Association between EGFR polymorphisms and the risk of lung cancer

Target: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. Methods: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by χ² test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). Results: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). Conclusions: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer.     

Correlation between the interactions of ABCA4 polymorphisms and smoking with the susceptibility to age-related macular degeneration

Objective: Our study was aimed to analyze the relationship between retina-specific ATP-binding cassette, sub-family A, member 4 (ABCA4) gene polymorphisms and gene-environment interactions with age-related macular degeneration (AMD) susceptibility. Methods: 98 AMD patients and 110 healthy controls, matched in age and sex, were enrolled in this study. ABCA4 polymorphisms (2633C>A, 5646G>A and 6389T>A) were determined by direct sequencing. Differences of genotype and allele distributions were analyzed by χ² test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were adopted to represent the relative risk of AMD. Gene-environment interactions were analyzed using crossover analysis. Results: 2633C>A polymorphism had no obvious correlation with AMD risk. Genotype AA and allele A in 5646G>A polymorphism significantly increased the risk of AMD (OR=4.753, 95% CI=1.249-18.085; OR=1.944, 95% CI=1.209-3.126). 6389T>A polymorphism AA genotype had no significant correlation with AMD risk, but the A allele distinctly enhanced the AMD risk (OR=1.681, 95% CI=1.071-2.639). Afterwards, we analyzed the interactions between ABCA4 polymorphisms and smoking on AMD. Smoking had interactions with all of 2633C>A (CC+CA), 5646G>A and 6389T>A polymorphisms, and the interactions were significantly correlated with AMD. Conclusions: 2633C>A (CC+CA) genotype, 5646G>A and 6389T>A polymorphisms of ABCA4 gene and smoking are susceptible factors for AMD, and the interactions of ABCA4 polymorphisms with smoking increased the risk of AMD.     

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.     

Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

Correlation between survivin genetic polymorphisms and lung cancer susceptibility

Aims: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. Results: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). Conclusions: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer.     

Association of MDR1 gene polymorphisms with the risk of hepatocellular carcinoma in the Chinese Han population

The multidrug resistance 1 gene (MDR1) is an important candidate gene for influencing susceptibility to hepatocellular carcinoma (HCC). The objective of the present study was to evaluate the association of MDR1 polymorphisms with the risk of HCC in the Chinese Han population. A total of 353 HCC patients and 335 healthy subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods were used to identify MDR1 gene polymorphisms. Two allelic variants (c.335T>C and c.3073A>C) were detected. The CC genotype of the c.335T>C polymorphism was associated with an increased risk of developing HCC compared to the TT genotype (OR = 2.161, 95%CI = 1.350-3.459, χ² = 10.55, P = 0.0011). The risk of HCC was significantly higher for the CC genotype in the c.3073A>C polymorphism compared to the AA genotype in the studied populations (CC vs AA: OR = 2.575, 95%CI = 1.646-4.028, χ² = 17.64, P < 0.0001). The C allele of the c.335T>C and c.3073A>C variants may contribute to the risk of HCC (C vs T of c.335T>C: OR = 1.512, 95%CI = 1.208-1.893, χ² = 13.07, P = 0.0003, and C vs A of c.3073A>C: OR = 1.646, 95%CI = 1.322-2.049, χ² = 20.03, P < 0.0001). The c.335T>C and c.3073A>C polymorphisms of the MDR1 gene were associated with the risk of occurrence of HCC in the Chinese Han population. Further investigations are needed to confirm these results in larger different populations.     

