Cervical Cancer Susceptibility Research Articles

Genetic association of Interleukin-17A polymorphism in Bangladeshi patients with breast and cervical cancer: a case-control study with functional analysis

BackgroundBreast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer. MethodsThis case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases.ResultsFrom the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015).ConclusionOur study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.

Evaluation of the Association between Genetic Polymorphism of Interleukin-1 Beta (–511C/T and +3953C/T) and Cervical Cancer Susceptibility

Cervical cancer (CC) is the leading cause of cancer-related mortality among women, primarily caused by persistent human papillomavirus (HPV) infection, especially in developing countries. A proinflammatory cytokine, emerging as a major facilitator of carcinogenesis, is termed interleukin-1 beta (IL-1β), which characterizes host-environment interactions. Numerous epidemiological studies have revealed that IL-1β gene polymorphisms have been associated with numerous malignancies, but in the context of CC, results of these studies were inconclusive. Thus, our study aimed to explore the relationship between IL-1β polymorphisms (-511C/T and +3953C/T) and CC susceptibility. Genotyping was conducted on 192 CC patients and 200 healthy controls through polymerase chain reaction-restricted fragment length polymorphism. HPV analysis was done through real-time polymerase chain reaction, and the serum concentration of IL-1β was measured by enzyme-linked immunosorbent assay. Women with CT and TT genotypes of IL-1β -511C/T had a threefold increased risk of CC (odds ratio [OR], 3.60; 95% confidence interval [CI], 2.132-6.063; p < 0.001 vs. OR, 3.34; 95% CI, 1.952-5.713; p < 0.001) compared to controls. Women with the T allele of IL-1β -511C/T polymorphism were associated with increased CC susceptibility (OR, 2.00; 95% CI, 1.51-2.66; p = 0.0001) compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-1β +3953C/T polymorphism (OR, 0.93; 95% CI, 0.56-1.55; p = 0.86 vs. OR, 0.95; 95% CI, 0.72-1.26; p = 0.74). There was no significant association found between IL-1β -511C/T promoter (OR, 2.41; 95% CI, 0.46-12.76; p = 0.28 vs. OR, 1.64; 95% CI, 0.13-21.10; p = 0.7) and +3953C/T (OR, 3.76; 95% CI, 0.44-31.82; p = 0.19 vs. OR, 0.21; 95% CI, 0.01-3.92; p = 0.25) polymorphisms in tobacco chewers and smokers compared to controls. The level of serum concentration of IL-1β was significantly higher in cases compared to controls. Our results conclude that IL-1β -511C/T polymorphism is associated with CC susceptibility.

Association of HLA class I and II genes with cervical cancer susceptibility in a Han Chinese population.

