PARP-1 Val762Ala polymorphism is associated with risk of cervical carcinoma.
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ABSTRACT:
SUBMITTER: Ye F
PROVIDER: S-EPMC3356257 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:BackgroundPoly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that plays a role in DNA repair, differentiation, proliferation, and cell death. The polymorphisms of PARP-1 have been associated with the risk of various carcinomas, including breast, lung, and prostate. We investigated whether PARP-1 polymorphisms are associated with the risk of non-Hodgkin lymphoma (NHL).MethodsSubjects from a Korean population consisting of 573 NHL patients and 721 controls were genotyped for 5 PARP-1 polymorphisms (Asp81Asp, Ala284Ala, Lys352Lys, IVS13+118A>G, and Val762Ala) using High Resolution Melting polymerase chain reaction (PCR) and an automatic sequencer.ResultsNone of the 5 polymorphisms were associated with overall risk for NHL. However, the Val762Ala polymorphism was associated with reduced risk for NHL in males [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.41-0.93 for CC genotype and OR, 0.84; 95% CI, 0.60-1.16 for TC genotype] with a trend toward a gene dose effect (p for trend, 0.02). The Asp81Asp (p for trend, 0.04) and Lys352Lys (p for trend, 0.03) polymorphisms revealed the same trend. In an association study of PARP-1 haplotypes, the haplotype-ACAAC was associated with decreased risk of NHL in males (OR, 0.75; 95% CI, 0.59-0.94).ConclusionThe present data suggest that Val762Ala, Asp81Asp, and Lys352Lys polymorphisms and the haplotype-ACAAC in PARP-1 are associated with reduced risk of NHL in Korean males.
| S-EPMC2843603 | biostudies-literature
Project description:Background and objectiveData on the Val762Ala (rs1136410) polymorphism in the poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP-1) gene as a risk factor for various types of cancers in different ethnicities are inconsistent. We studied this association in a Caucasian population.MethodsUsing high-resolution melting curve analysis (HRM), we studied the distribution of the PARP-1 Val762Ala polymorphism in patients with cervical cancer (n = 446) and in controls (n = 491).ResultsLogistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status demonstrated that the PARP-1 Val762Ala polymorphism was associated with an increased risk of cervical cancer. The adjusted odds ratio (OR) for patients with the Ala/Val genotype versus the Val/Val genotype was 1.381 (95 % CI = 1.025-1.859, p = 0.033), and the adjusted OR for the Ala/Ala or Ala/Val genotype versus the Val/Val genotype was 1.403 (95 % CI = 1.057-1.863, p = 0.019). The p value from the chi-square test of the trend observed for the PARP-1 Val762Ala polymorphism was statistically significant (p trend = 0.0123). Stratified analyses of the PARP-1 Val762Ala genotype distribution and cervical cancer risk showed that the age-adjusted OR of Ala/Ala or Ala/Val vs Val/Val for pregnancy was 1.388 (95 % CI = 1.027-1.877, p = 0.0328), 1.773 (95 % CI = 1.145-2.745, p = 0.0100) for contraceptive use, and 1.604 (95 % CI = 1.132-2.272, p = 0.0077) for postmenopausal women. The age-adjusted OR of Ala/Val vs Val/Val for contraceptive use was 1.769 (95 % CI = 1.114-2.809, p = 0.0154) and for postmenopausal women was 1.577 (95 % CI = 1.094-2.272, p = 0.0143).ConclusionOur studies suggest that the PARP-1 Val762Ala polymorphism may be a genetic risk factor for cervical cancer.