Association between COX-2 polymorphisms and non-small cell lung cancer susceptibility

Aim: To explore the association between COX-2 polymorphisms and non-small cell lung cancer (NSCLC) susceptibility. Methods: We collected fasting peripheral venous blood from 60 cases with NSCLC and 62 healthy controls through physical examinations, and applied PCR-RFLP to analyze COX-2 polymorphisms of two groups. Results: With respect to detecting COX-2 rs689466 and rs5275 polymorphisms, the distribution frequency of mutant genotype AA of COX-2 rs689466 in case group was higher than that in control group, which possessed significant difference between two groups (P < 0.05). Carriers with AA genotype were 4.05 times at risk of NSCLC than those with GG genotype (P = 0.04, OR=4.05, 95% CI = 1.14-14.43). The distribution of mutant genotype CC of COX-2 rs5275 was different between two groups, and carriers with genotype CC were at 5.70 times higher risk of NSCLC than those with genotype TT. After corrected by sex, gender, smoking and drinking factors, AA genotype of COX-2 rs689466 and CC genotype of COX-2 rs5275 still contributed to increased risk of NSCLC (OR=4.22, 95% CI=1.10-16.17, OR=6.95, 95% CI=1.27-38.11). After analyzed of linkage disequilibrium (LD) and haplotypes of alleles in two SNPs, the distribution frequency of A-C haplotype in case group was higher than that in control group, with significant difference between two groups (P < 0.05). After corrected by sex, gender, smoking and drinking factors, statistical difference was still found in the total distribution of A-C haplotype between two groups (P = 0.03, OR=6.11, 95% CI=1.16-32.2). Conclusions: COX-2 rs689466 and rs5275 polymorphisms may be related to NSCLC susceptibility. And A-C haplotype might be a susceptibility haplotype for NSCLC.     

Relationship between hWAPL polymorphisms and cervical cancer susceptibility

Purpose: To analyze the correlation of the polymorphisms of human wing-apart like (hWAPL) gene (rs7083506 and rs11202058) with the susceptibility to cervical cancer. Besides, the relationship of haplotypes between the polymorphisms with cervical cancer susceptibility was analyzed. Methods: Taqman probe genotyping method was adopted to detect the genotype distribution of hWAPL rs7083506 and rs11202058 polymorphisms in 117 cervical cancer patients and 128 healthy controls. Linkage disequilibrium and haplotypes were analyzed by Haploview software. χ² test was utilized to analyze the differences of genotype, allele and haplotype frequencies between the case and control groups. Results: Correlation analysis of hWAPL rs7083506 and rs11202058 polymorphisms with cervical cancer susceptibility was based on the five genetic models. TT genotype of rs7083506 increased the susceptibility of cervical cancer in TT vs. CC model and TT vs. CT+TT model (OR=2.249, 95% CI=1.018-4.970; OR=2.287, 95% CI=1.069-4.896). For rs11202058, the A allele increased the cervical cancer susceptibility (A vs. G, OR=1.502, 95% CI=1.005-2.245). No significant correlation was observed between rs11202058 genotypes and cervical cancer susceptibility. We performed the haplotype analysis between the two polymorphisms, and found that T-A haplotype significantly correlated with cervical cancer, the susceptibility of cervical cancer increased to 1.78 times. Conclusions: Rs7083506 and rs11202058 polymorphisms of hWAPL and their haplotype T-A were associated with cervical cancer.     

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.     

CX3CR1 polymorphisms and the risk of age-related macular degeneration

Background: Age-related macular degeneration (AMD), a most common eye disease, can lead to irreversible visual impairment. Age, genetic and environmental factors have been implicated in AMD. Chemokine (C-X3-C motif) receptor 1 (CX3CR1) gene polymorphisms could influence the susceptibility of AMD. Methods: We tested the association between AMD and single nocleotide polymorphisms (SNPs) of CX3CR1 gene (rs3732378 and rs3732379) in 102 cases and 115 controls from China. Genotypes were determined by MassArray genotyping assay method. Association between CX3CR1 gene polymorphisms and AMD were examined by χ² test and logistic regression. Results: Genotype distribution of CX3CR1 gene polymorphisms were in accordance with HWE examination. No obvious differences were observed in the genotypes of rs3732378 polymorphism between case and control groups (P>0.05), but A allele of it could increase the risk of AMD (P=0.025, OR=2.391, 95% CI=1.092-5.237). Both TT genotype and T allele of rs3732379 were significantly associated with the susceptibility of AMD (P=8.663, OR=8.663, 95% CI=1.044-71.874; P=0.021, OR=2.076, 95% CI=1.104-3.903). Age, gender and smoking status were used as common confounders to adjust the association between CX3CR1 gene polymorphism and AMD risk. Then we found that rs3732378 had no obvious association with AMD susceptibility. TT genotype of rs3732379 related to the occurrence of AMD, but the association was not significant (P=0.050, OR=8.274, 95% CI=1.002-69.963). T allele of rs3732379 might increase the susceptibility of AMD (P=0.029, OR=2.033, 95% CI=1.077-3.838). Conclusion: T allele of rs3732379 might have a positive association with the susceptibility of AMD.     

