RNASEL Asp541Glu and Arg462Gln polymorphisms in prostate cancer risk: Evidences from a meta-analysis

Department of Urology, Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi 214023, China.
Molecular Biology Reports (Impact Factor: 2.02). 06/2011; 39(3):2347-53. DOI: 10.1007/s11033-011-0985-x
Source: PubMed


Epidemiological studies have evaluated the association between RNASEL Asp541Glu and Arg462Gln polymorphisms and prostate cancer (PCa) risk. However, the results remain inconclusive. To derive a more precise estimation of the association between RNASEL polymorphisms and PCa risk, we performed a meta-analysis based on nineteen case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Asp541Glu and Arg462Gln polymorphisms were not associated with PCa risk (for Asp541Glu polymorphism: Glu/Glu vs. Asp/Asp: OR 1.17, 95% CI: 0.95-1.45, P = 0.13; Glu/Asp vs. Asp/Asp: OR 1.02, 95% CI: 0.92-1.14, P = 0.70; for Arg462Gln polymorphism: Gln/Gln vs. Arg/Arg: OR 0.98, 95% CI: 0.88-1.08, P = 0.62; Gln/Arg vs. Arg/Arg: OR 0.97, 95% CI: 0.91-1.04, P = 0.53). The insignificant association was maintained in the dominant and the recessive genetic models. In subgroup analyses, the significant association was not detected in Caucasian populations. However, we found the significant association of RNASEL Asp541Glu polymorphism with sporadic PCa (Glu/Glu vs. Asp/Asp: OR 1.29, 95% CI: 1.04-1.59, P = 0.02; Glu/Asp vs. Asp/Asp: OR 1.24, 95% CI: 1.03-1.50, P = 0.03). In conclusion, we found that these RNASEL polymorphisms were not related to overall PCa risk, especially in Caucasians. However, in subgroup analyses we found a suggestion that RNASEL 541Gln allele might be a low-penetrent risk factor for sporadic PCa.

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    • "RNASEL encodes riboendonuclease L (RNASEL), an enzyme activated by the interferon pathway[13]. Upon stimulation by double-stranded viral RNA, thethese studies show disparate results[14,15]; thus a definitive role for the gene and its variants in prostate carcinogenesis is lacking. IL-10 is a T H 2 cytokine, and is generally associated with the down-modulation of an inflammatory immune response[16]. "
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    ABSTRACT: Background: We previously reported that both intraprostatic inflammation and SNPs in genes involved in the immune response are associated with prostate cancer risk and disease grade. In the present study, we evaluated the association between these SNPs and intraprostatic inflammation in men without a prostate cancer diagnosis. Methods: Included in this cross-sectional study were 205 white controls from a case-control study nested in the placebo arm of the Prostate Cancer Prevention Trial. We analyzed inflammation data from the review of H&E-stained prostate tissue sections from biopsies performed per protocol at the end of the trial irrespective of clinical indication, and data for 16 SNPs in key genes involved in the immune response (IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, TNFA; 7 tagSNPs in IL10). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between carrying at least one minor allele and having at least one biopsy core (of a mean of three reviewed) with inflammation. Results: None of the SNPs evaluated was statistically significantly associated with having at least one core with inflammation. However, possible inverse associations were present for carrying the minor allele of rs2069762 (G) in IL2 (OR = 0.51, 95%CI 0.25-1.02); carrying two copies of the minor allele of rs1800871 (T) of IL10 (OR = 0.29, 95%CI 0.08-1.00); and carrying the minor allele of rs486907 (A) in RNASEL (OR = 0.52, 95%CI 0.26-1.06). After creating a genetic risk score from the three SNPs possibly associated with inflammation, the odds of inflammation increased with increasing number of risk alleles (P-trend = 0.008). Conclusion: While our findings do not generally support a cross-sectional link between individual SNPs in key genes involved in the immune response and intraprostatic inflammation in men without a prostate cancer diagnosis, they do suggest that some of these variants when in combination may be associated with intraprostatic inflammation in benign tissue. Prostate. © 2016 Wiley Periodicals, Inc.
    No preview · Article · Jan 2016 · The Prostate
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    • "Meta-analysis is a useful strategy for elucidating genetic factors in prostate cancer [55], [56]. GSTP1, which is involved in the detoxification of carcinogenic polycyclic aromatic hydrocarbons, has been investigated extensively in relation to different types of cancer, such as breast cancer [57], [58], bladder cancer [59], [60], oesophageal cancer [61], [62], and so on [5]. "
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    ABSTRACT: Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90-1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91-1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73-4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38-3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk. This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.
    Preview · Article · Aug 2013 · PLoS ONE
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    • "The polymorphism Arg462Gln in RNASEL has a higher frequency in Caucasian than African American men and is associated with increasing PCa risk in these men [209] [210], but a study among Japanese men reported the Gln462 allele decreased the risk of familial PCa [211]. Homozygous Asp541 in RNASE L is significantly less frequent in Asian than Caucasian and African men [211] [212] [213] [214]. The Asp541 allele is associated with decreasing PCa risk in African American men but increasing risk in Japanese men [211] [212]. "
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    ABSTRACT: Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second biggest cause of cancer death in men of the Western world. Higher incidences of PCa occur in men from North America, Oceania and Western countries, whereas men from Asia and North Africa have a much lower PCa incidence rate. Investigations into this population disparity of PCa incidence, in order to identify potential preventive factors or targets for the therapeutic intervention of PCa, have found differences in both environmental and genetic variations between these populations. Environmental variations include both diet and lifestyle, which vary widely between populations. Evidence that diet comes into play has been shown by men who immigrate from Eastern to Western countries. PCa incidence in these men is higher than men in their native countries. However the number of immigrants developing PCa still doesn't match native black/white men, therefore genetic factors also contribute to PCa risk, which are supported by familial studies. There are a number of genetic polymorphisms that are differentially presented between Western and Eastern men, which are potentially associated with PCa incidence. Androgen and its receptor (AR) play a major role in PCa development and progression. In this study, we focus on genes involved in androgen biosynthesis and metabolism, as well as those associated with AR pathway, whose polymorphisms affect androgen level and biological or physiological functions of androgen. While many of the genetic polymorphisms in this androgen/AR system showed different frequencies between populations, contradictory evidences exist for most of these genes investigated individually as to the true contribution to PCa risk. More accurate measurements of androgen activity within the prostate are required and further studies need to include more African and Asian subjects. As many of these genetic polymorphisms may contribute to different steps in the same biological/physiological function of androgen and AR pathway, an integrated analysis considering the combined effect of all the genetic polymorphisms may be necessary to assess their contribution to PCa initiation and progression.
    Full-text · Article · Apr 2013 · American Journal of Cancer Research
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