Miller, D. C. et al. Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men. Cancer Res. 63, 3486-3489
Department of Urology, University of Michigan, Medical School, Ann Arbor, Michigan 48109-0946, USA. Cancer Research
(Impact Factor: 9.33).
Both rare germ-line mutations and common sequence variants of the macrophage scavenger receptor 1 (MSR1) gene have recently been implicated as potential prostate cancer susceptibility factors. However, existing studies are limited by the referral-based nature of samples and a paucity of African-American participants. In this context, we evaluated the association of germ-line mutations and common MSR1 sequence variants with prostate cancer risk in a case control study of a community-based sample of 134 African-American men with prostate cancer and 340 unaffected controls. In our sample, the rare Asp174Tyr missense change was identified nearly twice as frequently in men with prostate cancer (6.8%) compared with unaffected controls (3.6%; P = 0.14). Moreover, significantly different allele frequencies between cases and controls were observed for one of the sequence variants, IVS5-59 (P = 0.02). Taken together, our results provide some additional support for the hypothesis that selected, rare MSR1 mutations are associated with increased prostate cancer susceptibility among African-American men.
Available from: Wolf H Rogowski
- "The difference in results is likely to be because the PIVOT cohort represented a population with less advanced disease . However the PIVOT sample also included a large number of African Americans (>30%) who have been shown to suffer from an increased risk of developing and dying from PC [41,42]. In order to avoid country specific bias, we chose to use the SPCG data, which represent the European population more realistically. "
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ABSTRACT: There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer.
A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically.
With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of [euro sign]6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of [euro sign]96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS, utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds.
AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients' valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences.
Available from: umu.diva-portal.org
- "In a follow-up study of 301 non- HPC cases and 250 controls, by the same group, five common variants within MSR1 were found, with statistically significant differences in allele and haplotype frequencies (Xu et al., 2003). A number of other independent studies have evaluated the association between prostate cancer and the MSR1 gene, and the generated data have created doubt concerning the role of MSR1 sequence variants in prostate cancer susceptibility (Miller et al., 2003; Seppälä et al., 2003; Wang et al., 2003). RNASEL RNASEL is a constitutively expressed latent endoribonuclease that mediates the antiviral and proapoptotic activities of the interferoninducible 2-5A system. "
Available from: uni-ulm.de
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ABSTRACT: Familial history is one of the strongest risks factor for prostate cancer. One of the prostate cancer candidate genes is the CYP17 gene. A thymidine (T) to cytosine (C) transition (designated A2 variant) in the promoter region of the CYP17 gene has been used in several studies in order to determine a possible association with the prostate cancer risk. A recent meta-analysis found no effect of the CYP17 polymorphism for the sporadic prostate cancer. The question still remained unresolved for familial cases. In order to evaluate the role of the CYP17 A2 allele in familial aggregation of prostate cancer we performed an association study. In our study we realized a slight difference of CYP17 genotypes between sporadic cases and controls, but this unequal distribution was not significant. Our results showed no evidence that the CYP17 genotype might predispose for a familial aggregation of prostate cancer. Our results do not suggest a role of CYP17 as a high-risk susceptibility gene for familial prostate cancer nor as a modifier for the disease risk. Rare germline mutations of the macrophage scavenger receptor 1 (MSR1) gene were reported to be associated with prostate cancer risk in families with hereditary prostate cancer (HPC) and in probands with non-HPC. For the purpose of our study 6 length polymorphisms that span approximately 70kb of the MSR1 gene were used. One of the markers (IVS6 marker) was not in the HWE, so it was excluded from the further analysis. The results gained from analysing the five length polymorphisms did not lead to overall significant results concerning the allele and haplotype frequency distribution between the cases and controls. Some allelic transmission imbalance was seen in the INDEL1 marker when families were analysed with family-based association approach. Taken together our results do not support MSR1 as a high-risk gene for prostate cancer.
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