Rs895819 within miR-27a Might be Involved in Development of Non Small Cell Lung Cancer in the Chinese Han Population

MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development ofvarious cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation oraberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small celllung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility andprognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjustedodds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the associationbetween rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG ofrs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26,95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA).Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjustedOR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However,no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant andrecessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not inprogression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might begenetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospectivestudies as well as functional studies are warranted to verify our findings.     

Association Between the Pre-mir-218 Polymorphism and Cancer Risk in the Chinese Population: a Meta-Analysis

Background: Several recent studies have explored associations between pre-mir-218 polymorphism(rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimationof the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials andMethods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China NationalKnowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies wereanalyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs)and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showedthat the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versusAA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96),and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models(GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significantassociation between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in allcomparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10;GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: Thefindings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development inChinese. However, well-designed studies with larger sample size and more detailed data are needed to confirmthese conclusions.     

2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国东北汉族绝经前妇女乳腺癌风险关系

背景与目的：乳腺癌作为中国女性最常见的恶性肿瘤,每年的新发数量和死亡数量分别占全世界的12.2%和9.6%,但与中国乳腺癌患者明显相关的基因多态位点至今尚不清楚。本研究旨在探讨2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国北方汉族绝经前妇女乳腺癌风险关系,为预防和治疗乳腺癌提供循证依据。方法：采用多重单碱基延伸单核苷酸多态性分型技术(SNaPshot)分析方法,检测了280例绝经前乳腺癌患者和287例绝经前正常对照者2q35 rs13387042和8q24 rs13281615多态性位点基因型,并比较不同基因型和等位基因与乳腺癌风险的关系。结果：2q35 rs13387042多态性位点基因型频率在乳腺癌和对照样本之间差异有统计学意义(P=0.017);8q24 rs13281615多态性位点基因型频率在乳腺癌和对照样本之间差异无统计学意义(P=0.967)。Logistic回归分析结果显示,对于2q35 rs13387042位点,与GG相比,GA和GA+AA基因型携带者显著增加乳腺癌的患病风险(OR=1.793,95%CI：1.177～2.733,P=0.007;OR=1.691,95%CI：1.122～2.550,P=0.012),而AA携带者与乳腺癌的患病风险无关(OR=0.572,95%CI：0.104～3.153,P=0.521);与G等位基因相比,A等位基因显著增加乳腺癌的患病风险(OR=1.505,95%CI：1.033～2.193,P=0.033)。对于8q24rs13281615位点,与AA相比,AG、GG和AG+GG基因型携带者与乳腺癌的患病风险无关(OR=0.992,95%CI：0.660～1.490,P=0.968;OR=1.047,95%CI：0.642～1.708,P=0.853;OR=1.007,95%CI：0.682～1.487,P=0.971);与A等位基因相比,G等位基因不增加乳腺癌患病风险(OR=1.021,95%CI：0.809～1.288,P=0.863)。结论：本实验证实2q35 rs13387042多态性位点能够增加中国北方汉族绝经前妇女乳腺癌易感风险,而8q24 rs13281615多态性位点与中国北方汉族绝经前妇女乳腺癌易感性无明显相关性。     

Association between IL-27 Gene Polymorphisms and Cancer Susceptibility in Asian Population: A Meta-Analysis

Background: Interleukin 27 (IL-27) has potent antitumor activity. Several epidemiological studies have designated that genetic variants of the IL-27 gene may contribute to various cancer susceptibility, but the data were inconclusive.  Objective: The current meta-analysis aimed to address the association between IL-27 rs153109, rs17855750, and rs181206 polymorphisms and the risk of cancer. Data Sources: Our team has selected eligible studies up to May 1, 2020, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. Results: Our meta-analysis revealed that the carriers rs153109 A>G polymorphism in the IL-27 gene have higher risks of diseases in the heterozygous (OR=1.26, 95%CI=1.06-1.49, P=0.007, AG vs AA), homozygous (OR=1.18, 95%CI=1.01-1.37, p=0.33, GG vs AA), dominant (OR=1.25, 95%CI=1.07-1.47, P=0.006, AG+GG vs AA), and allele (OR=1.15, 95%CI=1.04-1.27, P=0.008, G vs A) genetic models. Stratified analysis by cancer type indicated that this variant was significantly associated with gastrointestinal cancer, colorectal cancer and breast cancer. The findings did not support an association between rs17855750 T>G, rs181206 T>C polymorphisms of IL-27 and cancer risk. Conclusion: the current study findings suggest that IL-27 rs153109 polymorphism significantly increased the risk of cancer susceptibility. Well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities is required to verify the findings.     