Cervical cancer (CC) is one of the leading causes of cancer-related death in females worldwide. Genome-wide association studies (GWASs) have identified CC-related susceptibility loci in HLA regions. To investigate the associations between HLA genes and cervical intraepithelial neoplasia (CIN) or cervical cancer (CC), six loci of HLA class I (HLA-A, -B, and -C) and II (HLA-DRB1, -DPB1, and -DQB1) were selected for genotyping, and the associations between these alleles or their haplotypes with CIN or CC risk or protection from disease were evaluated. In total, 2193 participants, including 909 healthy individuals in the control group, 769 patients with CC, and 515 patients with CIN2+ (CIN II and III), were enrolled in the current study. HLA genes were genotyped using the NGSgo Illumina MiSeq workflow, and the associations between these loci and CIN2+ or CC at the allele and haplotype levels were analyzed. The allele frequencies of HLA-A*33:03, B*58:01, C*03:02, DPB1*05:01, and DRB1*12:01 were lower in both the CC and CIN2+ groups than in the control group, whereas those of B*55:02, C*04:03, and DPB1*03:01 were higher in the CC group than in the control group. In the histologic CC type analysis, the differences in the frequencies of these alleles in squamous cell carcinoma (SCC) of the cervix and stage I CC showed a consistent trend. In the haplotype analysis, the frequency of A*33:03-C*03:02-B*58:01 was lower in the CC and CIN2+ groups than in the control group, and that of A*24:02-C*04:03-B*15:25 was higher in the CC group than in both the control and CIN2+ groups. These three different haplotype frequencies were also identified in the FIGO CC stage analysis. In addition, in human papilloma virus (HPV) genotype analyses, the frequencies of HLA-C*03:02 and DPB1*05:01 were significantly lower in the CC and CIN2+ groups than in the control group, and in SCC subgroup, the frequencies of HLA-DQB1*04:01 and DRB1*04:05 were higher in the HPV other genotype infection group than in the HPV16 infection group. In both HPV16 single infection and coinfection with other HPVs, the frequency of haplotype A*33:03-C*03:02-B*58:01 was lower in both CC and CIN2+ than in the control group, while the frequencies of A*11:01-C*14:02-B*51:01 and A*24:02-C*03:04-B*13:01 were higher in the CIN2+ than in CC and the control group. In the HPV16 and other HPV infection comparisons, the frequencies of DRB1*04:05-DQB1*04:01-DPB1*02:01 and DRB1*11:01-DQB1*03:01-DPB1*05:01 were lower in the HPV16 infection group than in the other HPV infection group. Our results suggest that the HLA class I and II genes may affect the risk of CIN and CC as well as the histologic CC types and FIGO stages of CC in the Han Chinese population. In addition, HLA genes were associated with HPV16 infection at both the allelic and haplotype levels.

Vitamin D and Its Receptors in Cervical Cancer.

Several studies have investigated the relationship between vitamin D (VD) and its receptors (VDR) and the risk of cervical cancer. However, the underlying mechanisms that underpin these associations remain incompletely comprehended. In this review, we analyzed the impacts of VD and VDR on cervical cancer and related mechanisms, and discussed the effects of VD, calcium, and other vitamins on cervical cancer. Our literature research found that VD, VDR and their related signaling pathways played indispensable roles in the occurrence and progression of cervical cancer. Epidemiological studies have established associations between VD, VDR, and cervical cancer susceptibility. Current studies have shown that the inhibitory effect of VD and VDR on cervical cancer may be attributed to a variety of molecules and pathways, such as the EAG potassium channel, HCCR-1, estrogen and its receptor, p53, pRb, TNF-α, the PI3K/Akt pathway, and the Wnt/β-catenin pathway. This review also briefly discussed the association between VDR gene polymorphisms and cervical cancer, albeit a comprehensive elucidation of this relationship remains an ongoing research endeavor. Additionally, the potential ramifications of VD, calcium, and other vitamins on cervical cancer has been elucidated, yet further exploration into the precise mechanistic underpinnings of these potential effects is warranted. Therefore, we suggest that further studies should focus on explorations into the intricate interplay among diverse molecular pathways and entities, elucidation of the mechanistic underpinnings of VDR polymorphic loci changes in the context of HPV infection and VD, inquiries into the mechanisms of VD in conjunction with calcium and other vitamins, as well as investigations of the efficacy of VD supplementation or VDR agonists as part of cervical cancer treatment strategies in the clinical trials.

Role of rs2366152 single-nucleotide variant located in the long noncoding RNA HOTAIR gene in the cervical cancer susceptibility in a Polish population.

