overall survival was 85% (95%CI 81–89%) for HPC versus 80% (95%CI 78–82%) for SPC (P = 0.03).

CONCLUSIONS

HPC has a favorable clinical phenotype but patients more often underwent radical treatment. The major limitation of HPC is the absence of a genetics‐based definition of HPC, which may lead to over‐diagnosis of PC in men with a family history of prostate cancer. The HPC definition should, therefore, be re‐evaluated, aiming at a reduction of over‐diagnosis and overtreatment among men with multiple relatives diagnosed with PC. Prostate 76:897–904, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.     

Allelic loss of the retinoblastoma gene in primary human prostatic adenocarcinomas

Inactivation of the retinoblastoma (Rb) gene has been implicated in the genesis and progression of a number of tumor types, including prostatic adenocarcinomas. We have analyzed a series of 46 surgically-resected human prostatic adenocarcinomas for allelic loss of the Rb gene with PCR amplification of a highly polymorphic region of the gene. 41 of 46 tumors (89%) were informative and 11 of these (27%) had lost one Rb allele. The relative frequency of this occurrence suggests that inactivation of the retinoblastoma gene may be an important event in prostate carcinogenesis.     

Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer

BACKGROUND: Allelic losses on chromosome arms 2q, 3p, 5q, 6q, 7q, 8p, 9p, 10p, 10q, 11p, 11q, 12p, 13q, 16q, 17p, 17q, 18q, and 21q are reportedly associated with progression and/or initiation of prostate cancer. In the present study, we performed a polymerase chain reaction (PCR) analysis of polymorphic microsatellite loci on the human chromosomes 7 and 12p13-12 in prostate cancer tissue to investigate the extent of involvement of these regions, which may contain putative tumor suppressor genes. METHODS: Tissue samples were obtained at autopsy from 17 men who died of hormone-refractory prostate cancer at Chiba University, Japan, and affiliated hospitals between June of 1992 and June of 1995. DNA from normal tumor or metastatic tissue was used as the template for PCR amplification of a set of 16 polymorphic microsatellite loci on human chromosome 7 and 6 loci on the human chromosome region 12p13-12. RESULTS: The frequencies of cases with loss of heterozygosity (LOH) at 7q31.1 were 8% in primary tumor tissue and 11% in metastatic tissue. The frequencies of cases with LOH at 12p13-12 were 12% in primary tumor tissue and 25% in metastatic tumor tissue. CONCLUSIONS: In the present study, the frequencies of LOH at 7q31.1 were lower than in Western patients, suggesting that LOH in this region is not related to progression of prostate cancer in Japanese patients. The frequency of LOH at 12p13-12 was similar to that reported in Western countries, indicating that 12p13-12 may contain a tumor suppressor gene of prostate cancer.     

Loss of heterozygosity on chromosome 2 in Japanese patients with prostate cancer

BACKGROUND: Loss of heterozygosity (LOH) on chromosome 2 is thought to occur only occasionally in prostate cancer (PCa), but allelic losses in this region are frequent in other types of human cancer, such as lung, thyroid, head and neck, and cervix. Here, we show a high-resolution deletion map of markers on chromosome 2 in Japanese patients with PCa. METHODS: Tissue samples were obtained from 66 patients with PCa. DNA from normal, tumor, or metastatic tissue was used as the template for polymerase chain reaction amplification for LOH using 24 microsatellite markers on human chromosome 2. RESULTS: Nineteen of the 66 cases (29%) showed LOH for at least one locus on chromosome 2. LOH on 2p was observed more frequently in cancer death cases than in organ confined and regional diseases (P < 0.001). Paired DNAs were available from both primary and metastatic tumors in the eight cases of cancer death; among those pairs, we detected LOH on 2p in four primary tumors, and in all metastatic foci (P < 0.05). Detailed deletion mapping in these tumors identified four distinct commonly deleted regions on 2p 16.3, 2p 12-cent, 2q 21.3, and 2q 23.1-2q 32.1. CONCLUSIONS: These results suggest that inactivation of putative tumor suppressor genes on chromosome 2 that may play an important role in the progression of Japanese patients with PCa.     

Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer

BACKGROUND: The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS: Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS: Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS: Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.     

