The FAS ligand promoter polymorphism,rs763110 (?844C>T), contributes to cancer susceptibility: evidence from 19 case–control studies

The potentially functional polymorphism, rs763110 (−844C>T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11 105 cancer cases and 11 372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR=0.80, 95% CI: 0.68–0.95, P_{heterogeneity}=0.001; heterozygote comparison: OR=0.82, 95% CI: 0.72–0.95, P_{heterogeneity}<0.001; dominant model comparison: OR=0.82, 95% CI: 0.71–0.94, P_{heterogeneity}<0.001; and recessive model comparison: OR=0.88, 95% CI: 0.81–0.96, P_{heterogeneity}=0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk.     

Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15? Crohn's disease patients

Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn''s disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2⁻ vs NOD2⁺ CD patients, G vs A: P=0.008; OR (95% CI)=1.54 (1.10–2.15); NOD2⁻ CD patients vs controls: P=0.008; OR (95% CI)=1.37 (1.08–1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2⁻ vs 204 NOD2⁺ CD patients, G vs A: P=0.0012; OR_M-H (95% CI)=1.49 (1.17–1.90); NOD2⁻ CD patients vs controls: P=0.0007; OR_M-H (95% CI)=1.35 (1.13–1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P=0.0005; OR (95% CI)=1.52 (1.19–1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.     

Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk.Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I²=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I²=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I²=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I²=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I²=39.7%, p for heterogeneity=0.174).Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.     

Hsa-mir-499 rs3746444 polymorphism and cancer risk: a meta-analysis

MicroRNAs(miRNAs) are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English(including 6134 cases and 7141 controls) were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients(G allele vs A allele:OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%) and population-based studies(G allele vs A allele:OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%).The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.     

Association between the interaction of SMAD3 polymorphisms with body mass index and osteoarthritis susceptibility

Purpose: This study aimed to investigate the relationship between the interaction of SMAD3 polymorphisms (rs12102171 and rs2289263) with body mass index (BMI) and osteoarthritis (OA) susceptibility. Methods: This study involved 112 OA patients and 120 healthy people. The controls were frequency-matched with the cases by age and sex. Hardy-Weinberg equilibrium (HWE) was tested by χ² test in the control group. The rs12102171 and rs2289263 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relative risk of OA was represented by odds ratio (OR) with 95% confidence interval (CI) calculated by chi-squared test. Gene-environment interaction was analyzed by crossover analysis. Results: The TT genotype and T allele of SMAD3 rs12102171 polymorphism were more frequent in case than control groups (P=0.04 in both of two polymorphisms), which increased the risk of OA (OR=3.39, 95% CI=1.03-11.11 and OR=1.64, 95% CI=1.03-2.59). GG genotype and G allele were also the risk factors for OA (OR=3.22, 95% CI=1.09-9.51 and OR=1.57, 95% CI=1.02-2.42). The BMI had interactions with genotype CC and CT+TT of rs12102171 and TT and TG+GG of rs2289263 (rs12102171: OR=2.15, P=0.02 and OR=3.99, P=1.00×10^-3; rs2289263: OR=2.73, P=4.00×10^-3 and OR=4.67, P=0). Conclusions: CC and CT+TT and TT and TG+GG genotypes of SMAD3 rs12102171 and rs2289263 polymorphisms together with BMI may be susceptible factors to OA, and interactions there between can possibly confer risk to OA.     

Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI

The goal of this study is to investigate the relationship between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and body mass index (BMI) in two sizable and well-characterized populations of British women: the British Women''s Heart and Health Study (BWHHS) (age 60–79 years) and the mothers from the Avon Longitudinal Study of Parents and Children (age 16–44 years). We genotyped the Val66Met polymorphism (rs6265) in these two populations, and conducted a linear regression analysis to test for an association between this polymorphism and BMI. Both study populations indicated an association between BMI and the Val66Met polymorphism, with individuals carrying the Met–Met genotype having a lower mean BMI than those with the Val–Met or Val–Val genotypes (in the BWHHS): mean BMI difference=−0.911 kg/m², 95% confidence interval (CI): −1.70 to −0.12, P=0.023; in the mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC): mean BMI difference=−0.57 kg/m², 95%CI: −1.08 to −0.054, P=0.03). In a pooled analysis of these two studies, together with one further published study that provided data in a suitable format for inclusion in our meta-analysis, we found a pooled difference of −0.76 (95% CI: −1.16, −0.036) for adult women; I²–test for heterogeneity=51%, P=0.13. Our study indicated an association between BDNF and BMI in two general population studies of women. The exact role of BDNF in weight regulation merits further investigation.     