Lack of Association between Hsa-Mir-499 rs3746444 Polymorphism and Cancer Risk: Meta-analysis Findings

Epidemiologic findings concerning the association between the hsa-mir-499 rs3746444 A>G polymorphismand cancer risk have yielded mixed results. We aimed to investigate the association by performing a meta-analysisof all available studies. We searched PubMed and EMBASE for studies published up to November 2014, usingodds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. The Benjamini-Hochberg (BH) method was used to correct the p values for multiple comparisons. We included 39 studies,including 14,136 cases and 16,937 controls. The results of overall meta-analysis suggested a borderline associationbetween hsa-mir-499 rs3746444 polymorphism and cancer susceptibility (AG+GG vs. AA: OR=1.15, 95% CI=1.04-1.26, corrected p value=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium(HWE), however, this association disappeared (AG+GG vs AA: OR=1.18, 95% CI=1.03-1.34, corrected pvalue=0.21). When stratified analysis by ethnicity, cancer type or HWE in controls, although some associationsbetween hsa-mir-499 rs3746444 polymorphism and cancer susceptibility were detected, these associations nolonger existed after adjustment using BH method. In conclusion, our meta-analysis suggests that hsa-mir-499rs3746444 A>G polymorphism is not associated with risk of cancer based on current evidence.     

N-Acetyltransferase 2 Gene Polymorphisms are Associated with Susceptibility to Cancer: a Meta-analysis

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism ofvarious potential carcinogens. In recent years, a number of studies have been carried out to investigate therelationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populationsfor different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysisto further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studiesinvolving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. Wealso evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparentsignificant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GAvs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-basedcontrols (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast,a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancersusceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95%CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94)and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94).We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associatedwith a decreased risk of cancer and is likely a protective factor against cancer development.     

Association of a Pre-miR-27a Polymorphism with Cancer Risk: an Updated Meta-analysis

MicroRNA-27a is highly expressed in cancers and has been identified as an oncogenic microRNA. A geneticvariant in pre-miR-27a (rs895819) with a transition of A to G has been demonstrated to be associated with cancerrisk; however, the results of these studies remain conflicting rather than conclusive. Therefore, we performed ameta-analysis to derive a more precise estimation. Through searching PubMed or other databases up to March2014 using the following MeSH terms and keywords, “miR-27a”, “polymorphism” and “cancer”, seventeencase-control studies were identified in this meta-analysis, including 7,813 cases and 9,602. Crude odds ratios(ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the association strengthbetween rs895819 and the susceptibility of cancer. The results of the overall meta-analysis did not suggest anyassociation between rs895819 polymorphism and cancer susceptibility, and this remained in Asians as a subgroup.In Caucasians, however, the rs895819 was associated with a reduced cancer risk in heterozygous (OR,0.83; 95%CI, 0.75-0.93) and dominant models (OR, 0.84; 95%CI, 0.76-0.93), and the [G] allele of rs895819showed a protective effect (OR, 0.90, 95%CI, 0.84-0.97). Further studies showed a significant association betweenthe [G] allele of rs895819 and decreased risk of breast cancer (0.91; 95%CI, 0.85-0.98), and stratified analysesindicated a protective effect of the [G] allele in Caucasians (OR, 0.89; 95%CI, 0.82-0.98), younger breast cancercases (OR, 0.87; 95%CI, 0.79-0.96), and in the group of unilateral breast cancer patients (OR, 0.90; 95%CI,0.83-0.97). These findings suggest an association between pre-miR-27a polymorphism rs895819 and cancer riskin Caucasians. The protective effect of rs895819 [G] allele in younger breast cancer and in the group of unilateralbreast cancer patients await further confirmation since the included studies in this meta-analysis were limited.     

