GSTP1 Ile105Val polymorphism and colorectal cancer risk: An updated analysis

Background

Many studies have investigated the association between the Glutathione S transferase-P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk.

Methods

Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before December 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for GSTP1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.

Results

This meta-analysis included 29 case–control studies, which included 8160 CRC cases and 10,450 controls. Overall, the variant genotypes (ValVal and IleVal) of the Ile105Val were not associated with CRC risk when compared with the wild-type IleIle homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, source of controls, study sample size and genotyping methods, no evidence of significant association was observed in any subgroup, except among those studies taking others as genotyping methods (recessive model, OR = 0.71, 95%CI = 0.52–0.96). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study.

Conclusion

This updated meta-analysis suggests that the GSTP1 Ile105Val polymorphism may not be associated with CRC risk, while the observed decrease in risk of CRC may be due to small-study bias.     

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

Background

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.

Methodology/Principal Findings

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.

Conclusions

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.     

ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis

Background and Objectives

Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the “Asian esophageal cancer belt” along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that''s explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis.

Methods

A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested.

Results

The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49–1.76) and 3.86 (2.96–5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09–84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32–78.07).

Conclusion

Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.     

GSTP1 I105V polymorphism and susceptibility to colorectal cancer in Kashmiri population

The glutathione S-transferase (GST) enzyme encoded by the GSTP1 gene is one of the critical enzymes involved in detoxification of carcinogens. The substitution of isoleucine to valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity and hence less capability of effective detoxification. Hence, we investigated the role of GSTP1 I105V polymorphism in modulating the risk of colorectal cancer (CRC) associated in a Kashmiri population. We designed a case-control study in which 86 CRC cases were studied for GSTP1 I105V polymorphism against 160 controls taken from the general population employing the polymerase chain reaction-restriction length fragment polymorphism technique. There was no significant association between GSTP1 I105V genotypes and the disease, but the Val/Val genotype was associated with an increased risk with some clinicopathological parameters (odds ratio=1.5; 95% confidence interval=0.55-4.57). This study suggests that the GSTP1 I105V polymorphism may modulate CRC risk in the Kashmiri population.     

Racial and tissue-specific cancer risk associated with PARP1 (ADPRT) Val762Ala polymorphism: a meta-analysis

The Val762Ala polymorphism poly [ADP-ribose] polymerase 1 (PARP1) gene [ADPRT (adenosine diphosphate ribosyltransferase) gene] affects enzymatic activity, which modulates cancer susceptibility among human populations. Individual data on 13,745 cases and 16,947 controls from 28 published case–control studies were re-evaluated. Odds ratios (OR) were estimated for ethnic group, cancer type, smoking joint effects and studies confined to the Hardy–Weinberg equilibrium. We applied subgroup, sensitivity and outlier analyses as well as the Bonferroni correction for multiple testing. The results show strong evidence that the variant (C) allele confers significant increased risk in the Chinese (OR 1.20–1.44, P?<?0.0001–0.002), exacerbated by smoking (OR 1.66–2.53, P?<?0.0001) and joint interaction with XRCC1 Arg399Gln (OR 1.39, P?<?0.0001) as well as adjustment for tumor type (gastric carcinoma ORs 1.39–2.01, P?<?0.0001). These significant effects were unaltered following conservative correction for multiple tests. By contrast, this procedure erased the protective significance in Caucasians, but not in two American subgroups, (i) those in the brain tumor category (0.77–0.79, P?<?0.0001) and (ii) smokers in the dominant model (OR 0.86, P?<?0.0001). These differential findings between the two ethnicities maybe correlated with significantly (P?<?0.0001) greater allele frequency of the variant allele (C) among the Chinese compared to Caucasians. Our racial and tissue-specific summary estimates imply consideration of the Val762Ala polymorphism as candidate gene marker for screening cancer patients’ best suited for PARP inhibitor therapy.     

