Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: a meta-analysis

AimThe paraoxonase 1 gene (PON1, MIN: 168820) is a member of the multifactorial antioxidant enzyme paraoxonase family (EC 3.1.1.2). Two common functional single-nucleotide polymorphisms L55M (dbSNP: rs854560) and Q192R (dbSNP: rs662) have been identified in the coding region of PON1. Several studies have investigated the associations between polymorphisms of PON1 and susceptibility to breast cancer, but have yielded apparently conflicting results. We therefore carried out a meta-analysis of published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between PON1 gene variants and breast cancer risk. Method: Overall six eligible studies were identified. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using fixed and random-effect models. Results: In our meta-analysis, the presence of the R allele was associated with decreased risk of breast cancer (QR + RR compared to QQ genotype, summary OR = 0.57, 95% CI: 0.49–0.67, P < 0.001). Both heterozygosity (OR = 1.32, 95% CI: 1.10–1.58, P = 0.002) and homozygosity (OR = 2.16, 95% CI: 1.75–2.68, P < 0.001) for the 55M allele were associated with increased risk of breast cancer. Also there was a significant linear trend in risk associated with zero, one, and two 55M alleles (χ² = 54.2, P < 0.001).ConclusionThe present study showed that PON1 M and Q alleles are associated with a higher risk of breast cancer. Individuals having MM and QQ genotypes have a lower level and lower detoxification activity of the PON1 enzyme, which may increase the vulnerability of the breast to genetic damage by reducing the ability to detoxify inflammatory oxidants, as well as dietary carcinogens.     

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta-analysis

Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 −69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.     

Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

细胞色素P4501B1基因多态性与乳腺癌易感性研究进展

细胞色素P450（cytochrome,CYP）1B1是P450超基因家族酶系的一个重要成员,广泛分布于肝外组织,其代谢受到外源性致癌物、雌激素等多种因素的调控。该基因存在遗传多态性,艮前已对CYP1B1基因多态性与乳腺癌易感性进行了多项研究。本文就CYP1B1基因的多态性、调控机制及其与乳腺癌的关系进行了综述。     

Association between IL13 gene polymorphisms and susceptibility to cancer: A meta-analysis

Background/aims

Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship.

Methods

Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association.

Results

Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR = 0.82, 95%CI = 0.71–0.95; GA vs. GG: OR = 0.92, 95%CI = 0.85–0.99; GA/AA vs. GG: OR = 0.90, 95%CI = 0.85–0.97; AA vs. GG/GA: OR = 0.85, 95CI% = 0.74–0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR = 0.72, 95%CI = 0.55–0.93; CT/TT vs. TT: OR = 0.76, 95%CI = 0.62–0.89).

Conclusion

Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.     

IL6 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review

A number of case-control studies were conducted to investigate the association of IL6 gene polymorphisms with colorectal cancer (CRC). However, the results were not always consistent. We performed a systematic review and meta-analysis to examine the association between the IL6 gene polymorphisms and CRC. Data were collected from the following electronic databases: PubMed, EMBASE, Web of Science, BIOSIS Previews, HuGENet, and Chinese Biomedical Literature Database, with the last report up to July 2011. A total of 17 studies involving 4 SNPs were included (16 for rs1800795, 2 for rs1800796, 2 for rs1800797, and 1 for rs13306435). Overall, no significant association of these polymorphisms with CRC was found in heterozygote comparisons as well as homozygote comparison, dominant genetic model and recessive model. In subgroup analysis, among studies using population-based controls, fulfilling Hardy-Weinberg equilibrium, or using Taqman genotyping method, we did not find any significant association. However, the rs1800795 C allele was significantly associated with reduced risk for CRC among persons who regularly or currently took NSAIDs (four studies, OR = 0.750; 95 % CI, 0.64-0.88; P = 0.474 for heterogeneity test), and with increased risk for CRC among persons who drank (one study, OR = 1.97; 95 % CI, 1.32-2.94). Individuals with the rs1800795 C allele in the IL6 gene have a significantly lower risk of CRC, but in the setting of NSAIDs use. Further studies are merited to assess the association between the IL6 gene polymorphisms and CRC risk among persons who take NSAIDs, drink or smoke, etc.     

