Wild CC Genotype Research Articles

Study of the effect of ACYP2 single nucleotide polymorphisms rs843711 and rs843706 in Egyptian patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p> 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p>0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC.

Relationship of calcium-sensing receptor gene polymorphism CASR rs 1042636, CASR rs 1802757, and cinacalcet response among Egyptian hemodialysis patients with secondary hyperparathyroidism

Introduction: Secondary hyperparathyroidism (SHPT) is a common complication associated with morbidity and mortality among hemodialysis (HD) patients. Objectives: The current study aims to evaluate the frequency of CASR gene polymorphism variants related to parathyroid hormone (PTH) regulation (CASR rs1042636 and CASR rs1802757) and to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CASR gene alter the response to cinacalcet among Egyptian HD patients with SHPT. Patients and Methods: A case-control study that included 50 HD patients with intact parathyroid hormone (iPTH) ≥300 pg/mL treated with cinacalcet for a 6-month duration and 40 healthy volunteers as a control group. Eligible patients were recruited from Ain Shams university hospitals. Blood samples were collected from patients and controls to assess allele frequencies of CASR gene polymorphism variants using real-time polymerase chain reaction (PCR), corrected calcium (Ca), phosphorus (P), Ca×P product, iPTH level, and alkaline phosphatase before and after treatment. HD patients were categorized into two groups based on the reduction percentage; responders’ patients (iPTH ≥20%) and non-responders to cinacalcet treatment. Results: Of 50 HD patients, 48 (96%) carried the rs1042636 AA wild gene, while only two (4%) carried the rs1042636 AG mutant gene, 42 (87.5%) carried the rs1802757 CC wild genotype, and 6 (12.5%) carried the CT mutant genotype. The minor alleles T and G were (6.3% and 2%) respectively, with no statistically significant difference between the patient and control groups regarding the CASR genotypes or alleles distribution. There was no significant difference between responders and non-responder’s patient groups regarding CASR genotypes or allele frequencies. Moreover, no significant correlation between CASR genotypes or alleles to delta change of Ca, P, Ca×P product, or PTH was seen. However, CASR rs1802757 CT mutant genotype was associated with a significant reduction in alkaline phosphatase levels after treatment. Conclusion: There is no significant association between the gene polymorphism CASR rs1042636 or CASR rs1802757 and the reduction in PTH levels as a response to cinacalcet treatment among Egyptian HD patients with SHPT.

Relationship of DIO2 Gene with Productive Traits in Awassi Sheep in Thi-Qar Governorate

The research included 59 animals from the local Awassi sheep at the Sheep and Goats Research Station, in Al-Shatrah district, north of Thi Qar Governorate, Thi Qar Agriculture Directorate, from 20/10/2022 to 10/2/2023, to study the effect of the genotypes of the G>C.164 mutation on body dimensions and wool characteristics in local Awassi sheep. The study included measuring the characteristics of body dimensions (body length, front height, rear height, breast circumference and breast width), wool characteristics (staple length, fiber length and fiber diameter), by studying the nucleotide sequence (Sequencing) on the target genetic segment. The size of 350 base pairs was found to be located in exon 2 of the DIO2 gene in the local Awassi sheep sample. The presence of the C>G mutation at site 164, which is a missense mutation that changes the amino acid Proline (P) to Alanine (A), by calculating the allelic frequency, it was found that the C allele was significantly superior to the G allele in the G>C. 164 mutation, two genotypes (CC and CG) were found to have a significant correlation with most of the studied traits, except for fiber diameter. The highly significant superiority of the hybrid genotype CG in the G>C.164 mutant was observed in body length, front and hind height, breast circumference and breast width compared to the wild CC genotype. The wild genotype CC was significantly superior in staple length and fiber length in the same mutant.

DOES SLC11A2 GENE MUTATION ASSOCIATE WITH IRON-REFRACTORY IRON-DEFICIENCY ANEMIA AFTER BARIATRIC SURGERY?

ABSTRACT - BACKGROUND:After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered.AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB).METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism.RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%).CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.