A specific diplotype defined by PPP1R13L rs1970764, CD3EAP rs967591 and ERCC1 rs11615 and lung cancer risk in a Chinese population

Haplotypes defined by multiple loci may be more precise and useful than genotypes in providing risk estimates for particular cancers. Diplotype is defined as a specific combination of two haplotypes. A Chinese case-control analysis comprising 370 cases and 388 controls was conducted to evaluate the effects of the high-risk diplotype predefined as PPP1R13L rs1970764(AA)-CD3EAP rs967591(GG)-ERCC1 rs11615(AA) among Caucasians and three SNPs alone or other haplotypes combined for lung cancer risk. Both the variant G-allele of PPP1R13L rs1970764 and the variant A-allele of CD3EAP rs967591 were significantly over-represented among cases (P=0.03 and P=0.002, respectively). The variant GG-homozygotes of PPP1R13L rs1970764 had increased risk [GG versus AA: adjusted OR (95% CI)=1.30 (1.04-1.62), P=0.02]. The carriers of variant A-allele of CD3EAP rs967591 also presented increased risk [AA versus GG: adjusted OR (95% CI)=1.40 (1.12-1.75), P=0.004; AG versus GG: adjusted OR (95% CI)=1.47 (1.05-2.07), P=0.03 and AG+AA versus GG: adjusted OR (95% CI)=1.26 (1.07-1.48), P=0.005]. Interaction between CD3EAP rs967591 and smoking duration was observed (P=0.003). Only haplotype 1 (the common haplotype) defined as PPP1R13L rs1970764(G)-CD3EAP rs967591(A)-ERCC1 rs11615(G) showed marginally increased risk [OR (95% CI)=1.38 (1.09-1.75), P=0.009] after Bonferroni correction. The frequency of the high-risk diplotype predefined among Caucasians was 1% in controls and no significant evidence of the diplotype distribution between cases and controls was detected in present study. In conclusion, we found that variant alleles of PPP1R13L rs1970764 and CD3EAP rs967591 may contribute to risk factors of lung cancer, but the high-risk diplotype predefined among Caucasians was rare and the diplotype is unlikely to confer lung cancer risk in a Chinese population.     

Association of mir-499 and mir-149 Polymorphisms with Cancer Risk in the Chinese Population: Evidence from Published Studies

Meta-analyses have shown that microRNA polymorphisms have variable effects in different population. Yet,no meta-analysis investigated the association of two common polymorphisms of miRNA, mir-499 rs3746444polymorphism and mir-149 rs2292832 polymorphism, with cancer risk in the Chinese population. We searchedthe PubMed, Web of Knowledge, MEDLINE, CNKI databases, as well as Cochrane library, updated on December31, 2012 for assays regarding cancer risk association with these two common polymorphisms in the presentmeta-analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to explore the strengthof associations. The results showed that rs3746444 polymorphism was associated with increased cancer risk(dominant model: GG/AG vs. AA: OR = 1.43, 95% CI: 1.14-1.80; recessive model: GG vs. AG/AA: OR = 1.54,95% CI: 1.04-2.30; homozygote model: GG vs. AA: OR = 1.69, 95% CI: 1.10-2.60; heterozygote model: AG vs.AA: OR = 1. 35, 95% CI: 1.09-1.67), and rs3746444 was associated with liver cancer in the subgroup of cancertypes. For the rs2292832 polymorphism, the results showed no significant risk association in both overall pooledanalysis and subgroup of cancer types, smoking status, gender and tea drinking status in the Chinese population.This meta-analysis suggested that the rs3746444 GG genotype is associated with increased cancer risk, especiallyliver cancer, while the rs2292832 polymorphism showed no association with cancer risk in Chinese.     