Previous studies have demonstrated an association of the NC_000012.12:g.53962605A > G, (rs2366152) single-nucleotide variant (SNV) situated in the long noncoding homeobox transcript antisense intergenic RNA (HOTAIR) gene with HPV16-related cervical cancer pathogenesis. However, little is known about the role of rs2366152 in cervical cancer progression and how oral birth control pills use, parity, menopausal status, and cigarette smoking influence the role of rs2366152 in cervical carcinogenesis. HRM analysis was used to determine the rs2366152 SNV prevalence in patients with cervical squamous cell carcinoma (SCC) (n = 470) and control group (n = 499) in a Polish Caucasian population. Logistic regression analyses were adjusted for age, using birth control pills, parity, menopausal status, and cigarette smoking. Our genetic studies revealed that the G/A vs. A/A (p = 0.031, p = 0.002) and G/A + G/G vs. A/A (p = 0.035, p = 0.003) genotypes of rs2366152 SNV were significantly related to the grade of differentiation G3 and tumor stage III, respectively. Moreover, cervical cancer risk increased among patients with rs2366152 SNV who smoked cigarettes and used birth control pills. We conclude that rs2366152 may promote the invasion and rapid growth of cervical SCC. Moreover, rs2366152 with cigarette smoking and using birth control pills can also be a risk factor for cervical cancerogenesis.

Telomerase reverse transcriptase gene polymorphisms and cervical cancer susceptibility in high-risk human papillomavirus-infected women.

To investigate the relationship between Human telomerase reverse transcriptase (hTERT) gene polymorphisms and the susceptibility and clinicopathological parameters of cervical cancer in women infected with high-risk human papillomavirus (HR-HPV). A total of 380 patients with HPV-infected cervical cancer who were admitted to the Jilin province Maternal and Child Health Care Hospital (Jilin province Obstetrics Quality Control Center) from July 2019 to July 2023 were selected as case group, and 408 women with negative HPV results in the cervical cancer screening results of the physical examination in the same hospital were selected as the control group. Restriction fragment length polymorphisms polymerase chain reaction was used to detect the polymorphisms of hTERT, and its relationship with the susceptibility to high-risk HPV infection and clinicopathological parameters in patients with cervical cancer was analysed. Individuals carrying the GA and AA genotypes of rs2736122 were significantly associated with an increased risk of cervical cancer when compared with the GG genotype and the adjusted ORs were 0.53 (0.37-0.79) for the AA genotype and 0.73 (0.59-0.88) for the A allele genotype. Besides, GG genotype or G allele of rs2853677 presented a significant influence on cervical cancer, with ORs of 0.59 (0.41-0.86) and 10.77 (0.63-0.94), respectively, when compared with the AA genotype. And rs2853677 have statistically significant difference in tumour diameter and degree of differentiation subgroup(p < 0.05). The results of this study indicate that the hTERT gene rs2736122AA and rs2853677 GG genotypes can increase the susceptibility of high-risk HPV infection in cervical cancer patients. And rs2853677 is related to tumours above 4 cm and highly differentiated tumours. But both have nothing to do with the patient's chemotherapy sensitivity.

Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis

BackgroundCervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. MethodsA total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. ResultsThe rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55–3.76, 1.81–12.45, 1.75–4.07, 1.39–9.35, 1.38–3.30, and 1.71–3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D’ = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. ConclusionOur case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

Polymorphisms of the interleukin-6 (IL-6) gene contribute to cervical cancer susceptibility in Bangladeshi women: A case-control study.

Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer-related deaths among females in Bangladesh. Interleukin-6 (IL-6) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single-nucleotide polymorphisms (SNPs) of IL-6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women. DNA was extracted from venous blood samples from cervical cancer patients (n = 126) and healthy controls (n = 120). Polymerase chain reaction-restriction fragment length polymorphismwas used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR)with 95% confidence interval (CI) and p values. We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55-5.07, p = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29-9.51, p = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76-12.81, p < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12-13.51, p = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer. Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL-6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women.

