Cervical Cancer Susceptibility Research Articles

Genome-wide association study of cervical cancer suggests a role for ARRDC3 gene in human papillomavirus infection.

The development of cervical cancer is initiated by human papillomavirus (HPV) infection and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage and 1461 cases and 3295 controls in the follow-up stage. We identified novel-significant associations at 5q14 with the lead single nucleotide polymorphism (SNP) rs59661306 (P=2.4×10-11) and at 7p11 with the lead SNP rs7457728 (P=1.2×10-8). In 5q14, the chromatin region of the GWAS-significant SNPs was found to be in contact with the promoter of the ARRDC3 (arrestin domain-containing 3) gene. In our functional studies, ARRDC3 knockdown in HeLa cells caused significant reductions in both cell growth and susceptibility to HPV16 pseudovirion infection, suggesting that ARRDC3 is involved in the infectious entry of HPV into the cell. Our study advances the understanding of host genes that are responsible for cervical cancer susceptibility and guides future research on HPV infection and cancer development.

Replication of results from a cervical cancer genome-wide association study in Taiwanese women

Genetic epidemiological studies show that genetic factors contribute significantly to cervical cancer carcinogenesis. Several genome-wide association studies (GWAS) have revealed novel genetic variants associated with cervical cancer susceptibility. We aim to replicate 4 GWAS-identified single nucleotide polymorphisms (SNPs), which were associated with invasive cervical cancer in Chinese women, in a Taiwanese population. The rs13117307 C/T, rs8067378 A/G, rs4282438 G/T, and rs9277952 A/G SNPs were genotyped in 507 women with cervical squamous cell carcinoma (CSCC) and 432 age/sex matched healthy controls by using TaqMan PCR Assay. Human papillomavirus (HPV) DNA test and typing were performed in CSCC patients. Only the rs4282438 SNP was found to be significantly associated (G allele, odds ratio [OR] = 0.67, P = 1.5 × 10−5). This protective association remained in HPV-16 positive CSCC subgroup (G allele, OR = 0.60, P = 1.2 × 10−5). In conclusion, our study confirms the association of rs4282438 SNP with CSCC in a Taiwanese population. However, larger sample sets of other ethnic groups are required to confirm these findings.

Absence of toll-like receptor 9 Pro99Leu polymorphism in cervical cancer.

Background: Toll-like receptor 9 (TLR9) plays a key role in the elimination of viral pathogens by recognising their CpG DNA. Polymorphisms in the TLR9 gene may influence their recognition and subsequent elimination. Therefore, the present study was designed to elucidate the role of a rare unexplored TLR9 gene polymorphism C296T/ Pro99Leu (rs5743844) in cervical cancer susceptibility among Indian women. Methods: The genotyping of TLR9 Pro99Leu polymorphism in 110 cervical cancer patients and 141 healthy controls was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The genotype frequency detected in both cervical cancer and control populations was 1.0 (CC), 0.0 (CT) and 0.0 (TT); while the allele frequency was found to be 1.0 (C) and 0.0 (T). Conclusions: The present study demonstrates no involvement of TLR9 C296T/ Pro99Leu polymorphism in cervical cancer susceptibility and supports minor allele frequency (MAF) (0.0002) status of the same as no nucleotide variation was detected in any of the study subjects.

Genetic variants within 17q12 are associated with the risk of cervical cancer in the Han Chinese population

Chromosome 4q12 and 17q12 have been identified as two regions associated with susceptibility to cervical cancer in a genome-wide association study. To identify potential causal variants within these two regions, we conducted a case-control study including 1486 patients with cervical cancer and 1536 age-matched (±5 years) healthy controls. Based on RegulomeDB database, 12 potentially functional variants were selected and then genotyped by using Sequenom MassARRAY. Univariate and multivariate logistic regression models were used to evaluate the associations. We found that the G allele of rs8076131 and the A allele of rs12150079 in 17q12 region were significantly associated with increased risk of cervical cancer (adjusted OR = 1.15, 95% CI = 1.02–1.30, P = 0.02 for rs8076131; adjusted OR = 1.19, 95% CI = 1.03–1.36, P = 0.02 for rs12150079). Individuals with 3–4 risk alleles of these two variants had 24% higher odds of cervical cancer than those without the risk alleles (OR = 1.24, 95% CI = 1.07–1.44, P < 0.01). The stratified analysis showed that the associations of rs8076131 and rs12150079 with cervical cancer risk were statistically significant in subgroups of older menarche age (>16 years), more parities (≥2), nonsmokers, and having no family cancer history, but the test results for subgroup heterogeneity were not significant. The current study provides the evidence that rs8076131 and rs12150079 in 17q12 region may contribute to cervical cancer susceptibility in the Han Chinese population.