Association of IL-6 and MMP-3 gene polymorphisms with susceptibility to adolescent idiopathic scoliosis: a meta-analysis

Recently, several institutions have investigated the associations of MMP-3-1171 5A/6A and IL-6-174-G/C gene polymorphisms with adolescent idiopathic scoliosis (AIS), while reports from different institutions are not consistent. Therefore, we, comprehensively and systematically performed this meta-analysis to detect whether the two gene polymorphisms are correlated with AIS. From January 1994 to October 2015, all case–control studies focussed on the relationship between the two aforementioned gene polymorphisms and the susceptibility to AIS were retrieved from bibliographic databases. A total of 16 articles were found, of which five consisted of 944 cases and 1177 controls, were finally included after being assessed by two reviewers. We calculated the pooled odds ratio (OR) with 95% confidence interval (95% CI) to assess the associations. The pooled data analyses were based on allele contrast, homozygote, heterozygote, dominant and recessive models. Overall, there was no significant association of IL-6-174-G/C gene polymorphism with AIS risk. Significant association was observed in homozygote model of MMP-3-1171-5A/6A gene polymorphism (5A5A versus 6A6A: OR = 1.69, 95% CI = 1.11–2.58, P = 0.02). When stratified into Caucasian and Asian populations, positive association was found in Caucasian population (5A versus 6A: OR = 1.43, 95% CI = 1.11–1.84, P = 0.006; 5A5A versus 6A6A: OR = 1.90, 95% CI = 1.13–3.19, P = 0.015); however, there was no significant association in Asian population. The present study concluded that 5A5A genotype of MMP-3-1171 5A/6A gene polymorphism was associated with AIS, especially in Caucasian population. However, no significant association was detected between IL-6-174-G/C gene polymorphism and AIS.     

Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: A meta-analysis

Objective

The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection.

Methods

A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case–control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection.

Conclusion

Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.     

Genetic polymorphisms in the CYP1A1 and CYP1B1 genes and susceptibility to bladder cancer: a meta-analysis

The current meta-analysis of case–control studies was conducted to evaluated the relationships of genetic polymorphisms in the CYP1A1 and CYP1B1 genes with the susceptibility to bladder cancer, aiming at determine whether these polymorphisms may contribute to the pathogenesis of bladder cancer. Related articles were determined via searching the following electronic databases without any language restrictions: PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases for relevant articles published before November 1st, 2013. STATA 12.0 software was also selected to deal with statistical data. The relationships were evaluated using the pooled odds ratios (ORs) and their 95 % confidence intervals (CI). Eleven case–control studies with a total of 2,609 bladder cancer patients and 2,634 healthy subjects met the inclusion criteria. The results of our meta-analysis demonstrated that CYP1A1 genetic polymorphisms were associated with increased risks of bladder cancer (allele model: RR = 1.18, 95 % CI 1.07–1.30, P = 0.001; dominant model: RR = 1.15, 95 % CI 1.05–1.27, P = 0.003; respectively), especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effect on susceptibility to bladder cancer. The subgroup analysis results revealed positive significant correlations between CYP1A1 genetic polymorphisms and bladder cancer risk among Asians (allele model: RR = 1.26, 95 % CI 1.10–1.44, P = 0.001; dominant model: RR = 1.22, 95 % CI 1.08–1.38, P = 0.001), but not among Caucasians (all P < 0.05). Nevertheless, we observed no significant correlations between CYP1B1 genetic polymorphisms and bladder cancer risk (all P > 0.05). Our meta-analysis indicates that CYP1A1 genetic polymorphisms may be involved in the pathogenesis of bladder cancer, especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. However, CYP1B1 genetic polymorphisms may not be important determinants of bladder cancer susceptibility.     

Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population

The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3′-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case–control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P = 0.0001, OR = 0.31, 95% CI = 0.17–0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P = 0.0004, OR = 0.04, 95% CI = 0.002–0.63). p16 (540C/580T) has emerged as a major risk haplotype (P = 0.033, OR = 1.47, 95% CI = 1.05–2.07) whereas p16 (540G/580T) as a chief protective haplotype (P = 0.014, OR = 0.39, 95% CI = 0.18–0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P = 0.035, OR = 1.69, 95% CI = 1.06–2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively.     