pre-miR-27a单核苷酸多态与非吸烟女性肺癌发生的相关性

目的:探讨miR-27a(rs895819,A>G)多态与非吸烟女性肺癌发生的相关性。方法:采用病例-对照研究方法,使用PCR-RFLP技术检测90例非吸烟女性原发性肺癌患者和97例非吸烟女性体检者rs895819位点基因型分布频率。非条件Logistic统计分析不同基因型与肺癌发生的相关性,并分析该多态与烹饪油烟暴露的协同效应及与临床参数的相关性。结果:肺癌组rs895819 位点GG突变基因型和G等位基因频率明显高于对照组(P=0.047,P=0.016)。AG+GG基因型明显增加了非吸烟女性肺癌的发生风险(OR=1.82,95%CI=1.01～3.28,P=0.038)。肺癌组和对照组烹饪油烟暴露率分别为57%和42%,差异有统计学意义(P=0.035)。回归分析显示该多态位点与烹饪油烟无交互作用;与临床病理特征(病理类型,临床分期和淋巴结转移)均无相关性。结论:has-miR-27a rs895819 G等位基因增加了非吸烟女性肺癌发生的风险。     

Association between the Interleukin-17A -197G>A (rs2275913) Polymorphism and Risk of Digestive Cancer

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation andprogression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913)polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the roleof this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic reviewand meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were usedto estimate the strength of the association. The results of overall analyses indicated that the variant A allele wasassociated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA:OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specificcancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28;AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, therewas evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG:OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13-1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasianpopulations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). Inconclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to anincreased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastriccancer.     

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphismwith risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the presentmeta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science,EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORsand their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancerrisk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overallrisk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG)genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition,no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and alteredcancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggestedthat AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-typeGG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele ofERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer comparedwith G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with theAA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype;The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future largescalestudies performed in multiple populations are warranted to confirm our results.     

Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies

Background: Previous epidemiological studies have suggested a potential role of the HSPA1B±1267A/G polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ±1267A/G was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p< 0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ±1267A/G polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.     

Association of common PALB2 polymorphisms with breast cancer risk: a case-control study

PURPOSE: The PALB2 gene has an essential role in BRCA2-mediated DNA double-strand break repair and intra-S phase DNA damage checkpoint control, and its mutations are moderately associated with breast cancer susceptibility. This study was designed to investigate the common variants of PALB2 and their association with breast cancer risk. EXPERIMENTAL DESIGN: Four single nucleotide polymorphisms (SNP; rs249954, rs249935, rs120963, and rs16940342) which tagged all 19 of the reported SNPs (minor allele frequency >0.05) covering PALB2 were selected and genotyped in 1,049 patients with breast cancer and 1,073 cancer-free controls in a female Chinese population. RESULTS: Based on the multiple hypothesis testing with the Benjamini-Hochberg method, tagging SNPs (tSNP) rs249954, rs120963, and rs16940342 were found to be associated with an increase of breast cancer risk (false discovery rate-adjusted P values of 0.004, 0.028, and 0.049, respectively) under the dominant model. tSNP rs249954 was associated with a 36% increase of breast cancer risk [adjusted odds ratio (OR), 1.36; 95% confidence intervals (CI), 1.13-1.64; P = 0.001; TT/TC versus CC genotypes]. The adjusted OR for rs120963 was 1.25 (95% CI, 1.04-1.49; P = 0.014; CC/CT versus TT genotypes). For rs16940342, the adjusted OR was 1.21 (95% CI, 1.02-1.45; P = 0.037; GG/GA versus AA genotypes). Based on an additive model, tSNPs rs249954 and rs120963 were associated with an increase of breast cancer risk (P = 0.005 and 0.019; respectively), with the false discovery rate-adjusted P values being 0.020 and 0.038, respectively. CONCLUSIONS: Our data suggest that the variants of PALB2 confer low-penetrance breast cancer susceptibility in a Chinese population.     