The Associations between Toll-Like Receptor 9 Gene Polymorphisms and Cervical Cancer Susceptibility

This meta-analysis systematically reviews the association between Toll-like receptor 9 polymorphisms and the risk of cervical cancer. Case-control studies focused on the association were collected from the PubMed, Web of Science, Cochrane Library, Embase, MEDLINE, CNKI, VIP, and Wanfang databases from inception to July 2017. We screened the studies and assessed the methodological quality of the included studies and extracted data. A meta-analysis was performed using RevMan 5.3 and Stata 12.0 software. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the associations between Toll-like receptor 9 polymorphisms and cervical cancer risk. A total of 9 studies comprising 3331 cervical cancer patients and 4109 healthy controls met the inclusion criteria. Of these, 8 studies contained information about G2848A (rs352140) and 4 studies contained information about −1486T/C (rs187084). Our results revealed that the associations between rs187084 and cervical cancer risk in the dominant model (p = 0.002) and heterozygous model (p = 0.002) were significant, with 1.30- and 1.32-fold increases in susceptibility, respectively, compared to that in the wild-type model. However, rs352140 was not related to cervical cancer regardless of whether the subgroup analysis was conducted (p > 0.05). In conclusion, there is a significant correlation between rs187084 and cervical cancer risk with the minor C allele increasing the risk of occurrence of cervical cancer. However, rs352140 is not associated with the occurrence of cervical cancer.

Absence of association between TLR4 Thr399Ile polymorphism and cervical cancer susceptibility

BackgroundToll-like receptors (TLRs) play a key role in pathogen detection and initiating inflammatory response. Several lines of evidence have suggested chronic inflammation as one of the major factors linked to carcinogenesis. Single nucleotide polymorphisms (SNPs) in TLR genes including TLR4 have been shown to be associated with cancer susceptibility, although reports have been conflicting. AimThe present case-control study was designed to ascertain the association of TLR4 C1196T/ Thr399Ile polymorphism with cervical cancer risk among Indian women. Patients and methodsThe study comprised of tumor biopsies from 110 histopathologically diagnosed cervical cancer cases and cervical smears from 141 disease free healthy controls. DNA was obtained using standard proteinase-K digestion and phenol-chloroform extraction method. Genotyping of samples was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. ResultsThe results showed presence of single genotype CC (Thr/Thr) and complete absence of T allele across all the sample types thereby showing genotypic frequency of 1.0, 0.0 and 0.0 for CC, CT and TT respectively in the study population. Patients aged >45 years showed association with late stages of cervical cancer. ConclusionComplete absence of T allele in our study subjects demonstrate no involvement of TLR4 Thr399Ile polymorphism in cervical cancer susceptibility. However, an association between increased age and late clinical staging was observed. A comprehensive analysis on a larger sample size covering diverse ethnic populations of India is warranted to comprehend the role of TLR4 Thr399Ile polymorphism.

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Human papillomavirus (HPV) is an essential but not a sufficient cervical cancer etiological factor. Cancer promoters, such as host genetic mutations, significantly modulate therapeutic responses and susceptibility. In cervical cancer, of interest have been viral clearing genes and HPV oncoprotein targets, for which conflicting data have been reported among different populations. This expert analysis evaluates cervical cancer genetic susceptibility biomarkers studied in African populations. Notably, the past decade has seen Africa as a hotbed of biomarker and precision medicine innovations, thus potentially informing worldwide biomarker development strategies. We conducted a critical literature search in PubMed/MEDLINE, Google Scholar, and Scopus databases for case-control studies reporting on cervical cancer genetic polymorphisms among Africans. We found that seven African countries conducted cervical cancer molecular epidemiology studies in one of Casp8, p53, CCR2, FASL, HLA, IL10, TGF-beta, and TNF-alpha genes. This analysis reveals a remarkable gap in cervical cancer molecular epidemiology among Africans, whereas cervical cancer continues to disproportionately have an impact on African populations. Genome-wide association, whole exome- and whole-genome sequencing studies confirmed the contribution of candidate genes in cervical cancer. With such advances and omics technologies, the role of genetic susceptibility biomarkers can be exploited to develop novel interventions to improve current screening, diagnostic and prognostic methods worldwide. Exploring these genetic variations is crucial because African populations are genetically diverse and some variants or their combined effects are yet to be discovered and translated into tangible clinical applications. Thus, translational medicine and flourishing system sciences in Africa warrant further emphasis in the coming decade.