The genetic polymorphisms of intercellular cell adhesion molecules and breast cancer susceptibility: a meta-analysis

Intercellular cell adhesion molecules (ICAMs) genetic polymorphisms have been considered to be implicated in the development of breast cancer. However, the previous reports are conflicting. Therefore, we performed a meta-analysis to assess the association between three polymorphisms, including ICAM1 K469E, ICAM5 V301I, ICAM5 rs281439, and breast cancer risk. The meta-analyses are based on a literature search of PubMed, CNKI and VIP database up until August 2011. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using review manager 5.0.25 package. In total, five populations (2,020 cases and 2,012 controls) on ICAM1 K469E polymorphism, four populations (1,797 cases and 2,244 controls) on ICAM5 V301I polymorphism and five populations (2,744 cases and 3,006 controls) on ICAM5 rs281439 variant were included. Overall, the meta-analysis showed no significant association between ICAM1 K469E polymorphism and breast cancer risk. However, a significant association was observed for ICAM5 V301I polymorphism (VV vs. II: OR = 1.48, 95 % CI 1.04–2.13, P = 0.03; VV/VI vs. II: OR = 1.25, 95 % CI 1.05–1.48, P = 0.01). In addition, there was a significant association between ICAM5 rs281439 variant and breast cancer risk (GG vs. CC: OR = 1.31, 95 % CI 1.03–1.65, P = 0.03). Our meta-analysis suggests that the ICAM5 V301I and rs281439 variants but not ICAM1 K469E polymorphism may contribute to the susceptibility of breast cancer. Given the limited sample sizes, further investigation is needed.     

Association between HOTAIR genetic polymorphisms and cancer susceptibility: A meta-analysis involving 122,832 subjects

The association between polymorphisms in HOTAIR gene and cancer susceptibility has been analyzed intensively, but the conclusions are inconsistent. Therefore, we carried out a meta-analysis aiming to assess the relationship exactly. Eligible studies were searched in PubMed and Embase databases up to October 31, 2019. Odds ratios with 95% confidence intervals were used to assess the strength of association. Sensitivity analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results. Totally, 116 studies involving 122,832 subjects were analyzed in our meta-analysis. Significant increased risk of cancer was detected for the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms. Further subgroup analyses according to cancer type revealed that different polymorphisms were associated with the risk of specific type of cancer. For example, the rs4759314 polymorphism was significantly associated with the risk of estrogen-dependent cancer, whereas the rs920778 polymorphism was associated with the risk of gastrointestinal cancer. In conclusion, our findings indicated that the rs4759314, rs920778, rs1899663, rs12826786 and rs874945 polymorphisms in HOTAIR may serve as genetic biomarkers of cancer.     

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.     

Association of VEGF gene polymorphisms with advanced retinopathy of prematurity: a meta-analysis

Published data on the association of vascular endothelial growth factor (VEGF) gene polymorphisms with retinopathy of prematurity (ROP) are inconclusive. The aim of the study was to assess the association by using meta-analysis. Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, Cochrane Library and China National Knowledge Infrastructure, with the last report up to 30 April, 2012. The odds ratio (OR) and its 95?% confidence interval (95?%CI) were used to assess the strength of the association. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. A total of 7 studies based on the search criteria were involved in this meta-analysis. Meta-analysis was performed for four VEGF gene polymorphisms (?634G/C, ?460T/C, ?2578C/A and 936C/T). Significant association was found for ?460T/C polymorphism (C vs T: OR?=?0.74, 95?%CI?=?0.57–0.95, P?=?0.02; TC+CC vs TT: OR?=?0.75, 95?%CI?=?0.47–1.21, P?=?0.24; CC vs TT+TC: OR?=?0.45, 95?%CI?=?0.26–0.76, P?=?0.003; CC vs TT: OR?=?0.45, 95?%CI?=?0.24–0.84, P?=?0.01; TC vs TT: OR?=?0.96, 95?%CI?=?0.59–1.57, P?=?0.87) in the VEGF gene, but not for other polymorphisms (?634G/C, ?2578C/A and 936C/T). This meta-analysis demonstrates that advanced ROP is associated with VEGF gene ?460T/C polymorphism, but not ?634G/C, ?2578C/A and 936C/T.     

Association between ATM polymorphisms and cancer risk: a meta-analysis

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case–control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02–1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18–1.85, AA vs. GG: OR = 1.51, 95% CI 1.18–1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62–0.92, CC vs. TT: OR = 0.80, 95% CI 0.64–0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17–1.73, CC vs. TT: OR = 1.51, 95% CI 1.21–1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20–1.63, AA vs. GG: OR = 1.37, 95% CI 1.16–1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.