Association between ACE polymorphisms and osteoarthritis susceptibility

Objective: The present study was designed to investigate the association of angiotensin-converting enzyme (ACE) rs4343 and rs4362 polymorphisms with the susceptibility to osteoarthritis (OA). Methods: 109 knee OA patients and 114 healthy people were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to perform the genotyping for two groups and the linkage disequilibrium and haplotype were analyzed using Haploview software. The differences of genotype and allele frequencies were analyzed by χ² test and Fisher’s exact test. The relationship between ACE polymorphisms and OA susceptibility was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: The genotypes distributions of ACE rs4343 and rs4362 polymorphisms in control groups were accordance with HWE. ACE rs4343 polymorphism was associated with the significantly increased risk of OA (AG vs. AA: OR=2.41, P=0.003; GG vs. AA: OR=5.35, P=0.015; G vs. A: OR=2.27, P<0.001). Similarly, rs4362 polymorphisms was also a risk factor for OA (CT vs. CC: OR=2.60, P=0.005; TT vs. CC: OR=3.15, P=0.003; T vs. C: OR=1.88, P=0.001). The result of haplotype analysis showed complete linkage disequilibrium in rs 4343 and rs 4362 polymorphisms. The G-T haplotype significantly increased OA susceptibility, but A-C is a protective factor for the occurrence of OA. Conclusion: Significant correlation exists between ACE rs4343 and rs4362 polymorphisms and OA. In haplotype analysis, A-C haplotype may provide protection against OA, and G-T haplotype may be a risk factor for the development of OA.     

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.     

Association of ERCC gene polymorphism with osteosarcoma risk

BackgroundThe relationship between ERCC gene polymorphism and osteosarcoma risk / overall survival of osteosarcoma is still conflicting, and this meta-analysis was performed to assess these associations.Material and methodsThe association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method.ResultsFour studies were included for the association of ERCC gene polymorphism with osteosarcoma risk, and nine studies were recruited into this meta-analysis for the relationship between ERCC gene polymorphism and overall survival of osteosarcoma. The meta-analysis indicated that ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (A>G) gene polymorphism, ERCC2 rs13181 (Lys751Gln) gene polymorphism were not associated with osteosarcoma risk. ERCC1 rs2298881 (C>A) gene polymorphism, ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (Asp312Asn) gene polymorphism were not associated with overall survival of osteosarcoma. Interestingly, ERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma, but AA genotype not (A allele: OR = 0.78, 95% CI: 0.65–0.93, P = 0.007; GG genotype: OR = 1.32, 95% CI: 1.05–1.65, P = 0.02; AA genotype: OR = 0.69, 95% CI: 0.45–1.04, P = 0.08).ConclusionERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma.     

Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) rs10845498 Polymorphism Is Associated with a Decreased Risk of Non-Small Cell Lung Cancer

Objectives: Low-density lipoprotein receptor-related protein 6 (LRP6) modulates Wnt signaling transduction. Altered LRP6 expression leads to abnormal Wnt protein activation, cell proliferation and tumorigenesis. This study investigated the association between LRP6 single-nucleotide polymorphisms (SNPs) and non-small-cell lung cancer (NSCLC) in a Chinese population. Methods: A total of 500 NSCLC patients and 500 healthy controls were recruited for assessment of four LRP6 SNPs using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time of flight mass spectrometry. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Results: The frequency of the LRP6 rs10845498 genotype was 60.9% (A/A), 35.5% (AG) and 3.6% (GG) in patients with lung squamous cell carcinoma (SCC) and 69.2% (A/A), 27.2% (A/G) and 3.6% (GG) in controls. Logistic regression analysis revealed that the LRP6 rs10845498 A/A major allele was associated with a reduced risk in developing lung SCC (OR = 0.69; 95% CI, 0.48-1.00; P=0.04), and tobacco smokers had a 2.21 fold greater risk in developing SCC than nonsmokers (p<0.01, 95% CI, 1.72-2.85), and tobacco smokers who carried an “A” allele (AA+AG) in rs6488507 had a 2.34-fold greater risk in developing NSCLC than other patients (p< 0.01, 95%CI, 1.74-3.13). Conclusions: The LRP6 rs10845498 SNP is associated with a reduced risk of lung SCC, while tobacco smoke increases the risk. LRP6 rs6488507 polymorphism synergistically increased the risk of NSCLC in tobacco smokers. Further studies are needed to elucidate the functional impact of LRP6 expression and activity in NSCLC.     

Renal cell carcinoma risk is associated with the interactions of APOE,VHL and MTHFR gene polymorphisms

Objective: The study was designed to explore the association of renal cell carcinoma (RCC) with VHL (rs779805), MTHFR (rs1801133) and APOE (rs8106822 and rs405509) polymorphisms, investigate the interactions among the single nucleotide polymorphisms (SNPs), and explore roles of the interactions in the pathogenesis of RCC in Chinese Han population. Methods: 81 RCC patients and 80 healthy controls were included in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used in the analysis on the genotypes of APOE, VHL and MTHFR gene polymorphisms. Multifactor dimensionality reduction (MDR) method was adopted to conduct gene-gene interaction analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to evaluate the correlation between gene-gene interactions and RCC risk. Results: Significant correlations were found between RCC risk and 3 SNPs (rs8106822, rs779805 and rs1801133). Genotype AA and allele A of APOE rs8106822 were significantly associated with RCC susceptibility (OR=2.65, 95% CI=1.05-6.69). Meanwhile, we found that the frequencies of genotype GG and allele G were much higher in case group, compared with controls (P<0.05 for both) and they appeared to be risk factors for RCC (OR=2.90, 95% CI=1.22-6.87; OR=1.78, 95% CI=1.14-2.27). While, allele T of MTHFR rs1801133 could decrease the risk of RCC (OR=0.62, 95% CI=0.40-0.97). MDR analysis showed that gene-gene interactions among APOE, VHL and MTHFR SNPs were closely related with RCC susceptibility. Conclusion: APOE, VHL and MTHFR gene polymorphisms were related to the risk of RCC. The interactions among APOE, VHL and MTHFR genes could increase the risk of RCC.     

Association of the rs7395662 SNP in the MADD-FOLH1 and Several Environmental Factors with Serum Lipid Levels in the Mulao and Han Populations

Background: The rs7395662 single nucleotide polymorphism (SNP) in the MADD-FOLH1 has been associated with serum lipid traits, but the results are inconsistent in different populations. The present study was undertaken to investigate the association of rs7395662 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.Method: A total of 721 subjects of Mulao and 727 subjects of Han Chinese were randomly selected from our previous stratified randomized samples. Genotyping of the SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing.Results: Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.01). The allelic and genotypic frequencies in Han were different between males and females (P < 0.05 for each), but there was no difference between Mulao and Han or between Mulao males and females. The levels of low-density lipoprotein cholesterol (LDL-C) and ApoB in Mulao females were different among the genotypes (P < 0.05), the G allele carriers had higher LDL-C and ApoB levels than the G allele non-carriers. The levels of total cholesterol (TC), triglyceride (TG), LDL-C and ApoB in Han males and TC, TG and high-density lipoprotein cholesterol (HDL-C) in Han females were different among the genotypes (P < 0.05-0.01), the subjects with GG genotype in Han males had higher TC, TG, and ApoB and lower LDL-C levels than the subjects with AA or AG genotype, and the G allele carriers in Han females had lower TC and HDL-C levels than the G allele non-carriers. The levels of LDL-C and ApoB in Mulao females were correlated with the genotypes (P < 0.05 for each). The levels of HDL-C and ApoAI in Han males and HDL-C in Han females were correlated with genotypes (P < 0.05-0.001). Serum lipid parameters were also correlated with several environmental factors in both ethnic groups (P < 0.05-0.01).Conclusion: The association of rs7395662 SNP and serum lipid levels is different between the Mulao and Han populations, and between males and females in both ethnic groups.     