Absence of toll-like receptor 9 Pro99Leu polymorphism in cervical cancer

Background: Toll-like receptor 9 (TLR9) plays a key role in the elimination of viral pathogens by recognising their CpG DNA. Polymorphisms in the TLR9 gene may influence their recognition and subsequent elimination. Therefore, the present study was designed to elucidate the role of a rare unexplored TLR9 gene polymorphism C296T/ Pro99Leu (rs5743844) in cervical cancer susceptibility among Indian women. Methods: The genotyping of TLR9 Pro99Leu polymorphism in 110 cervical cancer patients and 141 healthy controls was performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The genotype frequency detected in both cervical cancer and control populations was 1.0 (CC), 0.0 (CT) and 0.0 (TT); while the allele frequency was found to be 1.0 (C) and 0.0 (T). Conclusions: The present study demonstrates no involvement of TLR9 C296T/ Pro99Leu polymorphism in cervical cancer susceptibility and supports minor allele frequency (MAF) (0.0002) status of the same as no nucleotide variation was detected in any of the study subjects.

Significant association between IL10-1082/-819 and TNF-308 haplotypes and the susceptibility to cervical carcinogenesis in women infected by Human papillomavirus

Human papillomavirus (HPV) is responsible for high-grade cervical lesions and cervical cancer. The inflammation plays a key role in cervical cancer progression. In this context, studies propose an association between TNFα and IL10 SNPs and susceptibility to HPV infection. The present work aimed to investigate the possible association between IL10 and TNFα promoter polymorphisms and HPV infection in the cervical carcinogenesis risk in women from Brazil. A total of 654 samples was evaluated in this study. HPV detection was performed by PCR and HPV genotyping was performed by PCR and sequencing of positive MY09/11 PCR product. Genotyping of IL10 SNPs (rs1800871 and rs1800896) was performed by High Resolution Melt analysis. Genotyping of TNFα SNP (rs1800629) was performed by fluorogenic allele-specific probes. The distribution of TNF-308 (rs1800629) allelic (p = 0.03) and genotype (p = 0.03) frequencies and HPV-58 infection has showed a statistically significant difference between case and control groups for the assessed TNFα polymorphism. When it comes to TNFα (rs1800629) allelic and genotypic distribution and HPVs 18 and 31 infections, no statistically significant differences between case and control groups were observed for the studied TNFα polymorphism. The allelic and genotypic distribution of IL10-819 (rs1800871) and IL10-1082 (rs1800896) and HPV infection (HPVs 58, 18 and 31) has showed no statistically significant differences between case and control groups for the assessed IL10 polymorphisms. Furthermore, it was observed that haplotypes were associated with an increased cervical cancer risk in HPVs 16, 18 and 58-positive women. It was observed that women carrying the GTA and ATG haplotypes had 3.85 and 17.99-fold, respectively, increased cervical cancer susceptibility when infected by HPV-58. In women infected with HPV-16 and HPV-18, statistically significant results in women carrying the GTA and ATA haplotypes was observed. They had a 2.32 and 3.67-fold, respectively, increased cervical cancer susceptibility when infected by these two HPV types. The analysis of the haplotypes distribution in women infected with HPV-31 has showed no statistically significant results. Our study indicates that the association of genetic polymorphism in inflammation-related genes represents a risk to the susceptibility in the development of cervical cancer in women infected by HPVs 16, 18 and 58.

Absence of toll-like receptor 9 Pro99Leu polymorphism in cervical cancer.