Association of a common genetic variant in prostate stem cell antigen with cancer risk

Introduction

Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.

Material and methods

To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects.

Results

The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09–1.42, p_{heterogeneity} < 0.001, I² = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04–1.11, p_{heterogeneity} = 0.108, I² = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16–2.81, p_{heterogeneity} < 0.001, I² = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95–1.74, p_{heterogeneity} < 0.001, I² = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies.

Conclusions

In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.     

Association of the TGF-�� receptor genes with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a multifactorial condition. The transforming growth factor β (TGF-β) pathway regulates vascular remodeling and mutations in its receptor genes, TGFBR1 and TGFBR2, cause syndromes with thoracic aortic aneurysm (TAA). The TGF-β pathway may be involved in aneurysm development in general. We performed an association study by analyzing all the common genetic variants in TGFBR1 and TGFBR2 using tag single nucleotide polymorphisms (SNPs) in a Dutch AAA case–control population in a two-stage genotyping approach. In stage 1, analyzing 376 cases and 648 controls, three of the four TGFBR1 SNPs and nine of the 28 TGFBR2 SNPs had a P<0.07. Genotyping of these SNPs in an independent cohort of 360 cases and 376 controls in stage 2 confirmed association (P<0.05) for the same allele of one SNP in TGFBR1 and two SNPs in TGFBR2. Joint analysis of the 736 cases and 1024 controls showed statistically significant associations of these SNPs, which sustained after proper correction for multiple testing (TGFBR1 rs1626340 OR 1.32 95% CI 1.11–1.56 P=0.001 and TGFBR2 rs1036095 OR 1.32 95% CI 1.12–1.54 P=0.001 and rs4522809 OR 1.28 95% CI 1.12–1.46 P=0.0004). We conclude that genetic variations in TGFBR1 and TGFBR2 associate with AAA in the Dutch population. This suggests that AAA may develop partly by similar defects as TAA, which in the future may provide novel therapeutic options.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.     

Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis

A recent genome-wide association study conducted by the International Multiple Sclerosis Genetic Consortium (IMSGC) identified, among others, a number of putative multiple sclerosis (MS) susceptibility variants at position 1p22. Twenty-one SNPs positively associated with MS were located at the GFI-EVI5-RPL5-FAM69A locus. In this study, we performed an analysis and fine mapping of this locus, genotyping eight Tag-SNPs in 732 MS patients and 974 controls from Spain. We observed an association with MS in three of eight Tag-SNPs: rs11804321 (P=0.008, OR=1.29; 95% CI=1.08–1.54), rs11808092 (P=0.048, OR=1.19; 95% CI=1.03–1.39) and rs6680578 (P=0.0082, OR=1.23; 95% CI=1.07–1.41). After correcting for multiple comparisons and using logistic regression analysis to test the addition of each SNP to the most associated SNPs, we observed that rs11804321 alone was sufficient to model the association. This Tag-SNP captures two SNPs in complete linkage disequilibrium (r²=1), both located within the 17th intron of the EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that points to EVI5 as a factor of susceptibility to MS.     

APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis

Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28–0.78) and 0.92 (95% CI: 0.86–0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70–0.92) and 0.91 (95% CI: 0.77–0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39–0.53; specificity 0.87, 95% CI: 0.64–0.96; tissue: sensitivity 0.87, 95% CI: 0.72–0.94; specificity 0.89, 95% CI: 0.68–0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR)=24.91, 95% CI: 12.86–48.24, I²=72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88–75.59; I²=70.7%) and 8.20 (95% CI: 2.84–23.74, I²=64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.     

