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Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis.

ABSTRACT: BACKGROUND: The insulin-like growth factor-1 (IGF-1) plays an important role in growth of prostate cancer (PCa) cells and facilitating the development and progression of PCa. This study aimed to evaluate the association of polymorphisms in three linkage disequilibrium (LD) blocks of the IGF-1 on the survival of metastatic PCa patients. METHODS: A total of 215 patients with bone metastases at initial presentation were included in this study. The cytosine-adenine (CA) repeat polymorphism and rs12423791 were selected as representative polymorphisms in the LD blocks 1 and 2, respectively. Haplotype in the LD block 3 was analyzed using two tag single nucleotide polymorphisms (SNPs), rs6220 and rs7136446. Cancer-specific survival rate was estimated from the Kaplan-Meier curve, and the survival data were compared using the log-rank test. RESULTS: Cancer-specific survival was significantly associated with the CA repeat polymorphism, rs12423791, and rs6220 (P = 0.013, 0.014, and 0.014, respectively). Although rs7136446 had no significant association with survival, the haplotype in the LD block 3 was significantly associated with cancer-specific survival (P = 0.0003). When the sum of the risk genetic factors in each LD block (19-repeat allele, C allele of rs12423791, or C-T haplotype) was considered, patients with all the risk factors had significantly shorter cancer specific-survival than those with 0-2 risk factors (P = 0.0003). CONCLUSIONS: Polymorphisms in the IGF-1, especially a haplotype in the LD block 3, are assumed to be genetic markers predicting the outcome of metastatic PCa.

SUBMITTER: Tsuchiya N

PROVIDER: S-EPMC3622563 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis.

Tsuchiya Norihiko N Narita Shintaro S Inoue Takamitsu T Saito Mitsuru M Numakura Kazuyuki K Huang Mingguo M Hatakeyama Shingo S Satoh Shigeru S Saito Seiichi S Ohyama Chikara C Arai Yoichi Y Ogawa Osamu O Habuchi Tomonori T

BMC cancer 20130325

<h4>Background</h4>The insulin-like growth factor-1 (IGF-1) plays an important role in growth of prostate cancer (PCa) cells and facilitating the development and progression of PCa. This study aimed to evaluate the association of polymorphisms in three linkage disequilibrium (LD) blocks of the IGF-1 on the survival of metastatic PCa patients.<h4>Methods</h4>A total of 215 patients with bone metastases at initial presentation were included in this study. The cytosine-adenine (CA) repeat polymorph ...[more]

PMID: 23530598

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Project description:What is already known about this subjectRecent studies on pharmacogenetics of warfarin have implicated apolipoprotein E (APOE) polymorphisms to influence the vitamin K dependent coagulation cascade and hence the efficacy of warfarin. Studies among Caucasian and African Americans showed a significant but conflicting role of apolipoprotein E (APOE) isoforms in warfarin pharmacogenetics. The contribution of APOE isoforms in influencing variations in warfarin requirements in Asian subjects remains to be investigated.What this study addsThis is the first report of a population study in Asians exploring the role of isoforms encoded by three APOE alleles (epsilon 2, epsilon 3, epsilon 4) in influencing warfarin dose requirements. The present study showed that the APOE epsilon 3/epsilon 3 isoform is the predominant genotype in the Asian population. The study also showed that APOE isoforms may not be important in affecting warfarin pharmacodynamics in Asian patients. It also suggested that the impact of different APOE isoforms depended on the frequency of APOE genotypes in the population, in particular the epsilon 4 allele containing genotypes.AimsTo investigate the influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients.MethodsA total of 174 Asian patients (Chinese, n = 96; Malays, n = 50; Indians, n = 28) who had stable daily warfarin doses for at least 1 month were recruited. Following genomic DNA extraction from venous blood, pharmacogenetic analysis of APOE and VKORC1 genes was done by DNA sequencing.ResultsThe majority of the Asian patients (78%) harboured the APOE epsilon 3/epsilon 3 genotype. Different APOE genotypes were found not to have any significant influence on mean daily warfarin dose requirements. Warfarin dose requirements in the pooled Asian patients homozygous for the VKORC1 H1 haplotype were significantly lower compared with patients homozygous for the H7 haplotype (H1-H1 vs. H7-H7: 2.79 +/- 1.06 mg day(-1)vs. 5.45 +/- 2.3 mg day(-1), P < 0.001).ConclusionsThe present study suggests that APOE variants have minimal impact on warfarin dose requirements in Asian patients, probably due to the low frequency of epsilon 4 allele containing genotypes.

Dataset Information

Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis.

Publications

Insulin-like growth factor-1 genotypes and haplotypes influence the survival of prostate cancer patients with bone metastasis at initial diagnosis.

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