Abstract 766: A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women

Abstract Cervical cancer is the second most common female gynaecological malignancy in sub-Saharan Africa (SSA). Previous genome-wide association studies (GWASs) identified genetic variants associated with cervical cancer in women of European and Asian ancestry, particularly within the major histocompatibility complex (MHC). However, owing to the complexity of linkage disequilibrium and varied environmental exposures in different ancestral populations, regional GWASs are needed to investigate the genetic contribution to the pathogenesis of cervical cancer in continental African populations. A total of 1,637 cervical cancer patients and 761 controls in women of African ancestry were identified from the Johannesburg Cancer Study and the AWI-Gen study, respectively. DNA samples were genotyped on the 2.3 million H3Africa GWAS SNP array and genotyped SNPs imputed to a total of 13,937,308 SNPs. The association between genetic variants and cervical cancer was tested using linear mixed models, adjusting for five principal components and cryptic relatedness. We identified one locus within the MHC region associated with cervical cancer at genome-wide significance, led by rs3129965 (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.87-0.92, P = 2.292 x 10-11) near HLA-DRA. Four other loci were strongly associated with cervical cancer (P&amp;lt;5x10-7), including rs575105445 (OR=0.77, 95%CI=0.70-0.85, P = 2.188 x 10-07) near HLA-C,rs184053148 (OR =0.79, 95% CI = 0.72-0.86, P = 4.19 x 10-07) in TRIM31,rs12496921 (OR=0.88, 95%CI = 0.84-0.92, P = 1.32 x 10-07) in ROPN1B and rs114031308 (OR= 1.27, 95% CI =1.16-1.39, P =3.06 x 10-07) near TTC26. The genes in these loci are implicated in numerous pathways including antiviral immunity, DNA repair, the regulation of p53, apoptosis, cell growth and differentiation. These discoveries demonstrate the important contribution of common genetic variants to cervical cancer susceptibility and provide insights into its pathogenesis in women of African ancestry. Citation Format: Abram Bunya Kamiza, Wenlong Carl Chen, Jean-Tristan Brandenberg, Michele Ramsay, Christopher G. Mathew. A genome-wide association study identifies the association of common variants in the major histocompatibility complex with cervical cancer in black South African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 766.

Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis.

The clinical therapeutics of cervical cancer is limited due to the drug resistance and metastasis of tumor. As a novel target for antitumor therapy, ferroptosis is deemed to be more susceptible for those cancer cells with resistance to apoptosis and chemotherapy. Dihydroartemisinin (DHA), the primary active metabolites of artemisinin and its derivatives, has exhibited a variety of anticancer properties with low toxicity. However, the role of DHA and ferroptosis in cervical cancer remained unclear. Here, we showed that DHA could time-dependently and dose-dependently inhibit the proliferation of cervical cancer cells, which could be alleviated by the inhibitors of ferroptosis rather than apoptosis. Further investigation confirmed that DHA treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis. Among them, we unexpectedly found that heme oxygenase-1 (HO-1) played an antioxidant role in DHA-induced cell death. In addition, the results of synergy analysis showed that the combination of DHA and doxorubicin (DOX) emerged a highly synergistic lethal effect for cervical cancer cells, which was related also to ferroptosis. Overall, our data revealed the molecular mechanisms that DHA triggered ferritinophagy-dependent ferroptosis and sensitized to DOX in cervical cancer, which may provide novel avenues for future therapy development.

Genetic polymorphisms of CYP1A, CYP1B, CYP2C and risk of cervical cancer among rural population of Maharashtra: Findings from a hospital-based case-control study.