The PD-1 rs36084323 A > G polymorphism decrease cancer risk in Asian: A meta-analysis

The rs36084323 A?>?G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A?>?G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR?=?0.89, 95%CI:0.81–0.97, P?=?0.008, I²?=?48.8%; GG vs. AA, OR?=?0.79, 95% CI:0.66–0.94, P?=?0.008, I²?=?48.7%; GG/AG vs. AA, OR?=?0.87, 95%CI:0.76–0.98, P?=?0.017, I²?=?34.9%; GG vs. AG/AA, OR?=?0.85, 95%CI:0.75–0.97, P?=?0.027, I²?=?40%) and in the patients with EOC(AG vs. AA, OR?=?0.69, 95%CI:0.54–0.90, P?=?0.005, I²?=?0%; GG/AG vs. AA, OR?=?0.67, 95%CI:0.52–0.85, P?=?0.001, I²?=?0). Meta-regression showed that ethnicity (P?=?0.029) but not cancer types (P?=?0.792), source of controls (P?=?0.207) or ample size (P?=?0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A?>?G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.     

Impacts of CD152 polymorphisms on cervical cancer susceptibility

AimThe objective of this study was to discuss the effect of CD152 polymorphisms rs231775, rs3087243 and rs5742909 on the susceptibility to cervical cancer.MethodsThe databases of PubMed, EMBASE, Cochrane Library, ISI Web of Science, Google Scholar Web, CNKI and Wanfang were searched for eligible studies. Chi-square-based Q test examined heterogeneity between included studies, and when P_{heterogeneity} was less than 0.05, random-effect model was used to calculate odds ratios (ORs) with their 95 % confidence intervals (95 % CIs); or else, fixed-effect model was selected. Sensitivity analysis was implemented to determine the stability of final results through removing enrolled studies one at a time and then re-obtaining overall estimates. Publication bias among included studies was checked employing Begg’s funnel plot and Egger’s test.ResultsCD152 polymorphism rs231775 decreased cervical cancer risk in total analysis under the genetic models of GG vs. AA, GG vs. AA + AG and G vs. A (OR = 0.73, 95 % CI = 0.59–0.91; OR = 0.78, 95 % CI = 0.65–0.94; OR = 0.92, 95 % CI = 0.87–0.98), and so did the polymorphism rs3087243 in total analysis under the comparisons of AA vs. GG, AA + GA vs. GG, AA vs. GG + GA, A vs. G and GA vs. GG (OR = 0.51, 95 % CI = 0.42–0.60; OR = 0.71, 95 % CI = 0.62–0.82; OR = 0.57, 95 % CI = 0.50–0.66; OR = 0.70, 95 % CI = 0.64–0.77; OR = 0.83, 95 % CI = 0.72–0.97). Besides, the polymorphism rs5742909 elevated the disease onset in total analysis under the contrasts of TT vs. CC, TT + CT vs. CC, TT vs. CC + CT, T vs. C and CT vs. CC (OR = 2.66, 95 % CI = 1.75–4.04; OR = 1.54, 95 % CI = 1.24–1.91; OR = 2.13, 95 % CI = 1.12–4.03; OR = 1.44, 95 % CI = 1.17–1.78; OR = 1.49, 95 % CI = 1.22–1.83).ConclusionCD152 polymorphisms rs231775 and rs3087243 significantly decrease the risk of cervical cancer, while rs5742909 may increase the disease risk.     

PIK3CA polymorphisms associated with susceptibility to hepatocellular carcinoma

Purpose: Our study was carried out to explore the relationship of PIK3CA rs17849071 and rs17849079 polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese Han population. Methods: 150 HCC patients and 152 healthy individuals were recruited in the case and control groups respectively. The genotypes of PIK3CA rs17849071 and rs17849079 polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The linkage disequilibrium and haplotypes were analyzed with Haploview software. Differences in frequencies of genotypes, alleles, and haplotypes between the case and control groups were checked with χ² test. The controls were matched with the cases in age and gender. The relative risk of HCC was represented by odds ratio (OR) and 95% confidence interval (95% CI). Results: Significant difference in frequencies of GG genotype and G allele in PIK3CA rs17849071 polymorphism existed between the two groups (P=0.040; P=0.028), indicating that rs17849071 was closely related to the increased risk of HCC (OR=2.919, 95% CI=1.007-8.460; OR=1.642, 95% CI=1.051-2.564). Furthermore, TT genotype also significantly increased the susceptibility to HCC (OR=3.438, 95% CI=1.050-11.250) and so was T allele (OR=1.521, 95% CI=1.052-2.199). The haplotype analysisshowed that G-T haplotypes were higher in cases than that of controls (P=0.030), which suggested that G-T might be a susceptible haplotype to HCC. Conclusions: The PIK3CA rs17849071 and rs17849079 polymorphisms may increase the risk of HCC either independently or synergistically.     