CYP1A1 Ile462Val is a risk factor for ovarian cancer development

Published data on the association between CYP1A1 gene polymorphism and ovarian cancer risk are conflicting and heterogeneous. To derive a more precise estimation of the relationship, a meta-analysis was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for heterozygous, homozygous, dominant model, recessive model and allele, respectively. A total of 15 case-control studies were identified, among which, 13 studies (1815 cases and 3501 controls) were eligible for CYP1A1 Ile(462)Val and nine studies (2495 cases and 3553 controls) were eligible for CYP1A1 Msp1. Overall, Ile(462)Val was significantly associated with ovarian cancer, with homozygous carriers (Val/Val vs. Ile/Ile: OR=2.64; 95% CI: 1.63-4.28) and recessive model (Val/Val vs. Ile/Ile and Ile/Val: OR=2.30; 95% CI: 1.45-3.65) being risk factors for ovarian cancer development. In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (homozygous carriers: OR=4.91; 95% CI: 2.07-11.66; recessive model: OR=3.26; 95% CI: 1.41-7.50) and Asians (homozygous carriers: OR=3.06; 95% CI: 1.48-6.33; recessive model: OR=2.75; 95% CI: 1.40-5.41; Val allele: OR=1.67; 95% CI: 1.19-2.35). However, no significant associations were found between Msp1 and ovarian cancer in the overall analyses or the subgroup analyses by ethnicity. This meta-analysis denotes the importance for in-depth research regarding of gene-gene, gene-environment interactions, race-specific and histological subtypes specific to obtain a more conclusive response about the function of CYP1A1 in ovarian cancer.     

PARP-1 Val762Ala polymorphism is associated with risk of cervical carcinoma

PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47-3.70), and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47-3.70). In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with increased risk of cervical carcinoma (OR: 5.56, 95% CI: 2.08-14.3). Our results indicate that the PARP-1 Ala762Ala genotype increases the risk of cervical carcinoma.     

Association of GSTP1 Ile105Val Polymorphism and Risk of Head and Neck Cancers: A Meta-Analysis of 28 Case-Control Studies

Background and Aims

The Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC.

Method

We performed a search in the relevant electronic database and a meta-analysis based on 28 published case–control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I²-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models.

Results

The results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92–1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity.

Conclusion

This meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.     

Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: A meta-analysis

Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR) = 1.36, 95 percent confidence interval (95% CI): 1.09–1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and andenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene–gene and gene–environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.     

An updated meta-analysis of the p53 codon 72 polymorphism and gastric cancer risk

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case-control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83-1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78-0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03-1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06-1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31-8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.     

CYP1A1 MspI polymorphisms and lung cancer risk: an updated meta-analysis involving 20,209 subjects

Published data describing the association between CYP1A1 MspI gene polymorphism and lung cancer risk are inconclusive. To determine a more conclusive relationship, we performed an updated meta-analysis of all eligible studies and conducted the subgroup analysis by stratification according to the ethnicity source, histological types of lung cancer, gender and smoking status of case and control populations. A total of 51 studies comprising 20,209 subjects were included in the analysis. A significantly elevated lung cancer risk was associated with two variant genotypes (for TT vs CC: OR=1.24, 95% CI=1.11-1.40; for CT and TT combined vs CC: OR=1.19, 95% CI=1.12-1.27) in the overall population. In the stratified analysis, significantly higher risks associated with lung cancer were found in Asians, Caucasians, lung SCC, lung AC and the male population. In contrast, negligible risks were found in the mixed population, lung SCLC and the female population. Additionally, a significant association was found in the smoker population, whereas no association was found in non-smoker populations. This meta-analysis suggests that the MspI polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility, and that there is an interaction between the CYP1A1 polymorphism and smoking. However, the associations vary in different ethnic populations, histological types of lung cancer and the gender of case and control populations.     