Retinoblastoma gene mutations in primary human prostate cancer

Structural alterations in the entire coding regions (exons 1 to 27) of the retinoblastoma (RB) gene in primary human prostate cancers were investigated, using polymerase chain reaction and single strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, four (16.4%) were found to have RB alterations. DNA sequencing of the PCR products revealed point mutations resulting in single amino-acid substitutions of exons 6 and 19 in two cases, and base deletions of exons 8 and 17 in two cases. Two of four cases with RB mutations were moderately differentiated localized tumors and other two with RB mutations were poorly differentiated tumors with metastases. Our results suggest that RB gene mutation is involved in progression steps of prostate carcinogenesis. © 1995 Wiley-Liss, Inc.     

前列腺癌及高级别前列腺上皮内肿瘤8号染色体等位基因杂合性缺失分析

目的 :分析原发性前列腺癌及高级别前列腺上皮内肿瘤 (PIN) 8号染色体等位基因杂合性缺失 (LOH)并探讨其意义。　方法 :经显微切割获取前列腺癌及PIN各 10个样本DNA ,采用PCR及微卫星多态性技术 ,对 8号染色体上的 14个微卫星位点LOH进行检测。　结果 :10个原发性前列腺癌样本在 8号染色体有不同LOH的频率 ,8p 2 3.1 p2 3.2及 8p2 1 p2 2为两个高频LOH区。 10个高级别PIN样本检测 8号染色体 14个微卫星位点 ,有 5个样本至少有一个位点检测到LOH。　结论 :前列腺癌中存在 8号染色体的高频LOH区 ,分别位于 8p 2 3.1 p 2 3.2 ,8p2 1 p2 2区 ,高级别PIN出现LOH的位点与前列腺癌相同 ,位于 8p 2 3.1 p 2 3.2及 8p2 1 p2 2区的肿瘤抑制基因可能与前列腺癌的发生发展有关     

Population-based risk assessment for other cancers in relatives of hereditary prostate cancer (HPC) cases

BACKGROUND: To identify associations of other cancers with hereditary prostate cancer (HPC) we estimated relative risks (RRs) of 36 different cancers in relatives of prostate cancer cases in the Utah Population Data Base (UPDB), which combines genealogical and cancer data for Utah. METHODS: We utilized known genetic relationships between prostate cancer cases and their relatives with cancer, combined with age- and sex-specific cancer rates calculated internally from the UPDB, to estimate RRs for cancer in relatives of prostate cancer cases. RESULTS: Multiple other cancers were observed in excess in both first- and second-degree relatives of HPC cases including colon cancer, non-Hodgkins lymphoma, multiple myeloma, rectal cancer, cancer of the gallbladder, and melanoma (skin). CONCLUSIONS: This analysis supports the existence of heritable prostate cancer syndromes that include other cancers. We hypothesize that the study of homogeneous pedigrees co-segregating prostate cancer and another cancer could allow more straightforward localization and identification of the gene(s) responsible.     

Analysis on chromosome 8 heterozygosity loss in humanprostate carcinoma and high grade prostaticintraepithelial neoplasia

Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. The chromosome 8 heterozygosity loss was detected by PCR based micro-satellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade prostatic intraepithelial neoplasia. Results: There were different frequencies of chromosome 8 heterozygosity loss in 10 samples of prostate carcinoma. 8p23.1-p23.2 and p21-p22 were two high frequency heterozygosity loss regions. Chromosome 8 heterozygosity loss was detected in 3 samples of high grade prostatic intraepithelial neoplasia. Conclusion: There were high frequency heterozygosity loss regions on chromosome 8 of prostate carcinoma, located at 8p23.1-p23.2 and p21-p22. The high grade prostatic intraepithelial neoplasia and prostate carcinoma share     

Counting alleles in single lesions of prostate tumors from ethnically diverse patients