Last few decades, multiple studies all over the world revealed the association of genetic polymorphism in cytochrome P450 (CYP) genes with risk of developing different type of cancers, but contradictory outcomes were evidenced in case of cervical cancer (CC) risk. Therefore, the discrepancies in earlier reports influenced us to evaluate the association of CYP1A1*2A rs4646903, CYP1B1*3 rs1056836, CYP2C8*2 rs11572103, CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP2C19*2 rs4244285 polymorphisms and CC susceptibility in the women of rural population of Maharashtra. In this case-control study, genetic association of the polymorphisms in CYP genes was studied by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted among 350 clinically confirmed CC patients and 350 healthy volunteers in a population of south-western Maharashtra. The odds ratio (OR) with 95% confidence interval (CI) and P value were evaluated to get the level of association where P ≤ 0.005 was considered as statistically significant. After the analysis of single-nucleotide polymorphism (SNPs) of CYP1A1, CYP1B1, CYP2C8, CYP2C9, and CYP2C19, we noticed that CYP1B1*3 rs1056836 (Leu4326Val) polymorphism possessed a significantly elevated risk (OR = 3.28; 95% CI: 2.18-4.94; P < 0.0001), whereas CYP2C19*2 rs4244285 showed significantly lower risk (OR: 0.53, 95% CI: 0.33-0.85 P < 0.009) of CC in the studied rural population. The findings from this study supported that rs1056836 SNP of CYP1B1*3 increase CC development, whereas rs4244285 of CYP2C19*2 lowers the CC risk in the studied population.

HLA-G 3'UTR polymorphism diplotypes and soluble HLA-G plasma levels impact cervical cancer susceptibility and prognosis.

Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with relevance in several cancers. The aim of this study was to evaluate the potential role of soluble HLA-G (sHLA-G), its genetic polymorphisms and its haplotype structure in the susceptibility and prognosis of primary cervical cancer in a Chinese Han population. We investigated sHLA-G plasma levels and 3' untranslated region (3'UTR) polymorphisms through ELISA and direct DNA sequencing, respectively, in cervical cancer patients (120 cases) and healthy control women (96 cases). The data were analyzed for associations using PowerMarker, Haploview, and GraphPad Prism. In this study, 8 polymorphic sites, 16 haplotypes and 23 diplotypes in the HLA-G 3'UTR were identified in our study population. We observed that each pair of 8 polymorphic sites exhibited linkage disequilibrium. The heterozygote CT genotype at position +3422 (rs17875408) was more common in cervical cancer patients than in healthy women (OR=5.285, P<0.05). Haplotypes UTR-1, UTR-3, and UTR-7 accounted for more than 85% of both groups, but no significant difference was found. The frequency of the UTR-1/UTR-3 diplotype in patients was significantly higher than that in controls (P<0.05). In addition, we further observed that HLA-G 3'UTR polymorphisms may influence the sHLA-G plasma level in patients' peripheral blood, especially 14 bp Ins/Del (rs371194629) and +3142 C/G (rs1063320). A receiver operating characteristic (ROC) curve analysis showed that the sHLA-G level had good diagnostic performance in differentiating patients with cervical cancer from healthy women (AUC>0.7). Among patients, mean sHLA-G levels increased with increasing FIGO stages but were not related to the overall survival time. The results of the present study enhance our understanding of how HLA-G 3'UTR polymorphisms can influence the peripheral sHLA-G plasma level and play a key role in cervical carcinogenesis. This study further confirmed that sHLA-G may represent a novel plasma biomarker for the prognosis and potential therapeutic target of cervical cancer.

Association of ERCC1 rs11615 Polymorphism with the Risk of Cervical Cancer Especially in Chinese Populations: A Meta-Analysis.

Abnormalities of the ERCC1 gene can affect DNA repair pathways, thereby having a vital effect on genomic stability. A growing amount of case-control studies have focused on making an investigation of the association between ERCC1 rs11615 polymorphism and cervical cancer susceptibility. However, the controversial results have raised concerns. To draw a more accurate conclusion, six studies were elaborately selected from the electronic databases for this meta-analysis, with 753 cervical cancer cases and 851 healthy controls. We applied pooled ORs combined with 95% CIs to test the potential associations. Significant associations were revealed in Chinese populations (T vs C: OR = 1.557 and 95%CI = 1.234–1.966; TT vs CC: OR = 3.175 and 95%CI = 1.754–5.748; TT/CT vs CC: OR = 1.512 and 95%CI = 1.126–2,031; and TT vs CT/CC: OR = 2.836 and 95%CI = 1.592–5.051). Even when the studies deviating from HWE were excluded, an increased cervical cancer susceptibility was observed in Chinese. These results disclose that there is an obvious correlation between the risk of cervical cancer and ERCC1 rs11615 polymorphism, especially in Chinese populations, and the T variant is the risky one. Also, our findings need further studies to validate.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with cervical cancer in an Algerian population