A meta-analysis of DNA repair gene <Emphasis Type="Italic">XPC</Emphasis> polymorphisms and cancer risk

Polymorphisms (A33512C, C21151T and PAT −/+) of the xeroderma pigmentosum group C (XPC) were shown to contribute to genetic susceptibility to cancer. However, association studies on these polymorphisms in cancer have shown conflicting results. Thus, we performed a meta-analysis. Overall, there was no significant association between 33512C (9,091 patients and 11,553 controls) and cancer risk. No significant association was found in stratification analysis by tumor sites and ethnicities except an elevated lung cancer risk under the recessive genetic model in all subjects [P = 0.04, odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.00–1.45, P _{heterogeneity} = 0.88]. There was no significant association between 21151T (5,227 patients and 5,959 controls) and cancer risk in all subjects but an increased cancer risk in Caucasians under the recessive genetic model (P = 0.006, OR = 1.45, 95% CI 1.11–1.90, P _{heterogeneity} = 0.75) and homozygote comparison (P = 0.02, OR = 1.41, 95% CI 1.07–1.81, P _{heterogeneity} = 0.41). It might be that 21151T increases bladder cancer risk under the recessive genetic model (P = 0.02, OR = 1.49, 95% CI 1.06–2.09, P _{heterogeneity} = 0.47) and homozygote comparison (P = 0.02, OR = 1.49, 95% CI 1.05–2.11, P _{heterogeneity} = 0.23). There was no significant association between PAT + (4,600 patients and 4,866 controls) and cancer risk in all subjects. An increased cancer risk in Caucasians was found under the recessive genetic model (P = 0.02, OR = 1.20, 95% CI 1.03–1.40, P _{heterogeneity} = 0.37) and homozygote comparison (P = 0.008, OR = 1.26, 95% CI 1.06–1.50, P _{heterogeneity} = 0.13). The XPC PAT + allele might increase head and neck cancer risk (P = 0.02, OR = 1.29, 95% CI 1.04–1.59, P _{heterogeneity} = 0.15). More studies based on larger, stratified, case–control population, especially studies investigate the combined effect of XPC A33512C, C21151T, and PAT, are required to further evaluate the role of these polymorphisms in different cancers.     

Association between p53 Pro72Arg polymorphism and prostate cancer risk:a meta-analysis

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios (RR) with 95% confidence intervals (CIs) were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found (Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, P heterogeneity = 0.016, I 2 = 55.8%; Pro/Pro+Pro/Arg vs Arg/ Arg, RR = 1.05, 95%CI=1.00-1.11, P heterogeneity = 0.077, I 2 = 51.1%). In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model (RR = 0.31, 95%CI=0.10-0.91, P heterogeneity = 0.110, I 2 =60.8%). This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.     

Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility

Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in sub-Saharan Africa was because of the 202A/376G G6PD A− allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are relatively common in some regions of West Africa. To investigate the consequences of unrecognized allelic heterogeneity on association studies, in particular studies of G6PD deficiency and malaria, we carried out a case–control analysis of 2488 Gambian children with severe malaria and 3875 controls. No significant association was found between severe malaria and the 202A/376G G6PD A− allele when analyzed alone, but pooling 202A/376G with other deficiency alleles revealed the signal of protection (male odds ratio (OR) 0.77, 95% CI 0.62–0.95, P=0.016; female OR 0.71, 95% CI 0.56–0.89, P=0.004). We have identified the 968C mutation as the most common G6PD A− allele in The Gambia. Our results highlight some of the consequences of allelic heterogeneity, particularly the increased type I error. They also suggest that G6PD-deficient male hemizygotes and female heterozygotes are protected from severe malaria.     