8q24rs13281615单核苷酸多态性与乳腺癌发病风险的Meta分析

目的:探讨8q24 rs13281615单核苷酸多态性(single nucleotide polymorphism,SNP)与乳腺癌发病风险的关系.方法:检索PubMed、Medline、Embase、中国知网(China National Knowledge Infrastructure,CNKI)和万方数字化期刊等中英文数据库.以乳腺癌病例组和对照组人群基因型分布计算粗比值比(odds ratios,OR)和95％可信区间(95％ confidence interval,CI),采用RevMan 5.1软件进行Meta分析和文献偏倚的评估.结果:共纳入7篇研究文献,累积病例22 128例,累积对照29 276例.采用随机效应模型,与野生纯合子(AA)相比,携带杂合子(AG)和突变纯合子(GG)的妇女发生乳腺癌的合并风险上升(OR=1.14,95％CI:1.04～1.25),尤其是欧洲妇女乳腺癌的发病风险增加(OR=1.14,95％CI:1.02～1.28).结论:8q24 rs13281615的G等位基因型可能会增加乳腺癌的发病风险.     

Association Analysis of GSTP1-rs1695 Polymorphism with the Risk of Oral Cancer: A Literature Review,an Updated Meta- Analysis,and a Structural Assessment

Background: This study aimed to investigate the association of rs1695 polymorphism in glutathione S-transferase P1 (GSTP1) with risk of oral cancer in a meta-analysis which was followed by a bioinformatics approach. Materials and methods: Related articles were collected through a systematic search in PubMed, Google Scholar, and EMBASE databases up to June 2022 and then screened. Finally, seven studies, including 1249 cases of oral cancer and 1861 healthy individuals, were included in our meta-analysis. Seven different genetic models including G vs. A, GG+GA vs. AA, GG vs. GA+AA, GA vs. GG+AA, GG vs. GA, GG vs. AA, and GA vs. AA were used for the calculation of odds ratio and 95% confidence interval in order to assess the association between GSTP1-rs1695 polymorphism and oral cancer risk. Also, the ethnicity-based stratified analyses were performed using the seven mentioned models. Some bioinformatics software was used to investigate the effect of rs1695 polymorphism on the primary, secondary, and three-dimensional structure of GSTP1. Results: Our results showed that rs1695 polymorphism was not associated with the risk of oral cancer in any seven genetic models (G vs. A: OR= 0.9331, 95%CI= 0.6339-1.3737, P= 0.726; GG vs. GA+AA: OR= 0.9112 , 95%CI= 0.6865-1.2093, P= 0.520; GG+GA vs. AA: OR= 0.9006, 95%CI= 0.5522-1.4690, P= 0.675; GA vs. GG+AA: OR= 0.8732, 95%CI= 0.5763-1.3230, P= 0.522; GG vs. AA: OR= 0.9516, 95%CI= 0.5503-1.6456, P= 0.859; GG vs. GA: OR= 1.0645, 95%CI= 0.7891-1.4359, P= 0.683; GA vs. AA: OR= 0.8825, 95%CI= 0.5499-1.4162, P= 0.604). Also, we did not observe any significant associations in ethnicity-based stratified analyses. But bioinformatics studies have shown that this polymorphism can alter the physicochemical properties and secondary structure of the protein. Conclusions: Based on results, the rs1695 polymorphism could not be considered a risk factor for oral cancer.     