Background: Toll-like receptor 9 (TLR9) plays a key role in the elimination of viral pathogens by recognising their CpG DNA. Polymorphisms in the TLR9 gene may influence their recognition and subsequent elimination. Therefore, the present study was designed to elucidate the role of a rare unexplored TLR9 gene polymorphism C296T/ Pro99Leu (rs5743844) in cervical cancer susceptibility among Indian women. Methods: The genotyping of TLR9 Pro99Leu polymorphism in 110 cervical cancer patients and 141 healthy controls was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The genotype frequency detected in both cervical cancer and control populations was 1.0 (CC), 0.0 (CT) and 0.0 (TT); while the allele frequency was found to be 1.0 (C) and 0.0 (T). Conclusions: The present study results demonstrate no involvement of TLR9 C296T/ Pro99Leu polymorphism in cervical cancer susceptibility and supports worldwide minor allele frequency (MAF) (0.0002) status of the same as no nucleotide variation was detected in any of the study participants.

E2F1 genetic variants and risk of cervical cancer in Indian women.

Altered expression of many E2F family members have been reported in various human cancers. In this study, we investigated the role of non-synonymous single nucleotide polymorphisms (rs3213172 C/T, rs3213173 C/T, and rs3213176 G/A) of the gene E2F1 with cervical cancer. A total of 181 samples including 90 cervical cancer patients and 91 healthy controls were genotyped. The genotype frequencies of these polymorphisms in collected samples were determined by either PCR-RFLP or PCR-ARFLP methods. SHEsis software was used to analyze the haplotypes. Statistically significant differences in the alleles and the genotypes frequencies were observed in rs3213172 (C/T) and rs3213173 (C/T) polymorphisms. The rs3213172 (C/T) polymorphism was a risk factor for cervical cancer in dominant model (odds ratio (OR) 1.96; 95% confidence interval (CI) 1.07, 3.60; P = 0.02) and heterozygous model (OR 1.90; 95% CI 1.01, 3.57; P = 0.04). The rs3213173 (C/T) polymorphism increased the risk of cervical cancer in the homozygous model (OR 2.71; 95% CI 1.11, 6.58; P = 0.02). The rs3213176 (G/A) polymorphism was not associated with cervical cancer risk in any of the genotypic models. In the haplotypes analysis, three haplotypes (CTG, TCG, and TTA) were associated with the cervical cancer risk. These findings revealed that rs3213172 (C/T) and rs3213173 (C/T) polymorphisms and haplotypes (CTG, TCG, and TTA) of the E2F1 gene might play role in the susceptibility of cervical cancer. This is the first report showing an association of these polymorphisms with the cervical cancer risk.

LINC00673 rs11655237 Polymorphism Is Associated With Increased Risk of Cervical Cancer in a Chinese Population.

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.

Association between FGFR4 gene polymorphism and high-risk HPV infection cervical cancer.

To discuss the association between FGFR4 gene polymorphism rs351855 (Glu388Aly) and the susceptibility and chemotherapeutic effect of cervical cancer infected by high-risk type HPV. A total of 162 patients with high-risk HPV cervical cancer and 162 healthy women were collected and the genotypes of the FGFR4 rs351855 locus were detected. The genotype distributions in the two groups were compared. The cervical cancer patients were divided into four groups which namely good therapeutic effect group and bad therapeutic effect, recurrence or metastasis and no recurrence or metastasis group respectively, and the risks of different genotype on the curative effect and prognosis were analyzed by Logistic regression. The survival time of patients with different genotypes was compared. There was no statistic difference in FGFR4 rs351855 genotype distribution between the patients group and control group (P>0.05), among which the risk of chemotherapy failure on GA+AA patients was 3.257 times as much as that of the GG patients, and the risk of recurrence or metastasis of GA+AA patients was 2.783 times as much as that of the GG patients. For AA patients, the risk of chemotherapy failure and the risk of relapse and metastasis are 3.833 and 3.406 times, respectively, as much as thatof the GG patients. The overall survival of GA and AA patients was shorter than that of the GG patients, and significant difference was found (χ2=7.098, P=0.029). The difference in overall survival between GA+AA patients and GG patients was almost statistically significant (χ2=3.634, P=0.057). The FGFR4 rs351855 polymorphism is not associated with the susceptibility of high-risk HPV cervical cancer, but patients with gene A was at higher risk of unfavorable chemotherapy prognosis compared with patients with GG.