| S-EPMC3715681 | biostudies-literature
Project description:Previously, we have identified single nucleotide polymorphisms (SNPs) rs7958904 and rs4759314 in long non-coding RNA HOX transcript antisense RNA (HOTAIR) were significantly associated with risk of colorectal and gastric cancer, respectively. Here, we aimed to investigate the association between HOTAIR SNPs and cervical cancer (CC) susceptibility. A total of 1209 cases and 1348 controls were enrolled for association study and genotyped with TaqMan allelic discrimination method. The Cancer Genome Atlas (TCGA) database was utilized for in vivo analysis of allele-specific HOTAIR expression. MTT assay was employed for evaluation of allele-specific cell proliferation. The rs7958904 CC genotype was related to an increased risk of cervical cancer compared with the GG/GC genotypes (OR?=?1.57, 95% CI?=?1.10-2.25). TCGA database showed the CC tissues with rs7958904 CC genotype had higher HOTAIR expression than those with GG genotype (P?=?0.046). MTT assay demonstrated a growth-promoting role of rs7958904 C allele on CC cells. Further functional studies on the effect of rs7958904 on biological behavior of CC cells are needed to confirm and extend our findings. In conclusion, HOTAIR rs7958904 might influence CC susceptibility through modulation of CC cell proliferation, and could serve as a diagnostic biomarker.
| S-EPMC5466640 | biostudies-literature
Project description:The aim of this case-control study was to clarify the relationship between uracil N-glycosylase (UNG) rs3219218 and rs246079 genotypes and risk of cervical squamous cell cancer (CSCC). Modified polymerase chain reaction-mismatch amplification (MA-PCR) was applied for genotyping UNG rs3219218 (A/G) and UNG rs246079 (A/G) polymorphisms in 400 CSCC, 400 cervical intraepithelial neoplasia (CIN) III, and 1200 normal controls. We observed no association between the UNG rs3219218 (A/G) polymorphism and risk of CIN III or CSCC. However, risk of CIN III (odds ratio [OR]?=?1.58) and CSCC (OR?=?2.08) was significantly increased in cases with the homozygous GG genotype of UNG rs246079. At the UNG rs246079 (A/G) locus, individuals with the G allele or G carrier (GG?+?AG) genotype were at higher risk for CIN III (OR?=?1.34) and CSCC (OR?=?1.55). In the high-risk HPV (HR-HPV) positive group, homozygous GG of the UNG rs246079 genotype was associated with significantly increased risk of CSCC (OR?=?2.37) and CIN III (OR?=?1.81). Meanwhile, the proportion of G allele was significantly increased in CIN III (49.2%, OR?=?1.33) and CSCC (52.5%, OR?=?1.50) groups. G allele or G carrier (GG?+?AG) genotype was identified as a high-risk factor in CSCC (OR?=?1.67) while in the CIN III group, no major differences were evident relative to the control group (OR?=?1.45). A particularly high level of enrichment grouping was evident according to the number of sexual partners in the CIN III (P?=?.036) and CSCC (P?=?.001) groups. Our data clearly suggest an association between UNG rs246079 (A/G) and CSCC carcinogenesis, supporting the potential application of this polymorphism as a genetic biomarker for early prediction of cervical carcinoma.
| S-EPMC6319868 | biostudies-literature
Project description:Polymorphisms in pre-miRNAs may affect its expression, then having effect on its target mRNAs and be associated with cancer susceptibility. In the current study, we evaluated the association of a 3-base pair (3-bp) indel polymorphism (rs57408770) in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies. To further investigated the molecular mechanism underlying the correlation between rs57408770 and the risk of HCC, overexpression of pre-miR-3131 in HCC cell line was performed. Human HCC cell lines Sk-Hep-1 was obtained from Shanghai Cell Bank of Chinese Academy of Sciences on 9 December 2013.The fragment of 366bp including the insert allele of rs57408770 in pre-miR-3131 was directly synthesized and cloned into BamHI and EcoRI sites of pEGFP-N1 yielding the wild-type vector (pEGFP-N1-miR3131-WT). The mutant-type vector (pEGFP-N1-miR3131-MT) including the delete allele of rs57408770 was generated using QuikChange Lightening Site-Directed Mutagenesis Kit. The resulting constructs were verified by direct sequencing. For overexpression experiments, cells were cultured in 6-well plates at a density of 200 000 cells per well the day before transfection. 2.5μg plasmids of empty vector pEGFP-N1, pEGFP-N1-miR3131-WT or pEGFP-N1-miR3131-MT were transfected into the growing cells (about 80%-90% confluent) using Lipofectamine2000. After 24 hours of the transfection, the cells were collected for subsequent experiments.And human genome-wide gene expression profile assay was used to screen the targets of miR-3131.
