Wei-Bo Liang

RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies

Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5′ untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case–control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer.

Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

Background and Objectives Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. Methods In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. Results The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51). Conclusion These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.

A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer

Abstract The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34–0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64–0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43–0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.

Genetic polymorphism of interleukin-16 and risk of nasopharyngeal carcinoma.

BACKGROUND Common genetic variants in inflammatory cytokine genes can affect the risk of developing nasopharyngeal carcinoma (NPC). Interleukin-16 (IL-16), a pro-inflammatory cytokine, plays a pivotal role in inflammatory diseases as well as in the pathogenesis of tumors. METHODS We analyzed rs4778889 T/C, rs11556218 T/G, and rs4072111 C/T polymorphisms of IL-16 in 206 patients with NPC and 373 healthy controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing methods. RESULTS The rs11556218 T/G polymorphism of IL-16 gene was significantly associated with the susceptibility to NPC. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR=1.67; 95% CI, 1.18-2.36). Patients carrying the G allele had a significantly higher risk for developing NPC compared to individuals carrying the T allele (OR=1.36; 95% CI, 1.03-1.78). CONCLUSIONS This study shows an association between IL-16 gene polymorphisms and the risk of NPC, and our data suggests that IL-16 gene polymorphisms may be useful as genetic susceptibility markers for NPC.

Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis.

Early diagnosis of nasopharyngeal carcinoma (NPC) remains a challenge. Serum protein profiling is a promising approach for the classification of cancer versus noncancer samples. The objective of the current study was to assess the feasibility of mass spectrometry‐based protein profiling and a classification tree algorithm for discriminating between patients with NPC and noncancer controls.

The IL-16 gene polymorphisms and the risk of the systemic lupus erythematosus.

BACKGROUND Interleukin 16 (IL-16) is an immunomodulatory cytokine which plays an important role in many inflammatory and autoimmune diseases. We determined the association between SNPs of IL-16 gene (i.e. rs11556218 G/T, rs4778889 C/T, and rs4072111 C/T) and systemic lupus erythematosus (SLE). METHODS One hundred thirty-eight SLE patients and 199 controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing assay. RESULTS In the SLE group, the individuals carrying the G allele of rs11556218, the C allele of rs4778889 and the T allele of rs4072111 are at a significantly higher risk of SLE as compared with those carrying the T allele of rs11556218, the T allele of rs4778889, and the C allele of rs4072111 respectively (for rs11556218, OR=2.264, 95% CI, 1.64-3.127; for rs4778889, OR=1.927, 95%CI, 1.359-2.731; and for rs4072111, OR=2.417, 95% CI, 1.691-3.455). CONCLUSIONS The IL-16 gene polymorphisms may be associated with the risk of SLE.

CTLA4 and CD86 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) may be related to chronic inflammation and immune-mediated conditions, and its pathogenesis involves T-cell activation and proliferation. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecules (CD80/CD86) genes are important mediators of T-cell activation in the immune response. The aim of this study was to investigate whether +2379G/C (rs17281995) and +1057G/A (rs1129055) in CD86 and -318C/T (rs5742909) and +49A/G (rs231775) in CTLA-4 genes single nucleotide polymorphisms (SNPs) are associated with COPD in a Chinese population. The four polymorphisms were identified in 396 COPD patients and 400 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequency of the T allele of the -318C/T in CTLA-4 and the A allele of the +1057G/A in CD86 polymorphisms showed significant association with COPD when compared with controls (T allele: p < 0.0001; A allele: p = 0.009). Comparison of genotype frequencies showed that -318CT, +1057GA, and +1057AA genotype was overrepresented in the COPD group, respectively (-318CT: 50.8% vs 28.5%, p < 0.0001; +1057GA: 58.6% vs 54.2%, p = 0.002; +1057AA: 30.1% vs 25.8%, p = 0.002). However, we failed to find any association between the four SNPs and COPD when cases were classified by smoking status or clinical stages (p > 0.05). The results indicate that the polymorphisms of CTLA-4 (-318C/T) and CD86 (+1057G/A) may be important genetic factor associated with risk or protection for COPD in Chinese population.

Association of IL-1B Gene Polymorphisms with Nasopharyngeal Carcinoma in a Chinese Population

AIMS Interleukin-1beta (IL-1beta) is a multifunctional cytokine that up-regulates the inflammatory response and participates in carcinogenesis, malignant transformation, tumour growth, invasion and metastasis. The IL-1B gene, encoding IL-1beta cytokine, contains several single nucleotide polymorphisms. Previous studies have shown that the polymorphisms of this gene may be associated with an increased risk of some cancers. However, no specific genetic risk factor for nasopharyngeal carcinoma (NPC) has been identified so far and there is no report of the IL-1B gene polymorphisms in relation to NPC. The aim of this study was to test whether the promoter polymorphisms in the IL-1B gene are associated with the risk of NPC. MATERIALS AND METHODS Two single nucleotide polymorphisms of IL-1B gene (-511C/T and -31T/C) in 113 patients with NPC and 144 age- and sex-matched controls in a Chinese population were analysed using a polymerase chain reaction-restriction fragment length polymorphism strategy. RESULTS The IL-1B-31 and -511 loci were in highly linkage disequilibrium, and the -511T allele carriers were associated with a significantly increased risk of NPC as compared with the non-carriers (odds ratio=1.53, 95% confidence interval=1.07-2.17, P=0.018). Genotypes and allele frequencies at the IL-1B-31 locus in NPC cases were not different from the controls. Haplotype analysis showed that the -511T/-31T haplotype of the IL-1B gene conveyed the high risk for NPC compared with the -511C/-31T haplotype (odds ratio=17.09, 95% confidence interval=5.90-49.56, P<0.001). CONCLUSION This is the first report describing the association between IL-1B gene polymorphisms and NPC, and our data suggest that the IL-1B-511C/T polymorphism and the -511T/-31T haplotype may contribute to the risk of developing NPC in the Chinese population.

Population genetics for 17 Y-STR loci(AmpFISTR®Y-filerTM) in Luzhou Han ethnic group.

In this study, 17 Y-STR loci(AmpFISTR(®)Y-filerTM)-DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y-GATA H4, DYS437, DYS438, DYS448 were analyzed in 424 unrelated males from Luzhou Han ethnic group, Southwest China. 365 haplotypes were observed. The discrimination capacity was 0.8608 and the haplotype diversity was 0.9992.

Association between SNPs in pre-miRNA and risk of chronic obstructive pulmonary disease.

OBJECTIVES Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airway obstruction and persistent chronic airway inflammation and is influenced by genetic and environmental factors. This study aimed to explore the genetic aspect of its initial occurrence. DESIGN AND METHODS We conducted a case-control study of 432 COPD patients and 511 control subjects frequency-matched in age and gender distribution. We genotyped three single nucleotide polymorphisms (SNPs) in pre-miRNAs using a PCR-RFLP assay and evaluated their relevance to COPD susceptibility. RESULTS We found that the TT genotype and T allele of miR-196a2 rs11614913 were significantly associated with a decreased risk for COPD, compared with the CC genotype and C allele. Similarly, the GG genotype and G allele of miR-499 rs3746444 were associated with a decreased risk for COPD, compared with the AA genotype and A allele. CONCLUSIONS These findings suggest that both rs11614913 and rs3746444 may be involved in susceptibility to COPD.