Tumor Necrosis Factor-α 238 G/A Polymorphism and Risk of Hepatocellular Carcinoma: Evidence from a Meta-analysis

Background: Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progressionof cancer. Many epidemiological studies have evaluated associations between the TNF-α 238 G/A polymorphismand hepatocellular carcinoma (HCC) risk, but the published data are inconclusive. Therefore, we performed thepresent meta-analysis. Methods: Electronic searches of several databases were conducted for all publicationson the association between TNF-α 238 G/A polymorphism and HCC through July 2012. Asummary odds ratio(OR) with its 95% confidence interval (CI) were calculated to evaluate the strength of this association. Results:Eleven case-control studies with a total of 1,572 HCC cases and 1,875 controls were finally included in thismeta-analysis. Overall, the TNF-α 238 G/A polymorphism was significantly associated with increased risk ofhepatocellular carcinoma in three genetic comparison models (For A versus G: OR 1.32, 95%CI 1.04-1.69, P =0.02, I2 = 40%; for AG versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.03, I2 = 40%; for AA/AG versus GG: OR1.33, 95%CI 1.03-1.72, P = 0.03, I2 = 41%) when all studies were pooled. Subgroup analysis by ethnicity furthershowed that there was a significant association between the TNF-α 238 G/A polymorphism and risk of HCC inAsians under three genetic comparison models (For A versus G: OR 1.30, 95%CI 1.00-1.68, P = 0.05, I2 = 45%for AA/AG versus GG: OR 1.31, 95%CI 1.00-1.71, P = 0.05, I2 = 46%). Conclusions: This meta-analysis providedconvincing evidence that the TNF-α 238 G/A polymorphism is associated with increased susceptibility to HCC.However, more well-designed studies with large sample size are needed to validate this association in Caucasians.     

TOX3基因单核苷酸多态与中国北方汉族绝经前妇女乳腺癌风险关联的研究

目的:探讨TOX3基因单核苷酸多态与中国北方汉族绝经前妇女乳腺癌风险的关系。方法:采用多重单碱基延伸单核苷酸多态性分型技术(Snapshot)分析方法,检测280例绝经前的乳腺癌患者和287例绝经前的正常对照者TOX3基因rs3803662和rs12443621多态性位点基因型,并比较不同基因型与乳腺癌风险的关系。结果:TOX3基因rs3803662和rs12443621多态性位点基因型频率,在乳腺癌病例组和对照组之间差异无统计学意义,P值分别为0.718和0.340。Logistic回归分析结果显示,对于rs3803662位点,与GG基因型相比,GA、AA和GA+AA基因型与乳腺癌的危险性无关(OR=0.846,95%CI:0.489～1.463,P=0.549;OR=0.802,95%CI:0.470～1.368,P=0.418;OR=0.821,95%CI:0.492～1.368,P=0.449);对于rs12443621位点,与GG基因型相比,GA、AA和GA+AA基因型与乳腺癌的危险性无关(OR=0.755,95%CI:0.518～1.099,P=0.755;OR=0.850,95%CI:0.528～1.368,P=0.504;OR=0.781,95%CI:0.548～1.112,P=0.170)。结论:在目前样本条件下,TOX3基因rs3803662和rs12443621位点多态性与中国北方汉族绝经前妇女乳腺癌易感性之间无明显关联。     

Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects

The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, no significant associations between the MTR A2756G polymorphism and breast cancer risk were found for GG versus AA (OR = 0.98, 95% CI: 0.84–1.15), AG versus AA (OR = 0.95, 95% CI: 0.89–1.01), GG/AG versus AA (OR = 0.95, 95% CI = 0.89–1.01), and GG versus AG/AA (OR = 1.00, 95% CI: 0.86–1.17). However, in the stratified analysis, significantly decreased breast cancer risks were found among Europeans (AG versus AA, OR = 0.90, 95% CI = 0.83–0.98; GG/AG versus AA, OR = 0.90, 95% CI = 0.82–0.97) and studies with population-based controls (AG versus AA, OR = 0.93, 95% CI = 0.86–1.00; GG/AG versus AA, OR = 0.93, 95% CI = 0.86–1.00). When stratifying by the menopausal status, no significant result was observed in all genetic models. Taken together, the results suggest that the MTR A2756G polymorphism may contribute to susceptibility to breast cancer among Europeans.