PNPLA3/adiponutrin I148M gene variant in nonalcoholic fatty liver disease in Egyptian children and adolescents

Objective The aim was to explore the possible association of the PNPLA3/adiponutrin I148M gene variant with nonacholic fatty liver disease (NAFLD) and its severity in overweight and obese Egyptian children and adolescents as such reports are lacking in Egyptian population. Participants and methods In total, 80 overweight and obese NAFLD children and 40 healthy controls were subjected to clinical assessment, laboratory assessment, and genotyping assay for PNPLA3-I148M gene variant. Results There were no significant differences in the distribution of genotypes of the PNPLA3-I148M gene variant between the studied NAFLD patients and controls. In NAFLD children, 62 (77.5%) cases were CC genotype (homozygous for the wild allele), 12 (15%) cases were CG genotype (heterozygous for the risk allele), and six cases (7.5%) were GG genotype (homozygous for the risk allele). The frequency of the C allele (the common allele) was 85%, whereas the frequency of the G allele (the risk allele) was 15%. There was significant increase in mean values of alanine aminotransferase and gamma-glutamyl transferase (P<0.05) and significant increase in the frequency of patients with higher grades of steatosis among the NAFLD patients who were homozygous or heterozygous for the risk G allele (GG and CG genotypes) compared with those with no G allele (wild CC genotype). There were significant positive correlations between PNPLA3-I148M gene variant and obesity indicators among NAFLD children. Conclusions Polymorphisms in the PNPLA3-I148M gene variant may not contribute to NAFLD susceptibility in Egyptian children due to ethnic differences. However, the presence of polymorphisms in the PNPLA3-I148M gene variant may get worse in liver enzymes (alanine aminotransferase and gamma-glutamyl transferase) and grades of steatosis in NAFLD patients.

Association between hypoxia-inducible factor-1 alpha rs11549465 (1772 C>T) polymorphism and metabolic syndrome.

To find the association of single nucleotide polymorphism of hypoxia-inducible factor-1 alpha, rs11549465 (1772 Cytosine > Thymine) with metabolic syndrome, and to compare the anthropometric and biochemical variables in different genotypes of hypoxia-inducible factor-1 alpha. The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to April 2019, and comprised patients of metabolic syndrome selected from the Sheikh Zayed Hospital, Lahore. Healthy controls were also enrolled. Fasting venous sample was taken for the determination of study parameters. The genetic variant of hypoxia-inducible factor-1 alpha was analysed by restriction fragment length polymorphism polymerase chain reaction. Data was analysed using SPSS 22. Out of 400 subjects, 200(50%) each were patients and controls. The frequency of CC genotype of hypoxia-inducible factor-1 alpha Cytosine > Thymine in patients was 166(83%) and in controls 147(73.5%); CT genotype was 34(17%) and 53(26.5%) respectively, while TT genotype was not observed. There was a significant association of the C allele and CC genotype (p=0.03) with the increased risk of metabolic syndrome (p=0.02). On comparison of study variables in the two genotypes, systolic blood pressure, anthropometric and lipid parameters were significantly higher in the wild CC genotype compared to CT in the control group (p<0.05), but there was no significant difference in the patients (p>0.05). Major allele C of hypoxia-inducible factor-1 alpha 1772 Cytosine > Thymine was found to be associated with increased risk of metabolic syndrome.