Angiotensin-converting enzyme (ACE) has been reported to be associated with the pathogenesis and progression of human cancers. Nevertheless, the details of that role remain inconclusive. We conducted this case-control study to determine the frequency of the ACE I/D polymorphism and its relationship to the risk of cervical cancer in the Algerian population. Genotype analysis of the ACE I/D polymorphism was performed using polymerase chain reaction (PCR) in DNA isolated from peripheral blood samples of 88 cervical cancer patients and 161 healthy controls subjects. Overall, the frequencies of ID, II, and DD genotypes showed a significant difference between cervical cancer patients and controls (p &lt;0.0001). The I allele frequencies were more frequent in cervical cancer patients than in healthy subjects. Contrary to expectation, individuals’ carriers of the I allele (ID +II) had a significant increase in cervical cancer risk when using the genotype DD as the reference category (II+ID vs. DD: OR, 6; 95% CI, 2.71-13.29, p &lt;0.0001). Our results indicate that ACE I/D polymorphism may contribute to the development of cervical oncogenesis and might be used as a common risk factor for cervical cancer susceptibility.

Association of a genetic variant in the ATP-binding cassette sub-family B member 1 with risk of cervical cancer

BackgroundCervical cancer is one of the most prevalent cancers among women and is associated with high morbidity and mortality. Several factors are involved in the pathogenesis of cervical cancer including viral infections and/or genetic modifications that include single nucleotide polymorphisms (SNPs). MethodsWe aimed to investigate the association of genetic variants in ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs1128503) and Fc Gamma Receptor IIIa (FCGR3A) (rs396991) genes and susceptibility to cervical cancer in 263 individuals with or without this form of cancer. DNA samples were isolated and genotyped using a TaqMan based real-time (RT-) PCR method. ResultsThe rs1128503 was found to be associated with an increased risk of cervical cancer (recessive model: OR = 2.6, CI: 1.1–5.8, p = 0.02). whilst there was no association between the rs396991 and susceptibility to cervical cancer. ConclusionOur results showed that there is an association between the ABCB1 polymorphism and susceptibility for cervical cancer suggesting its potential as a risk stratification marker for cervical neoplasia.

CYP2D6 and CYP2E1 Gene Polymorphisms and their Association with Cervical Cancer Susceptibility: A Hospital Based Case-Control Study from South-Western Maharashtra.

In last few years several studies all over the world discovered the genetic polymorphisms in different cytochrome P450 genes associated with risk of various cancers, but contradictory outcomes were evidenced in case of cervical cancer risk. In this case-control study we aimed to see whether the polymorphism of CYP2D6 or CYP2E1 genes may or may not be associated with cervical cancer risk in women of rural Maharashtra. In this case-control study, the association of CYP2D6 and CYP2E1 gene polymorphism with cervical cancer risk was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted with 350 clinically confirmed cervical cancer patients and 350 healthy women in a population of South-Western Maharashtra. The Odds ratio (OR) with 95% confidence interval and p-value were evaluated, where p ≤0.005 was considered as statistically significant. After the analysis of SNP (rs389209) of CYP2D6 and SNPs (rs2031920, rs6413432, rs6413420) of CYP2E1, we noticed that variant allele A of CYP2E1*6 showed significant increase in cervical cancer cases (OR=4.81; 95% CI: 1.57- 14.77; p=0.005). The genotypic distribution of heterozygote G/A genotype of CYP2D6*4 showed negative association with cervical cancer development when age of cancer occurrence (OR=0.41; 95% CI: 0.27- 0.61; p<0.0001) and tobacco history (OR=0.35; 95% CI: 0.20- 0.59; p=0.0001) was considered. The findings from this study supported that rs6413432 SNP of CYP2E1*6 increased cervical cancer risk in the studied rural women population.