Association of PTEN gene polymorphisms with liver cancer risk

Objective: To find out if there are any relationship between three single nucleotide polymorphisms (SNPs) of phosphatase and tensin homolog (PTEN) gene (rs1234213, rs1234220, and rs2299939) and the susceptibility of liver cancer. Methods: Genotypes of the three SNPs in the PTEN gene were achieved utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Comparison of genotypes and alleles distribution differences between the case and the control subjects was accomplished with χ² test. The analysis of linkage disequilibrium (LD) and haplotypes of the three SNPs was performed using SHEsis software. We adopted odds ratios (ORs) with 95% confidence intervals (95% CIs) to show the relative risk of liver cancer. Results: TC genotype and C allele of rs1234220 polymorphism showed much more frequently in cases than in controls, reflecting that the TC genotype and the C allele may be linked to the increased risk of liver cancer (OR=2.225, 95% CI=1.178-4.204; OR=1.941, 95% CI=1.124-3.351). Rs2299939 polymorphism showed an opposite result that the GT genotype probably reduce the risk of liver cancer (OR=0.483, 95% CI=0.259-0.900). Statistical significance was not found in the distribution differences of the genotypes of rs1234213 between two groups. LD and haplotype analysis results of the three SNPs showed that the T-C-G haplotype frequency was much higher in cases than in healthy objects, which proved that the T-C-G haplotype might be a susceptibility haplotype for liver cancer (OR=3.750, 95% CI=1.396-10.077). Conclusions: PTEN gene polymorphisms might relate to liver cancer risk.     

The Association between GWAS-identified BARD1 Gene SNPs and Neuroblastoma Susceptibility in a Southern Chinese Population

A previous genome-wide association study (GWAS) has found that some common variations in the BARD1 gene were associated with neuroblastoma susceptibility especially for high-risk subjects, and the associations have been validated in Caucasians and African-Americans. However, the associations between BARD1 gene polymorphisms and neuroblastoma susceptibility have not been studied among Asians, not to mention Chinese subjects. In the present study, we investigated the association of three BARD1 polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) with neuroblastoma susceptibility in 201 neuroblastoma patients and 531 controls using TaqMan methodology. Overall, none of these polymorphisms was significantly associated with neuroblastoma susceptibility. However, stratified analysis showed a more profound association between neuroblastoma risk and rs6435862 TG/GG variant genotypes among older children (adjusted OR=1.55, 95% CI=1.04-2.31), and children with adrenal gland-originated disease (adjusted OR=2.94, 95% CI=1.40-6.18), or with ISSN clinical stages III+IV disease (adjusted OR=1.75, 95% CI=1.09-2.84). Similar results were observed for the variant genotypes of rs3768716 A>G polymorphism among these three subgroups. Our results suggest that the BARD1 rs6435862 T>G and rs3768716 A>G polymorphisms may contribute to increased susceptibility to neuroblastoma, especially for the subjects at age ≥12 months, with adrenal gland-originated or with late clinical stage neuroblastoma. These findings need further validation by prospective studies with larger sample size with subjects enrolled from multicenter, involving different ethnicities.     

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.     

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.