Association of the CYP1B1 Leu432Val polymorphism with the risk of prostate cancer: a meta-analysis

Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates in endocrine-mediated tumors such as prostate cancer. The potential significance of nonsynonymous SNP Leu432Val (rs1056836) as a risk factor in prostate cancer has been extensively studied. The objective of this meta-analysis was to quantitatively summarize the association between CYP1B1 Leu432Val polymorphism and prostate cancer. All eligible studies were searched and acquired from the PubMed and ISI databases. Statistical analysis was performed by using the software STATA 11.0. Ten case-controlled studies from nine eligible publications were identified, which includes 6,668 subjects with 3,221 cases and 3,447 controls. Overall, no significant association was found between the CYP1B1 Leu432Val polymorphism and prostate cancer susceptibility for Val/Val vs Leu/Leu (OR = 1.07; 95% CI: 0.79-1.44; P = 0.67), Leu/Val vs Leu/Leu (OR = 1.05; 95% CI: 0.94-1.17; P = 0.42), Leu/Val + Val/Val vs Leu/Leu (OR = 1.07; 95% CI: 0.91-1.26; P = 0.40) and Val/Val vs Leu/Val + Leu/Leu (OR = 1.11; 95% CI: 0.86-1.44; P = 0.43). However, a higher risk was found among Asians in all genetic models (Val/Val vs Leu/Leu :OR = 2.48, 95% CI: 1.14-5.39, P = 0.02; Leu/Val vs Leu/Leu: OR = 1.40, 95% CI: 1.03-1.89, P = 0.03; Leu/Val + Val/Val vs Leu/Leu: OR = 1.51, 95% CI = 1.14-2.01, P = 0.004; Val/Val vs Leu/Val + Leu/Leu: OR = 2.50, 95% CI = 1.35-4.56, P = 0.004). We were not able to detect any association in the subgroup analysis by source of controls and genotyping method in all genetic models. In conclusion, this meta-analysis provides evidence that CYP1B1 Leu432Val polymorphism is not associated with prostate cancer risk overall with the exception in Asians.     

APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis

Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928–1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861–1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers.     

Glutathione S-transferase M1 and T1 gene polymorphism and COPD risk in smokers: an updated analysis

We evaluated the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease (COPD) in smokers. A meta-analysis of the published case–control studies was performed. Published literature was retrieved from PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI), with last update in February, 2011. Data were extracted and a fixed- or random-effects model was used to calculate pooled odds ratios with 95% confidence intervals depending on statistical heterogeneity. Fourteen eligible studies, comprising 1,665 COPD cases and 1,614 controls, were included in the meta-analysis. The combined analyses showed that there was a significant difference in GSTM1 genotype distribution between COPD cases and controls among Caucasians, but not among Asians. The combined GSTM1/GSTT1 null genotype conferred a 1.36-fold greater risk for COPD in Asian smokers. The GSTT1 null genotype alone was not associated with enhanced risk for COPD. The GSTM1 null genotype is significantly associated with an increasing susceptibility to COPD in Caucasian smokers, but not in Asian smokers. The GSTM1/GSTT1 null genotype is a significant risk factor for developing COPD in Asian smokers. The GSTT1 null genotype, however, was not associated with COPD.     

A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population

Introduction

MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.

Material and methods

The rs2910164C>G genotypes were determined in 1094 patients with lung cancer and 1100 healthy controls who were frequency matched for age and gender.

Results

The rs2910164 CG or GG genotype was associated with a significantly decreased risk for lung cancer compared to that of the CC genotype (adjusted odds ratio = 0.80, 95% confidence interval = 0.66–0.96, P = 0.02). When subjects were stratified according to smoking exposure (never, light and heavy smokers), the effect of the rs2910164C>G genotype on lung cancer risk was significant only in never smokers (adjusted odds ratio = 0.66, 95% confidence interval = 0.45–0.96, P = 0.03, under a dominant model for the C allele) and decreased as smoking exposure level increased (P_trend < 0.001). In line with this result, the level of miR-146a expression in the tumor tissues was significantly higher in the GG genotype than in the CC or CG genotype only in never-smokers (P = 0.02).