Association Between Potentially Functional Variants in chr5q14 and the Risk of Cervical Cancer in a Chinese Population.

Cervical cancer is a complex polygenic disease, and the interaction between single-nucleotide polymorphisms (SNPs) may lead to differences in the incidence and susceptibility of cervical cancer. In this study, we explored whether three potentially functional SNPs-rs59661306, rs257847, and rs637442 with reference/alternative alleles A/G, C/T, and T/G, respectively-in chr5q14 were related to cervical cancer risk in a Chinese population. A total of 703 samples were collected, including 215 patients with cervical cancer and 488 normal controls. The SNP genotyping was determined by using polymerase chain reaction-restriction fragment length polymorphism. There was an association between the AG rs59661306 genotype or the GG rs59661306 genotype and cervical cancer risk, and the percentage of cancer patients with the A/G rs59661306 genotype plus the percentage of cancer patients with the G/G rs59661306 genotype (AG + GG) was significantly higher than the percentage of AG + GG healthy women in the control group. There was no association between either the rs257847 or the rs637442 and cervical cancer risk. Genotype analysis showed that the genotype CT of rs257847 in combination with the AG, GG, and AG + GG genotypes of rs59661306 were associated with a higher cervical cancer risk, and that the genotypes TG and TG + GG of rs637442 in combination with the AG and AG + GG genotypes of rs59661306 were also associated with a higher cervical cancer risk. These findings indicate that rs59661306, rs257847, and rs637442 may be susceptible loci for cervical cancer. Our study advances the understanding of SNPs that are responsible for cervical cancer susceptibility.

Single Nucleotide Polymorphisms of EXOC1, BCL2, CCAT2, and CARD8 Genes and Susceptibility to Cervical Cancer in the Northern Chinese Han Population.

Cervical cancer (CC) is one of the main malignant tumors that threaten the health and lives of women around the world, and its morbidity and mortality rate ranks fourth. At present, most studies on the genetic background of CC focus on genetic polymorphisms. Single nucleotide polymorphisms (SNPs) are considered clinically as potential diagnostic and therapeutic biomarkers for a variety of tumors. Therefore, we aimed to explore the association between SNPs in different genes (EXOC1 gene, BCL2 gene, CCAT2 gene and CARD8 gene) and susceptibility to CC. This study is a case-control study based on women in northern Chinese, which included 492 women with CC and 510 healthy women. This study used multiplex PCR combined with next-generation sequencing to genotype the selected SNPs (rs13117307(C/T) in EXOC1 gene, rs2279115(C/A) in BCL2 gene, rs6983267(G/T) in CCAT2 gene and rs7248320(G/A) in CARD8 gene). The results of the study showed that there was no significant association between the four SNPs and the susceptibility to CC. However, in further stratified analysis, we found that rs13117307 and rs2279115 were significantly related to squamous cell carcinoma antigen (SCC-Ag) levels in women with CC, and rs6983267 was significantly related to the menopausal status of women with CC. Specifically, alleles T of rs13117307 and genoytpe AA of rs2279115 when SCC-Ag is greater than 1.5 ng/ml increase the risk of CC. The genotype TG/TG+TT of rs6983267 increases the risk of CC in premenopausal women. In conclusion, although we did not directly find a significant correlation between four SNPs, rs13117307 in EXOC1 gene,rs2279115 in BCL2 gene, rs6983267 in CCAT2 gene and rs7248320 in CARD8 gene, and CC susceptibility, we found that SNPs rs13117307, rs2279115, rs6983267 were associated with the clinical characteristics of several patients' CC patients. Therefore, this study provides us with new ideas for understanding CC and the diagnosis and treatment of CC in the future.