HOTAIR rs7958904 polymorphism is associated with increased cervical cancer risk in a Chinese population

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.

Correlation between mutation of p53 gene 2-4 exons from peripheral blood and HPV16 positive cervical cancer susceptibility and clinical significance

Objective: To detect mutations of p53 gene 2-4 exons from peripheral blood and to explore their relevance in HPV16-positive cervical cancer susceptibility and clinical significance. Methods: Collected firstly cases from the Third Affiliated Hospital of Kunming Medical University from October 2012 to April 2014, included 167 cases HPV16-postive cervical cancer and 160 cases HPV-negative healthy women. Genomic DNA from the host peripheral venous blood was taken, mutations of p53 gene 2-4 exons were analyzed with software DNAstar after PCR and bidirectional sequencing. Meanwhile, mutations of p53 gene 2-4 exons among different clinicopathological characteristics in HPV16-postive cervical cancer were distinguished. Results: (1) Three mutations and an 16-bp insertion/deletion sequences were found in p53 gene exons 2-4, included C/G mutation of single nucleotide polymorphism (SNP) 11827 in intron2, A/C mutation of SNP11992 in intron3, C/G mutation in codon 72 (rs1042522) of exon4 and 16-bp (acctggagggctgggg) repeat insertion or deletion in intron3 (rs17878362), while deletion recorded as A1, insertion recorded as A2. No significant differences were found in each point allele and genotype frequency (P>0.05) . (2) Stratified analysis for cervical cancer group resulted with some differences. Compared group of non-squamous carcinoma with squamous carcinoma group, there were obviously decreased in allete A2 [11.8% (4/34) vs 3.5% (10/284) ; χ(2)=4.90, P=0.027], genotype A1A2 [4/17 vs 7.0% (10/142) ; χ(2)=5.14, P=0.023], and haplotype C-A2 [11.8% (4/34) vs 3.5% (10/284) ; χ(2)=4.91, P=0.027]. Compared with poorly differentiated group, allele C of SNP11827 and rs1042522 were obviously decreased in medium high differentiation group [50.8% (61/120) vs 38.8% (62/160) ; χ(2)=4.07, P=0.044], while haplotype G-A1 were apparently higher [49.2% (59/120) vs 61.2% (98/160) ; χ(2)=4.07, P=0.044], genotype GG of SNP11827 and rs1042522 were obviously decreased in superficial myometrial invasion depth group than that in deep myometrial invasion depth group [46.3% (25/54) vs 21.1% (8/38) ; χ(2)=7.06, P=0.029]. No significant differences were found between stage Ⅰ and Ⅱ, pelvic lymph node metastasis or not (all P>0.05) . Conclusions: No obvious correlation is found between polymorphisms in exons 2-4 of p53 gene and susceptibility of HPV16-postive cervical cancer. But the patient with allete C and A2, genotype GG and A1A2, haplotype C-A2 and G-A1 may be increase risk of poorly differentiation, deep muscular invasion and bad pathological type. Analysis of p53 gene polymorphism may be provide a basis for the prognosis evaluation and individualized treatment of cervical cancer.

Association of toll-like receptor gene polymorphisms and its interaction with HPV infection in determining the susceptibility of cervical cancer in Chinese Han population.

The aim of the study is to investigate the association of several single-nucleotide polymorphisms (SNPs) within Toll-like receptors (TLRs) gene and additional gene-gene and gene-human papillomavirus (HPV) infection interaction with cervical cancer risk. A total of 1262 participants are selected, including 420 cervical cancer patients and 842 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among five SNPs within TLR gene and HPV infection. Logistic regression was performed to calculate the ORs (95 %CI) for association of five SNPs within TLR gene and additional gene-HPV infection interaction with cervical cancer risk. Cervical cancer risk was significantly higher in carriers of the T allele of rs3775290 within TLR2 gene, the G allele of rs7873784 within TLR4 gene, and the A allele of rs352140 within TLR9 gene than those with wild genotype; adjusted ORs (95 %CI) were 1.78 (1.20-2.24), 1.65 (1.23-2.12), and 1.70 (1.16-2.31). However, we did not find any significant association of rs4986791 and rs11536889 with cervical cancer risk. GMDR analysis suggested a significant two-locus model (p = 0.0107) involving rs352140 and HPV infection. Subjects with HPV infection and rs352140-GA + AA genotype within TLR9 gene have the highest cervical cancer risk, compared to no HPV infection participants with rs352140-GG genotype, OR (95 %CI) = 3.22 (1.68-4.81). Pairwise LD analysis did not find any significant haplotype combination associated with cervical cancer risk. The minor alleles of TLR2-rs3775290, TLR4-rs7873784, and TLR9-rs352140, and interaction between rs352140 and HPV infection were all associated with increased cervical cancer risk.

Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the incidence of cervical cancer in Chhattisgarh

Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All subjects were genotyped for CYP1A1m1 (T>C) and m2 (A>G) using PCR-RFLP with statistical analysis by using SPSS version 16.0 and VassarStats (online). Among the two gene variants rs4646903 (T>C) and rs1048943 (A>G), individuals with AG and GG genotypes of CYP1A1m2 polymorphism have significantly higher and increased risk of cervical cancer (OR=2.0, 95%CI=1.04-3.84, p=0.035; OR=62.9, 95%CI=3.72-1063.83, p=0.004 respectively) and the association of CYP1A1m1 polymorphism did not show any significant relationship with cervical cancer patients (p=0.23). The ‘G’ allele showed strong association with the disease (p<0.0001). Thus, CYP1A1m2 polymorphism showed an increased risk in the population leading to cervical cancer. Our study suggested that the presence of ‘C’ allele of rs4646903 (T>C) showed no risk and ‘G’ allele of rs1048943 (A>G) might be a leading allele to cause increased cervical cancer susceptibility due to significant association of CYP1A1m2 gene polymorphism.

Correlation between polymorphisms in microRNA-regulated genes and cervical cancer susceptibility in a Xinjiang Uygur population.

We explored the correlation between single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer (CC) in a Xinjiang Uygur population. Ten SNPs in eight miRNA-regulated genes were selected for analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to detect correlations between SNPs and CC. We found that minor allele “C” of rs512715 in NEAT1 was associated with an increased risk of CC in the allele, codominant, dominant, overdominant and log-additive models. Minor allele “C” of rs4777498 in CELF6 was associated with an increased risk of CC in the recessive model. Minor allele “C” of rs3094 in RNASE4 was associated with increased risk of CC in the allele, dominant and log-additive models. In clinical stage III/IV CC patients, minor allele “C” of rs3094 in RNASE4 and minor allele “C” of rs8004334 in JDP2 were associated with increased risk. In subtype squamous carcinoma CC patients, minor allele “C” of rs512715 in NEAT1 and minor allele “C” of rs3094 in RNASE4 were associated with increased risk. In subtype adenocarcinoma CC patients, minor allele “C” of rs3094 in RNASE was associated with increased risk.

Prevalence and Associated Factors of Cervical Cancer Screening among Somali Women in an Urban Settlement in Kenya

Background: In Kenya, cervical cancer is ranked as the most frequent cancer among women with about 4,802 new cases being diagnosed and approximately 2,451 lives lost to it. Screening by Pap smear facilitates early detection, prompt treatment and consequently reduces mortality from cervical cancer. Though cervical screening services exist in Kenya, there is still high mortality rate due to cervical cancer. Objective: To determine prevalence and associated factors of cervical cancer screening among Somali women in Eastleigh, Nairobi, Kenya. Materials and methods: A cross-sectional study was conducted among 104 women selected by multi-stage sampling approach. The data was collected using pre-tested semi-structured questionnaire. Chi-square test (p<0.05) and odds ratio with corresponding 95% confidence interval were used to determine the association between screening and independent variables. Multivariate analysis was performed to determine predictors of cervical cancer screening. Conclusion: Based on our findings special emphasis should be directed at increasing awareness and perception about cervical screening as well as susceptibility of cervical cancer at all primary health care points through a welldesigned health education programme.

Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers. The present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility. The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and miRNA 196a2 polymorphisms showed no association with cervical cancer. However, interaction of miRNA polymorphisms with smoking habit showed higher risk of cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no significant modification in the risk of cervical cancer was seen for other polymorphisms. The results of the present study demonstrate that, miRNA 499 T/C polymorphism is significantly associated with genetic susceptibility to cervical cancer and may have a role in its pathogenesis.