Correlation between ZBRK1/ZNF350 gene polymorphism and breast cancer

BackgroundThis study is to explore the relationship between the ZBRK1/ZNF350 (Zinc finger and BRCA1-interacting protein with KRAB domain-1; also known as zinc-finger protein 350) gene polymorphism and early-onset breast cancer.MethodsThe ZBRK1/ZNF350 gene exon detection analysis was performed with the direct sequencing and Snapshot methods in 80 cases of breast cancer (aged ≤ 40 years old) and 240 healthy subjects (aged ≤ 40 years old).ResultsTotally 9 sequence variants were detected, including 5 missense mutations and 4 synonymous mutations, located at EXON3, EXON4 and EXON5, respectively. The rs4987241 and rs3764538 variants were published for the first time, while the remaining variants had been reported before. There were significant differences in the frequency distribution of family history between the breast cancer and control groups. Moreover, there were significant differences in the CT genotype frequency at the rs138898320 locus between the breast cancer and healthy control groups. Compared with the carriers of CC wild genotype at rs138898320, the risk of breast cancer was reduced by 88.3% in the CT mutant genotype carriers, with significant difference. In the stratification with no family history, compared with the carriers of CC wild genotype at rs138898320, significant differences were observed for the CT mutant genotype carriers. In the stratification with family history, there was no significant difference in the variation of rs138898320.ConclusionThe rs138898320 CT mutation genotype of ZBRK1/ZNF350 may reduce the risk of breast cancer, and the protecting effect would be increased in the stratification with no family history.Trial registration Not applicable.

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.

CD40 polymorphisms were associated with HCV infection susceptibility among Chinese population

BackgroundCD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population.MethodsThree single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis.ResultsAfter adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR = 1.368, 95%CI = 1.070-1.749, P = 0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR = 1.397, 95%CI = 1.078-1.809, P = 0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR = 1.337, 95%CI = 1.069-1.673, P = 0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR = 1.351, 95%CI = 1.060-1.702, P = 0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P > 0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P = 0.029, P = 0.047 and P<0.001, respectively).ConclusionsIn conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations.

Impact of CYP1A1, GSTP1 and XRCC1 genes polymorphisms on toxicity and response to chemotherapy in childhood acute lymphoblastic leukemia

BackgroundAcute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. Aim of the workThe aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL. Patients and methodologyNinety seven ALL pediatric patients were genotyped for CYP1A1, GSTP1 ILe105Val and XRCC1 Arg194Tryp single nucleotide polymorphisms (SNPs) using PCR-RFLP. ResultsNo statistically significant differences were observed between the wild and variant (homozygous and heterozygous) genotypes of the polymorphisms studied in CYP1A1, GSTP1 or XRCC1 genes regarding age, total leukocyte count, immunophenotyping, cytogenetic or risk group. The SNPs in CYP1A1, GSTP1 and XRCC1 genes did not show significant association with complete remission (CR) rate, overall survival (OS) or event free survival (EFS). However, XRCC1 Arg194Trp SNP was associated with higher drug toxicity; carriers of variant genotypes (CT and TT) had a significantly higher frequency of myelosuppression compared to those with the wild CC genotype (21/43[48.8%]) compared to (14/54[25.9%]) (p=0.020). The analysis of the combined effect of studied SNPs did not show any significant association with patient outcome. ConclusionOur study reported a significant association between the DNA repair gene polymorphism and myelosuppression in childhood ALL patients. Adjustment of the dose of chemotherapeutic agents according to XRCC1 Arg194Trp polymorphism may improve outcome in cases with risk of toxicity.

Association of PPP1R13L and CD3EAP polymorphisms with risk and survival of non-small cell lung cancer in Chinese non-smoking females

PPP1R13L and CD3EAP were confirmed to play important roles in transcription and apoptosis. SNPs in PPP1R13L and CD3EAP may be associated with lung cancer risk and survival. This study investigated the association of PPP1R13L rs1005165 and CD3EAP rs967591 with non-small cell lung cancer (NSCLC) risk and survival in Chinese non-smoking females. 442 NSCLC cases and 480 cancer-free controls were conducted in the case-control study, and 283 cases were in cohort study. Genotype was determined by Taqman real-time PCR. The statistical analyses were performed by SPSS 22.0 software. We found that rs1005165 and rs967591 were significantly associated with NSCLC risk in Chinese non-smoking females. For rs1005165, compared with homozygous wild CC genotype, carriers of CT or TT genotype had lower risk of NSCLC (adjusted ORs were 0.675 and 0.713, 95% CI were 0.461-0.988 and 0.525-0.968, respectively), adjusted OR for dominant model was 0.702, 95% CI was 0.526-0.937. For rs967591, AA genotype (adjusted OR = 0.721, 95% CI = 0.532-0.978) and at least one A allele (GA+AA) (adjusted OR = 0.716, 95% CI = 0.536-0.956) were significantly correlated with lower risk of NSCLC, compared with GG genotype. But we didn’t find correlation between the two SNPs and survival time in Chinese non-smoking NSCLC females. In general, we found PPP1R13L rs1005165 and CD3EAP rs967591 might be associated with lower NSCLC risk in Chinese non-smoking females, but no significant relationship was found with NSCLC survival.