Encouraging HPV Vaccination via an Evolutionary Theoretical Approach: A Randomized Controlled Study in Japan.

In recent years, researchers have discussed the introduction of an evolutionary perspective into public health and health behavior research. We aimed to examine the effects of messages that target the fundamental human motive of kin care on HPV vaccination recommendations among mothers with daughters, based on an evolutionary theoretical approach. This study consisted of a three-arm parallel-group single-blinded randomized controlled study. A web-based survey was conducted from 7 to 8 October 2021 in Japan. Mothers with daughters (n = 969) were randomly assigned either to a group that received an intervention message that targeted the fundamental motive of kin care, or that targeted the fundamental motive of disease avoidance, or a control message. Intention to have daughter(s) receive HPV vaccination was assessed both before and right after reading the messages. A one-way ANOVA with Tukey’s or Games–Howell test was conducted. An intervention message targeting the fundamental motive of kin care and disease avoidance significantly increased intention of vaccination versus a control message (p < 0.001, respectively). There was no significant difference between the two intervention groups. The evolutionary theoretical approach that focuses on fundamental human motives may have the potential to extend the communication strategy for HPV vaccination recommendations. Health professionals may be recommended to deliver messages that target the fundamental motive of kin care as well as messages about the susceptibility and severity of cervical cancer and vaccine efficacy (e.g., “Getting cervical cancer can prevent childbirth. To protect your daughter and your future grandchildren, get your daughter vaccinated against HPV”). However, the present study only evaluated HPV vaccination intentions in Japanese mothers with daughters. Future studies should evaluate vaccination behavior in a wider range of subjects to confirm that the evolutionary theoretical approach promotes HPV vaccination.

Genetic Polymorphisms in microRNA Genes Targeting PI3K/Akt Signal Pathway Modulate Cervical Cancer Susceptibility in a Chinese Population.

Polymorphisms in microRNA (miRNA) genes could influence the expression of miRNAs that regulate the PI3K/Akt signalling pathway and play crucial roles in cancer susceptibility. To investigate the association of single nucleotide polymorphisms (SNPs) in miRNA genes of PI3K/Akt with cervical intraepithelial neoplasia (CIN) and cervical cancer (CC), nine SNPs located in miRNA genes were selected for genotyping, and the association of these SNPs with CIN and CC risk was evaluated. A total of 1,402 participants were enrolled in the current study, including 698 healthy individuals in the control group, 431 patients with CC, and 273 patients with CIN. Nine SNPs in miRNA genes (rs107822 in miR-219a, rs10877887 in let-7i, rs2292832 in miR-149, rs353293 in miR-143, rs3746444 in miR-499, rs3803808 in miR-132, rs4078756 in miR-10b, rs629367 in let-7a, and rs7372209 in miR-26a) were genotyped using MassArray, and the association of these SNPs with CIN and CC were analysed. The results showed that the frequencies of rs107822 in miR-219a and rs2292832 in miR-149 were significantly different between the control and CC groups (p < 0.005). The C allele of rs107822 in miR-219a was associated with an increased risk of CC (OR = 1.29, 95%CI:1.09–1.54) whereas the C allele of rs2292832 in miR-149 was associated with a decreased risk of CC (OR = 0.77, 95%CI:0.64–0.92). The results of inheritance model analysis showed that the best-fit inheritance models for rs107822 and rs2292832 were log-additive. The 2CC + CT genotype of rs107822 could be a risk factor for CC when compared with the TT genotype (OR = 1.28, 95%CI:1.08–1.51). The 2CC + CT genotype of rs2292832 could be a protective factor against CC when compared with the TT genotype (OR = 0.76, 95%CI:0.64–0.92). However, no association of these SNPs with CIN was found in the current study. Our results suggest that rs107822 in the promoter region of miR-219a and rs2292832 in pre-miR-149 region are associated with the risk of CC.