CYP17 T27C polymorphism and prostate cancer risk: a meta-analysis based on 31 studies

Objective

The cytochrome P450 17α-hydroxylase (CYP17) plays a vital role in androgen biosynthesis. A T-to-C polymorphism in the 5′ promoter region of CYP17 has been implicated as a risk factor for prostate cancer, but the results of individual studies are inconclusive or controversial. To derive a more precise estimation of the relationship, we performed an updated meta-analysis from 31 studies based on 27 publications.

Methods

A comprehensive search was conducted to examine all the eligible studies of CYP17 polymorphism and prostate cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association.

Results

Overall, individuals with CC/CT genotype were not associated with prostate cancer risk (CC vs. TT: OR = 1.03, 95% CI = 0.86-1.24, P = 0.72, P_{heterogeneity} < 0.0001; CT vs. TT: OR = 0.99, 95% CI = 0.87-1.12, P = 0.88, P_{heterogeneity} = 0.0006). In the stratified analysis by ethnicity, there was a significantly increased risk of prostate cancer among individuals of African descent under the recessive model (OR = 1.56, 95% CI = 1.01-2.39, P = 0.04, P_{heterogeneity} = 0.65).

Conclusion

This meta-analysis suggested that CYP17 polymorphism might be associated with prostate cancer risk among individuals of African descent.     

RET polymorphisms might be the risk factors for thyroid cancer

Aims: The purpose of the study is to investigate the relationship between rs1799939, rs1800858 and rs74799832 polymorphisms of RET with thyroid cancer (TC) susceptibility. Methods: Genotypes distribution of control groups were tested by Hardy-Weinberg equilibrium (HWE). Rs1799939, rs1800858 and rs74799832 polymorphisms of RET were researched in 135 patients with TC and 135 healthy people using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the association between RET polymorphisms and the risk of TC by Chi-squared test. Results: Genotypes frequencies of the control group were consistent with HWE. The frequency of genotype AA and allele A in rs1799939 were significantly higher in patients with TC than controls (OR=3.768, P=0.046; OR=1.695, P=0.035). Genotype GG and allele G of rs1800858 remarkably increased the risk of TC (OR=2.149, P=0.039; OR=1.45, P=0.039). Moreover, CC genotype and C allele in rs74799832 polymorphism was related with TC susceptibility. (OR=2.28, P=0.049; OR=1.566, P=0.049). Conclusion: In present result, RET rs1799939, rs1800858 and rs74799832 polymorphisms might be the risk factors for TC.     

Genetic association between CD44 polymorphisms and chronic hepatitis B virus infection in a Chinese Han population

Aims: This article aimed at discussing the association of chronic hepatitis B virus (HBV) infection with CD44 polymorphisms in Chinese Han population; meanwhile, the interaction of polymorphisms was also analyzed based on chronic HBV infection. Methods: The genotyping of CD44 polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 108 HBV infected and 130 healthy persons. The genotype distributions of CD44 rs187115, rs13347 in the control group were checked by Hardy-Weinberg equilibrium (HWE). The strength of the relevance between polymorphism and disease was measured by odds ratio (OR) with corresponding 95% confidence interval (CI) calculated by χ² test. The 2×4 crossover analysis method was used to conduct the interaction analysis of polymorphisms. Results: The genotype distributions in controls conformed to HWE. GG genotype and G allele frequencies in rs187115 were obviously higher in cases than the controls (P=0.02, 0.04). Compared with the common genotype CC, individual who carried mutant genotypes (CT and TT) of rs13347 had a significantly high risk to suffer from HBV infection (OR=1.99, P=0.02 for CT; OR=3.56, P=3.00×10^-3 for TT), furthermore, CT+TT genotype also showed a high susceptibility (OR=2.27, P=2.00×10^-3). Similarly, T allele of rs13347 increased 0.98 times risk in cases compared with controls (OR=1.98, 95% CI=1.34-2.92). The two polymorphisms in CD44 presented a positive interaction. Conclusion: CD44 polymorphisms are associated with chronic HBV infection as the risk factors, and the synergistic action is also found between the two polymorphisms.