2016-08-04 | GSE85123 | GEO
Project description:Cervical cancer is the fourth most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Few single-nucleotide polymorphisms associated with risk of cervical cancer have been identified, yet genetic predisposition contributes significantly to this malignancy. Long noncoding RNA LINC00673 has been widely explored for its role in the development and prognosis of many tumors, and 2 genome-wide association studies identified that LINC00673 rs11655237 was associated with susceptibility to pancreatic cancer. In the current study, using a case-control study design, we found rs11655237 significantly increased susceptibility of cervical cancer in a Chinese population (odds ratio = 1.27; 95% confidence interval = 1.08-1.50; P = .005). Expression of LINC00673 was significantly higher in adjacent normal tissues than in paired cancer tissues ( P < .01) and significantly lower in the cancer or paired adjacent normal tissues of patients with cervical cancer having rs11655237 allele A than in those having rs11655237 allele G ( P < .001). Our results indicate that LINC00673 rs11655237 is associated with increased risk of cervical cancer, possibly by downregulating LINC00673 expression in cervical tissues.
| S-EPMC6174653 | biostudies-literature
Project description:Polymorphisms in pre-miRNAs may affect its expression, then having effect on its target mRNAs and be associated with cancer susceptibility. In the current study, we evaluated the association of a 3-base pair (3-bp) indel polymorphism (rs57408770) in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies. To further investigated the molecular mechanism underlying the correlation between rs57408770 and the risk of HCC, overexpression of pre-miR-3131 in HCC cell line was performed. Human HCC cell lines Sk-Hep-1 was obtained from Shanghai Cell Bank of Chinese Academy of Sciences on 9 December 2013.The fragment of 366bp including the insert allele of rs57408770 in pre-miR-3131 was directly synthesized and cloned into BamHI and EcoRI sites of pEGFP-N1 yielding the wild-type vector (pEGFP-N1-miR3131-WT). The mutant-type vector (pEGFP-N1-miR3131-MT) including the delete allele of rs57408770 was generated using QuikChange Lightening Site-Directed Mutagenesis Kit. The resulting constructs were verified by direct sequencing. For overexpression experiments, cells were cultured in 6-well plates at a density of 200 000 cells per well the day before transfection. 2.5μg plasmids of empty vector pEGFP-N1, pEGFP-N1-miR3131-WT or pEGFP-N1-miR3131-MT were transfected into the growing cells (about 80%-90% confluent) using Lipofectamine2000. After 24 hours of the transfection, the cells were collected for subsequent experiments.And human genome-wide gene expression profile assay was used to screen the targets of miR-3131. For overexpression experiments, cells were cultured in 6-well plates at a density of 200 000 cells per well the day before transfection. 2.5μg plasmids of empty vector pEGFP-N1, pEGFP-N1-miR3131-WT or pEGFP-N1-miR3131-MT were transfected into the growing cells (about 80%-90% confluent) using Lipofectamine2000 (Invitrogen). After 24 hours of the transfection, the cells were collected for subsequent experiments. There are 3 samples in this experiment.