Conclusions

These findings suggest that the rs2910164C>G in pre-miR-146a may contribute to genetic susceptibility to lung cancer, and that miR-146a might be involved in lung cancer development.     

Association of CYP1A1 polymorphisms with prostate cancer risk: an updated meta-analysis

Epidemiological studies have evaluated the association between 3801T>C and 2455A>G polymorphisms of cytochrome P450 1A1 (CYP1A1) and prostate cancer risk. However, controversy exists regarding the role of these polymorphisms. In this work, a meta-analysis was performed to derive a more precise estimation of the relationship. PubMed and ISI Web databases were searched for all cases dated until March 2012. Crude odds ratios with 95?% confidence intervals were used to assess the strength of the association between CYP1A1 polymorphisms and prostate cancer risk. Sensitivity analysis, excluding the studies that deviated from the Hardy–Weinberg equilibrium (HWE), was performed. A total of 17 studies fulfilled our inclusion criteria in this meta-analysis, 12 of which were eligible (1,645 cases and 1,801 controls) for 3801T>C, and eleven (1,640 cases and 1,959 controls) were eligible for 2455A>G. Overall, the 2455A>G polymorphism resulted in a significantly increased susceptibility to prostate cancer. In addition, no significant associations between 3801T>C polymorphism and prostate cancer susceptibility were found in all genetic models. Only an elevated risk was observed for TC versus CC in Asian studies. However, no relationship was found in the Asian group for TC versus CC after excluding the studies that deviated from HWE. Thus, this meta-analysis finds the 2455A>G allele to be a risk factor for prostate cancer, whereas the 3801T>C status does not seem to be capable of modifying prostate cancer risk.     

CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR_{TC vs. TT} = 1.33, 95 % CI 1.10–1.61, P _OR = 0.004; OR_{CC+TC vs. TT} = 1.27, 95 % CI 1.05–1.55, P _OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR_{TC vs. TT} = 1.32, 95 % CI 1.04–1.67, P _OR = 0.024; OR_{CC+TC vs. TT} = 1.30, 95 % CI 1.02–1.66, P _OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR_{TC vs. TT} = 1.44, 95 % CI 1.20–1.72, P _OR < 0.001; OR_{CC+TC vs. TT} = 1.33, 95 % CI 1.12–1.58, P _OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.     

Association between complement factor H Val62Ile polymorphism and age-related macular degeneration susceptibility: A meta-analysis

Background

An increasing body of studies has assessed the contribution of Val62Ile polymorphism to age-related macular degeneration (AMD) risk, but the exact association still remains uncertain. This meta-analysis was undertaken in order to further characterize the potential association between Val62Ile polymorphism and AMD risk in four different ethnic populations.

Methods

A meta-analysis was performed using data available from 16 case–control studies evaluating correlation between the Val62Ile polymorphism and AMD in Caucasian, Chinese, Japanese and South Korean populations. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) of allele contrast and genotype contrast were estimated using the random-effects model. The Q-statistic test was used to identify heterogeneity, and the funnel plot was adopted to evaluate publication bias.

Results

Sixteen studies involving a total of 11,400 subjects based on the search criteria were included in the meta-analysis. In overall populations, the Val62Ile polymorphism seemed to be associated with AMD (OR_{AA vs. GG} = 0.40, 95% CI = 0.28–0.59; OR_{AA + GA vs. GG} = 0.72, 95% CI = 0.64–0.80; OR_{AA vs. GC + GG} = 0.50, 95% CI = 0.36–0.70; OR_{A vs. G} = 0.68, 95% CI = 0.58–0.78; OR_{GA vs. GG} = 0.71, 95% CI = 0.65–0.77). Similarly, subgroup analysis also revealed that this polymorphism was related to AMD in all ethnicities.

Conclusions

This meta-analysis suggested that Val62Ile polymorphism was associated with susceptibility to AMD.