Genetic polymorphisms in the TERT-CLPTM1L region and lung cancer susceptibility in Chinese males.

The objective of the present study was to analyze the relationship between genetic polymorphisms of the rs2736098 locus of the telomerase reverse transcriptase (TERT) gene and the rs401681 locus of the cleft lip and palate transmembrane protein 1 (CLPTM1L) gene and the risk of developing lung cancer in males in Jinzhou. A total of 214 lung cancer patients who were admitted in Jinzhou Medical University were analyzed, and 216 healthy males were selected as controls. Venous blood from all subjects and data on relevant risk factors were collected. DNA was extracted from peripheral blood by the phenol-chloroform method. Real-time fluorescent quantitative PCR (TaqMan real-time PCR) was used for DNA amplification. The genotyping results of the genetic polymorphisms of the TERT rs2736098 and CLPTM1L rs401681 loci were detected. The risk of developing lung cancer in the population with the TERT rs2736098 locus carrying the T allele was 1.614 times that with the TERT rs2736098 locus carrying the C allele after adjustment of the age factor. The risk of developing lung cancer in the population carrying the TT mutant genotype and the CT genotype increased significantly compared with that carrying the CC wild genotype [odds ratio (OR)=1.815, 95% CI=1.132–2.957; OR=2.417, 95% CI=1.158–4.943]. Based on a comparison between the combination of the two mutant genotypes (CT+TT) and the wild homozygous genotype (CC), the mutant genotype increased the risk of developing lung cancer (OR=1.955, 95% CI=1.213–3.157). The risk of developing lung cancer in the population with the CLPTM1L rs401681 locus carrying the T allele was 1.399 times that carrying the C allele (OR=1.343, 95% CI=1.035–1.978). The population with the TERT rs2736098 locus carrying the mutant genotype (CT+TT) was associated with the number of tumors (OR=0.553, 95% CI=0.236–0.928). In conclusion, in males, the TERT rs2736098 and CLPTM1L rs401681 T alleles are the susceptibility factors for developing lung cancer. Individuals, including the smoking population, who carry both the TERT rs2736098 and CLPTM1L rs401681 T alleles are more likely to develop lung cancer.

MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females.

This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3′UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.

Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population

BackgroundMicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer. MethodsThe genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age. ResultsFor miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59–0.99 and 0.46–0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients. ConclusionsThese findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.

The protective role of the −1306C&gt;T functional polymorphism in matrix metalloproteinase-2 gene is associated with cervical cancer: implication of human papillomavirus infection

Cervical cancer is the major reproductive health problem among women caused by persistent infection of high-risk human papillomavirus (HR-HPV). Metalloproteinase-2 (MMP-2) is an endopeptidase highly expressed in cervical cancer; however, the genetic link between aberrant expression of MMP-2 and cervical carcinogenesis is not known. The genotypic distribution, expression pattern of MMP-2 and HPV infection, was analyzed in a total of 300 fresh surgically resected cervical tissue biopsies. The MMP-2 C1306T (rs243865) promoter polymorphism dominant model (CC v/s CT + CT + TT) revealed that the CC genotype had a 4.33-fold significant increased risk for development of cervical cancer (OR = 4.33; 95% CI = 2.36-4.02, p = 0.0001) compared to those with variant genotypes (-1306 CT + TT). The C allele was associated with 3-fold significant increased risk (OR = 2.95; 95% CI = 1.90-4.60, p = 0.0002) compared to T allele. Interestingly, a significant correlation was found between high expression of MMP-2 protein and CC genotype in cancer patients (p = 0.001) compared to normal controls (p = 0.012). Further analysis showed that the risk of cancer was extremely pronounced in HPV positive patients (OR = 9.33; 95% CI = 2.88-30.20, p = 0.0001) compared to HPV negative ones, implicating the possible interaction between -1306CC genotype and HPV infection in increasing the cancer risk (p = 0.0001). The leads from the present study suggest the protective role of gene variant -1306C>T at the promoter region of the MMP-2 against HPV-mediated cervical cancer. These findings substantiate the functional role of MMP-2 C1306T polymorphism in a significant downregulation of MMP-2 protein in women with variant genotype (CT/TT) compared to the normal wild CC genotype.

The association between XRCC1 genetic polymorphisms and the risk of endometrial carcinoma in Chinese

Accumulated evidences report that X-ray repair cross-complementing group 1 gene (XRCC1) genetic polymorphisms play an important role in the development of endometrial carcinoma (EC). This study aims to evaluate the association of XRCC1 c.1161G>A and c.1804C>A genetic polymorphisms with the risk of EC. A total of 218 EC patients and 243 cancer-free controls were included in this study. The genotypes of XRCC1 genetic polymorphisms were determined by the created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. We found that these two genetic polymorphisms were statistically associated with the risk of EC. As for c.1161G>A, in comparison with GG wild genotype, the AA genotype was significantly associated with the increased risk of EC (OR=2.36, 95% CI 1.28–4.37, χ2=7.71, P=0.005). As for c.1804C>A, the CC genotype significantly increased the risk of EC in comparison with CC wild genotype (OR=2.77, 95% CI 1.38–5.58, χ2=8.54, P=0.003). Our data indicate that the A allele of c.1161G>A and c.1804C>A genetic polymorphisms could contribute to increase the risk of EC (for c.1161G>A: A versus (vs.) G, OR=1.34, 95% CI 1.02–1.76, χ2=4.56, P=0.033; for c.1804C>A: A vs. C, OR=1.34, 95% CI 1.01–1.77, χ2=4.03, P=0.045). Our results indicate that the XRCC1 c.1161G>A and c.1804C>A genetic polymorphisms significantly influenced the risk of EC in Chinese populations, and might be used as molecular markers for evaluating EC risk.

Association study of c.910A&gt;G and c.1686C&gt;G polymorphisms in XRCC1 gene with risk of hepatocellular carcinoma in the Chinese population

XRCC1 (human X-ray repair complementing defective repair in Chinese hamster cell 1) gene is considered a potentially important gene influencing the risk of hepatocellular carcinoma (HCC). Our analyses detected two allelic variants of XRCC1, c.910A>G and c.1686C>G. We aimed to investigate whether these polymorphisms influence the risk of HCC. The association between the XRCC1 polymorphisms and the risk of HCC was analyzed in 719 patients and 662 controls by polymerase chain reaction-restriction fragment length polymorphism. Our data suggested that the genotypes and alleles of c.910A>G and c.1686C>G polymorphisms were statistically associated with the risk of HCC. For c.910A>G, the GG genotype was associated with increased risk of developing HCC compared with the AA wild genotype (OR = 1.95, 95%CI = 1.40-2.70, P < 0.0001). For c.1686C>G, the risk of HCC was significantly higher for the GG genotype compared with the CC wild genotype (OR = 1.89, 95%CI = 1.375-2.599, P < 0.0001). Significant differences in the risk of HCC were also found with other genetic models for these two SNPs. The G allele of both c.910A>G and c.1686C>G may contribute to the risk of HCC (G versus A: OR = 1.40, 95%CI = 1.20-1.64, P < 0.0001 and G versus C: OR = 1.38, 95%CI = 1.19-1.61, P < 0.0001, respectively). Our findings suggest that the c.910A>G and c.1686C>G polymorphisms of XRCC1 are associated with the risk of HCC in the Chinese population.

Haplotype-based case–control study of DNA repair gene XRCC3 and hepatocellular carcinoma risk in a Chinese population

Previous studies indicated that the human X-ray repair complementing group 3 gene (XRCC3) plays an important role in hepatocellular carcinoma (HCC) susceptibility. We aimed to investigate the association of XRCC3 genetic polymorphism with HCC risk. This study was conducted in a Chinese Han population consisting of 300 HCC cases and 300 sex- and age-matched cancer-free controls. Three genetic variants (rs861539, rs12432907, and rs861537) were genotyped by the TaqMan® SNP Genotyping Assay. Our findings suggested that the TT genotype and T allele from rs861539 genetic variants were statistically associated with HCC risk. The TT genotype was statistically associated with the increased risk of HCC compared to CC wild genotype (P < 0.001). And the T allele was more common in the HCC patients than that in the control subjects. (OR = 1.97, 95% confidence interval (CI) 1.457 ~ 2.659, P < 0.001). Haplotype-based case-control study analysis indicated that TTG haplotype was more frequent in HCC groups than in the control group (odds ratio (OR) = 1.967, 95% CI 1.456 ~ 2.658); however, the CTG haplotype is more common in the control group than that in the HCC group (OR = 0.550, 95 % CI 0.430 ~ 0.703; P < 0.001). Our data indicated that genetic variants of the XRCC3 gene were statistically associated with HCC risk in a Chinese population.

TP63 Gene Polymorphisms, Cooking Oil Fume Exposure and Risk of Lung Adenocarcinoma in Chinese Non-smoking Females

Genetic polymorphisms of TP63 have been suggested to influence susceptibility to lung adenocarcinoma development in East Asian populations. This study aimed to investigate the relationship between common polymorphisms in the TP63 gene and the risk of lung adenocarcinoma, as well as interactions of the polymorphisms with environmental risk factors in Chinese non-smoking females. A case-control study of 260 cases and 318 controls was conducted. Data concerning demographic and risk factors were obtained for each subject. The genetic polymorphisms were determined by Taqman real-time PCR and statistical analyses were performed using SPSS software. For 10937405, carriers of the CT genotype or at least one T allele (CT/TT) had lower risks of lung adenocarcinoma compared with the homozygous wild CC genotype in Chinese nonsmoking females (adjusted ORs were 0.68 and 0.69, 95%CIs were 0.48-0.97 and 0.50-0.97, P values were 0.033 and 0.030, respectively). Allele comparison showed that the T allele of rs10937405 was associated with a decreased risk of lung adenocarcinoma with an OR of 0.78 (95%CI=0.60-1.01, P=0.059). Our results showed that exposure to cooking oil fumes was associated with increased risk of lung adenocarcinoma in Chinese nonsmoking females (adjusted OR=1.58, 95%CI=1.11-2.25, P=0.011). However, we did not observe a significant interaction of cooking oil fumes and TP63 polymorphisms. TP63 polymorphism might be a genetic susceptibility factor for lung adenocarcinoma in Chinese non-smoking females, but no significant interaction was found with cooking oil fume exposure.

Matrix metalloproteinase-2 C(-1306)T promoter polymorphism and breast cancer risk in the Saudi population.

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), displayed a strikingly lower promoter activity with the T allele. In the present study, we investigate whether this MMP-2 SNP is associated with susceptibility to breast cancer in the Saudi population. Ninety breast cancer patients and 92 age matched controls were included in this study. TaqMan Allele Discrimination assay and DNA sequencing techniques were used for genotyping. The results showed that, the frequency of MMP-2 CC wild genotype was lower in breast cancer patients when compared with healthy controls (0.65 versus 0.79). The homozygous CC (OR=2, χ(2)=5.36, p=0.02) and heterozygous CT (OR=1.98, χ(2)=4.1, p=0.04) showing significantly high risk of breast cancer in the investigated group. In conclusion our data suggest that the MMP-2 C(-1306)T polymorphism may be associated with increased breast cancer risk in the Saudi population.