2016-08-04 | E-GEOD-85123 | biostudies-arrayexpress
Project description:Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability. Although single nucleotide polymorphisms (SNPs) in NBS1 have frequently been studied in multiple cancers, the relationships of two functional NBS1 polymorphisms (rs2735383 and rs1805794) with laryngeal carcinoma are yet unclear. Therefore, in the present study, we performed a case-control study including 342 cases and 345 controls to analyze the associations between two polymorphisms of NBS1 and the risk of laryngeal carcinoma.We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotypes of the functional SNPs in NBS1 gene.In comparison with the homozygous rs2735383GG genotype, the CC genotype was significantly associated with an increased risk of laryngeal carcinoma (adjusted OR?=?1.884, 95%CI?=?1.215-2.921). The rs2735383C variant genotypes (GC?+?CC) conferred a 1.410-fold increased risk of laryngeal carcinoma (adjusted OR?=?1.410, 95%CI?=?1.004-1.980). Furthermore, when compared to rs2735383GG genotype in laryngeal carcinoma tissues, the combined GC and CC genotypes exerted a significantly lower mRNA level of NBS1 (P?=?0.003). In contrast, no significant association was found between rs1805794G?>?C polymorphism and cancer risk (adjusted OR?=?1.074, 95%CI?=?0.759-1.518 for GC; adjusted OR?=?1.100, 95%CI?=?0.678-1.787 for CC; adjusted OR?=?1.079, 95%CI?=?0.774-1.505 for GC?+?CC).These findings indicate that rs2735383G?>?C polymorphism in NBS1 may play a crucial role in the development of laryngeal carcinoma.
| S-EPMC5810033 | biostudies-literature
Project description:Objective: Previous studies have reported that Ile462Val polymorphism in the gene Cytochrome P450 1A1 (CYP1A1) is associated with the risk of cervical cancer, but inconsistent results have emerged. Hence, we performed this updated and cumulative meta-analysis to ascertain a more accurate association between CYP1A1 Ile462Val polymorphism and risk of cervical cancer. Methods: Studies involving the CYP1A1 Ile462Val polymorphism associated with cervical cancer risk were searched from the databases of PubMed, Scopus, ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI). The strength of correlation was evaluated through calculating summary odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs). Subgroup analyses according to ethnicity, source of control and HWE were completed to further explore specific association between the polymorphism and the cancer risk. Results: Altogether, 11 eligible case-control studies were ultimately encompassed into the current meta-analysis, with 1,932 patients and 2,039 healthy controls. The total analysis revealed a borderline relationship between CYP1A1 Ile462Val polymorphism and cervical cancer risk in general population. Interestingly, after subgroup analyses based on ethnicity and source of control, the polymorphism increased the susceptibility of cervical cancer in Caucasian (G vs. A: OR = 1.97, 95% CI = 1.24-3.13; GG vs. AA: OR = 3 .24, 95% CI = 1.24-8.46; GA vs. AA: OR = 1.62, 95% CI = 1.25-2.10; GA+GG vs. AA: OR = 1.68, 95% CI = 1.16-2.43; GG vs. AA+GA: OR = 2.73, 95% CI = 1.05-7.10) and population-based (G vs. A: OR = 1.49, 95% CI = 1.10-2.02; GA vs. AA: OR = 1.41, 95% CI = 1.20-1.67; GA+GG vs. AA: OR = 1.40, 95% CI = 1.19-1.64) groups. Conclusion: The CYP1A1 Ile462Val polymorphism may enhance the susceptibility to cervical cancer in Caucasian females.
| S-EPMC5741838 | biostudies-literature
Project description:Host immunogenetic background plays an important role in human papillomavirus (HPV) infection and cervical cancer development. Inositol 1,4,5-triphosphate receptor type 3 (ITPR3) is essential for both immune activation and cancer pathogenesis. We aim to investigate if ITPR3 genetic polymorphisms are associated with the risk of cervical cancer in Taiwanese women. ITPR3 rs3748079 A/G and rs2229634 C/T polymorphisms were genotyped in a hospital-based study of 462 women with cervical squamous cell carcinoma (CSCC) and 921 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. No significant association of individual ITPR3 variants were found among controls, CSCC, and HPV-16 positive CSCC. However, we found a significant association of haplotype AT between CSCC and controls (OR = 2.28, 95% CI 1.31-3.97, P = 2.83 × 10-3) and the OR increased further in CSCC patients infected with HPV-16 (OR = 2.89, 95% CI 1.55-5.37, P = 4.54 × 10-4). The linkage disequilibrium analysis demonstrated that ITPR3 association with CSCC was independent of HLA-DRB1 alleles. In conclusion, these findings suggest that AT haplotype in the ITPR3 gene may serve as a potential marker for genetic susceptibility to CSCC.
| S-EPMC5354643 | biostudies-literature