BACKGROUND: The presence of racial disparities in incidence and mortality rates are well-documented for prostate cancer. Nevertheless, it is unclear whether such disparities are due to genetic alterations that are involved in prostate cancer initiation. Here, we evaluated chromosome 8p allelic loss in a racially diverse cohort. METHODS: Laser-capture microdissection was used to isolate tumors cells from individual lesions in 153 prostate cancer patients, and 8p allelic status was determined by "counting alleles." Statistical analyses examined the association between pathologic predictors and biochemical recurrence. RESULTS AND CONCLUSIONS: Thirty percent of prostate lesions were missing an 8p allele at tumor initiation, while 51% of lesions lost an 8p allele during tumor progression. Biochemical recurrence after radical prostatectomy could be reliably predicted by surgical margin status only in lesions with extensive 8p allelic loss. There was, however, no racial disparity in 8p allelic loss at tumor initiation or during tumor progression, suggesting that the molecular event involved was similar between Caucasians and Africa Americans (CA and AA). Nonetheless, racial differences were present in values of prognostic factors for recurrence. Gleason score was the most important predictor of recurrence (HR=3.1, 95% CI=1.1, 9.2) in AA, while among CA, pathologic stage (HR=3.3, 95% CI=1.5, 7.6) and surgical margin (HR=4.7, 95% CI=1.8, 12.6) were the most important. Therefore, racial disparity in prostate cancer may be due to other factors that are involved in prostate cancer development.     

Inactivation of the NF2 tumor suppressor protein merlin in DU145 prostate cancer cells

BACKGROUND: The neurofibromatosis 2 (NF2) tumor suppressor gene product merlin is an important regulator of contact-dependent cell proliferation. Phosphorylation of merlin at serine 518 (Ser518) by the Rac effector p21-activated kinase (PAK) inactivates merlin's growth suppressing function, and is regulated by cell-culture conditions, including cell density, cell/substrate attachment, and growth factor availability. We examined the regulation of merlin expression and merlin phosphorylation in prostate cancer cells. METHODS: Phosphorylation of merlin in five prostate cancer cell lines (LNCaP, DU145, PC3, 22RV1, and LAPC-4) was examined by Western blotting using anti-phospho-merlin (Ser518) antibody. The activity of PAK, an upstream regulator of merlin phosphorylation, was measured by Western blotting using phospho-PAK (Ser141) antibody. The effects of various cell-culture conditions on the phosphorylation levels of merlin and PAK were analyzed. RESULTS: Both merlin expression and phosphorylation were low in LNCaP, PC3, 22RV1, and LAPC-4 prostate cancer cells. In DU145 cells, total and phosphorylated merlin were abundant, but phosphorylation was not inhibited by high cell density, serum withdrawal, the addition of hyaluronic acid or inhibition of CD44 expression, all of which are reported to inhibit merlin phosphorylation in non-neoplastic cells. PAK activation was elevated in DU145 cells and the addition of a PAK-specific inhibitor peptide but not the Rac1-specific inhibitor NSC23766 inhibited both PAK and merlin phosphorylation. CONCLUSIONS: Merlin is inactivated in DU145 prostate cancer cells by PAK-mediated constitutive phosphorylation, identifying a novel mechanism of merlin inactivation in neoplastic cells.     

Suggestive genetic linkage to chromosome 11p11.2-q12.2 in hereditary prostate cancer families with primary kidney cancer

BACKGROUND: The Seattle-based PROGRESS study was started in 1995 to ascertain hereditary prostate cancer (HPC) families for studies of genetic susceptibility. Subsequent studies by several research groups, including our own, suggest that HPC is a genetically heterogeneous disease. To be successful in mapping loci for such a complex disease, one must consider ways of grouping families into subsets that likely share the same genetic origin. Towards that end, we analyzed a genome-wide scan of HPC families with primary kidney cancer. METHODS: An 8.1 cM genome-wide scan including 441 microsatellite markers was analyzed by both parametric and non-parametric linkage approaches in fifteen HPC families with the co-occurrence of kidney cancer. RESULTS: There was no evidence for significant linkage in the initial findings. However, two regions of suggestive linkage were observed at 11q12 and 4q21, with HLOD scores of 2.59 and 2.10, respectively. The primary result on chromosome 11 was strengthened after excluding two families with members who had rare transitional cell carcinoma (TCC). Specifically, we observed a non-parametric Kong and Cox P-value of 0.004 for marker D11S1290 at 11p11.2. The 8 cM region between 11p11.2 and 11q12.2 was refined by the addition of 16 new markers. The subset of HPC families with a median age of diagnosis >65 years demonstrated the strongest evidence for linkage, with an HLOD = 2.50. The P-values associated with non-parametric analysis ranged from 0.004 to 0.05 across five contiguous markers. CONCLUSIONS: Analysis of HPC families with members diagnosed with primary renal cell carcinoma demonstrates suggestive linkage to chromosome 11p11.2-q12.2.     

Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer

BACKGROUND: The genetic basis of susceptibility to prostate cancer (PRCA) remains elusive. Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases. PALB2 is a recently identified breast cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures. This functional relationship made PALB2 a candidate PRCA susceptibility gene. METHODS: We sequenced PALB2 in probands from 95 PRCA families, 77 of which had two or more cases of early onset PRCA (age at diagnosis <55 years), and the remaining 18 had one case of early onset PRCA and five or more total cases of PRCA. RESULTS: Two previously unreported variants, K18R and V925L were identified, neither of which is in a known PALB2 functional domain and both of which are unlikely to be pathogenic. No truncating mutations were identified. CONCLUSIONS: These results indicate that deleterious PALB2 mutations are unlikely to play a significant role in hereditary prostate cancer.     

KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer

BACKGROUNDS: Previous studies mapped a region at the q21 band of chromosome 13 (13q21), which is frequently deleted in various human cancers including prostate cancer, suggesting the existence of a tumor suppressor gene at 13q21. The target gene of deletion in prostate cancer, however, has not been identified at present. METHODS: We examined four non-neoplastic and 18 neoplastic prostatic cell lines or xenografts. Homozygous/hemizygous deletion was detected by assays of duplex PCR and real-time PCR. Expression levels of genes were determined by the methods of RT-PCR, real time PCR, and northern blot analysis. Mutations of KLF5 were detected by the approaches of single strand conformational polymorphism (SSCP) and direct sequencing. For the detection of promoter methylation, Southern blotting of genomic DNA and restriction digestion or SSCP analysis of methylation specific PCR products were used. Finally, an expression plasmid of KLF5 was introduced into prostate cancer cell lines with reduced KLF5 expression to investigate colony formation for cell growth. RESULTS: A 2-Mb region of homozygous deletion at 13q21 was detected in the LUCaP70 xenograft of prostate cancer. This region of deletion was further narrowed to 142 Kb by a hemizygous deletion in the NCI-H660 cell line. KLF5 was identified as the only complete gene in the smallest region of deletion. Quantitative deletion of KLF5 genome occurred in six of the 18 (33%) prostate cancer xenografts/cell lines. Each of the six samples with deletion also showed loss of expression for KLF5, suggesting that hemizygous deletion is one mechanism for loss of KLF5 expression. In total, 16 of the 18 cases (89%) showed loss of KLF5 expression at different degrees. In contrast, mutations and promoter methylations were not detected in any of the samples. Functionally, restoration of KLF5 in DU 145 and 22Rv1 cell lines significantly inhibited their growth in vitro. CONCLUSIONS: Frequent genomic deletion and loss of expression as well as cell growth suppression indicate that KLF5 is a reasonable candidate for the tumor suppressor gene at 13q21 in prostate cancer. Mutation and promoter methylation are not common mechanisms for the inactivation of KLF5 in prostate cancer.     

细胞因子信号传导抑制蛋白-3在前列腺癌中作用的研究进展

细胞因子信号抑制蛋白-3(suppressor of cytokine signaling-3,SOCS-3)是一种很常见的抑制性信号调节蛋白,可参与负反馈调节Janus激酶、转录激活因子(JAK/STAT)及信号转导等多种重要信号通路,从而调控细胞因子、生长因子等对细胞的作用。SOCS-3可通过多种机制调节前列腺癌细胞的迁移及侵袭能力。本文主要就SOCS-3在这一方面的研究进展作一简单综述。     

Analysis of the macrophage scavenger receptor 1 gene in Swedish hereditary and sporadic prostate cancer

BACKGROUND: The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS: DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS: A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5'- or 3'-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P = 0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION: Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology.