CCND1 Rs9344 Research Articles

Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study.

Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

Association of CCND1 Gene Polymorphism rs9344 with Grade and Invasion Degree of Colorectal Cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital

The majority of colorectal cancer (CRC) are sporadic CRC that can be caused by genetic variations such as Single Nucleotide Polymorphisms (SNPs). The CCND1 gene polymorphism rs9344 could involve at the beginning and the development of CRC. This study aimed to analyze the association between CCND1 gene polymorphism rs9344 with the grade and invasion degree of colorectal cancer in at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali. This cross-sectional study was carried out at the Integrated Biomedical Laboratory Unit, Faculty of Medicine, Udayana University. Data analysis of 32 samples showed majority age was above 50 years old as many as 28 (87.5%), with men as 21 samples (65.6%). Histopathology description was adenocarcinoma in 32 samples (100%). Grading histopathology low grade was 31 samples (96.6%). The degree of tumor invasion was high as 25 samples (78.1%). From the aspect of pathological stage pNx as much as 27 (84.4%). The majority location of tumors was on the left side as 21 samples (65.6%). The polymorphisms of CCND1 rs9344 genotype sequentially AA as 20 samples (62.5%), AG as 9 samples (28.1%), while GG as 3 samples (9.4%). The statistical analysis found that CCND1 gene polymorphism rs9344 was not associated with colorectal cancer grade (p>0.05), and not associated with invasion degrees of colorectal cancer (p>0.05). Taken together, we conclude that no significant association between the CCND1 gene polymorphism rs9344 with grade and invasion degree of colorectal cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali.

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk.

Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI). Cochran's Q-test and I2 were used to study heterogeneity, based on which either a random or a fixed effect model was implemented. The meta-analysis identified 11 SNPs (from 10 genes) to be significantly associated with increased EC risk. Among these, seven SNPs were significant in at least three of the five genetic models, as well as three of the polymorphisms (rs1801320, rs11224561, and rs2279744) corresponding to RAD51, PGR, and MDM2 genes, which contained more than 1000 EC cases each and exhibited increased risk. The current meta-analysis indicates that polymorphisms associated with various hormone related genes-SULT1A1 (rs1042028), PGR (rs11224561), and CYP19A1 (rs10046 and rs4775936); DNA repair genes-ERCC2 (rs1799793), OGG1 (rs1052133), MLH1 (rs1800734), and RAD51 (rs1801320) as well as genes like MDM2 (rs2279744), CCND1 (rs9344), and SERPINE1 (rs1799889), are significantly associated with increased EC risk.

Significant Association of CCND1 Genotypes With Susceptibility to Childhood Acute Lymphoblastic Leukemia.

This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis.

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

Cyclin D1 and p21 gene variants and oral squamous cell carcinoma risk and prognosis

Cyclin-dependent kinase inhibitor p21 (encoded by the CDKN1A gene) and cyclin D1 (encoded by the CCND1 gene) are important regulators of cell cycle progression and could have important effects in the complex process of neoplastic transformation. The current study aimed to investigate variants in CDKN1A (rs1801270, rs1059234) and CCND1 (rs9344) genes as potential risk and prognostic factors in oral squamous cell carcinoma (OSCC) patients. The study included 104 OSCC patients and 107 healthy individuals without a history of cancer. Genotypes were assessed by real-time PCR and TaqMan SNP genotyping. Significant differences in genotype distribution between OSCC cases and the control group were observed for the CCND1 rs9344 variant (p=0.017). According to the odds ratio (OR), adjusted for age and sex, the rs9344 heterozygous GA and homozygous mutated AA genotypes were associated with an increased OSCC susceptibility (OR=2.295, p=0.007; OR=2.029, p=0.037, respectively). Variants rs1801270 and rs105923 in CDKN1A were not associated with OSCC risk. There were no differences in overall survival among OSCC patients stratified by genotypes of the analyzed variants in CDKN1A and CCND1. Variant rs9344 in the CCND1 gene might be considered as a potential molecular risk factor for OSCC susceptibility but not for disease prognosis.

Significant Association of Cyclin D1 Promoter Genotypes With Asthma Susceptibility in Taiwan.

The molecular mechanisms underlying the association between cell cycle and asthma are poorly understood, and cyclin D1 (CCND1) is found to be upregulated in asthma airway smooth muscle. We investigated whether the most frequently examined functional variants in CCND1 determine asthma susceptibility. We genotyped 651 participants for single-nucleotide polymorphisms (SNPs) at rs9344 and rs678653 on CCND1 and assessed the association of these SNPs with asthma risk. Significant differences were found in the distributions of genotypic (p=0.0064) and allelic (p=0.0021) frequencies of CCND1 rs9344. In addition, AG or GG carriers had 0.63- or 0.48-fold adjusted odds ratios for asthma risk (95%confidence intervals=0.48-0.92 and 0.22-0.78, respectively) than those who carried the AA wildtype. Our results suggest that cell cycle regulation may play a role in asthma initiation and development, and the CCND1 rs9344 genotype may serve as an early detection marker for asthma.

CCND1 Splice Variant as A Novel Diagnostic and Predictive Biomarker for Thyroid Cancer.

Cyclin D1 protein is aberrantly overexpressed in thyroid cancers, but mutations of the CCND1 gene are rare in these tumors. We investigated the CCND1 rs9344 (G870A) polymorphism and the expression profiles of wild-type CCND1a and shortened oncogenic isoform CCND1b at the mRNA and protein levels in 286 thyroid tumors. Genotype AA of rs9344 was associated with high expression of CCND1b mRNA and was more frequently found in thyroid cancer than in benign tumors. The mRNA expression levels of CCND1b were higher in papillary thyroid carcinoma (PTC) than in benign or other malignant tumors. However, the expression of CCND1a mRNA showed no association with the parameters. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was distinguished from PTC by low expression of CCND1b at mRNA and protein levels. We further observed that cyclin D1b immunostaining helped to avoid the misdiagnosis of classic PTC with predominant follicular pattern as NIFTP in a separate cohort. Nuclear cyclin D1b expression was associated with aggressive clinicopathologic features in PTC. These findings suggest that cyclin D1b overexpression can be used as a diagnostic and predictive biomarker in thyroid tumors and may be functionally involved in the development and progression of the disease.

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population.

Some studies investigated the association between CCND1 rs9344 polymorphism and hepatocellular carcinoma (HCC) risk. However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship. Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases. The strength of the association was calculated with the odds ratio (OR) and respective 95% confidence intervals (Cis). We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88-1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05-2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71-1.18). This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population

Genetic polymorphisms in cyclin D1 are associated with risk of renal cell cancer in the Chinese population.

Recently, the functional polymorphisms in Cyclin D1 (CCND1) have been shown the potential influence to risk of renal cell cancer (RCC). Therefore, the present study was performed to investigate whether these polymorphisms could influence the susceptibility of RCC. Four potentially functional polymorphisms in CCND1 (rs1944129, rs7177, rs9344 and rs678653) were genotyped in this hospital-based case-control study, comprising of 1,488 RCC patients and 1,677 cancer-free controls in a Chinese population by the TaqMan assay. The logistic regression was used to assess the associations between CCND1 polymorphisms and the risk of RCC. We found the genotype and allele frequency distribution of rs1944129 and rs7177 were significantly associated with risk of RCC (P = 0.015 and P = 0.018, respectively). The analysis of combined risk alleles revealed that patients with 2-4 risk alleles showed an elevated risk of RCC compared to those with 0-1 risk alleles (OR = 1.35, 95% CI = 1.15 - 1.58, P < 0.001). Furthermore, compared with the genotypes containing G allele (AG and GG), the patients carrying the AA genotype in CCND1 rs1944129 polymorphism had a significantly greater prevalence of high clinical stage disease (OR = 0.56, 95% CI = 0.33 - 0.94, P = 0.029). These results suggested that these CCND1 polymorphisms rs1944129 and rs7177 might contribute to the susceptibility of RCC in the Chinese population.

The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-kB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma.

Radiotherapy is one of the primary choices for the treatment of nasopharyngeal carcinoma (NPC) and may result in severe radiotoxicities on normal tissues. Single nucleotide polymorphisms (SNPs) in genes of cell cycle and NF-κB pathways have been linked with the prognoses of various cancers. The aim of this study was to explore whether SNPs of genes involved in cell cycle and NF-κB pathways are associated with responses to radiotherapy in NPC patients. We selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-κB pathway and genotyped them in 154 NPC patients treated with radiotherapy. Multivariate logistic regression was used to determine the association of these 8 SNPs with the responses to radiotherapy. We observed that cyclin-dependent kinase inhibitor gene CDKN2A rs3088440 was significantly related with a poorer treatment efficacy on the primary tumor and cervical lymph node after radiotherapy, and also with a decreased risk of grade 3–4 acute radiation-induced myelosuppression. In some subgroups, cyclin D1 gene CCND1 rs9344 and inhibitor of κB kinase gene IKBKB rs12676482 were related with the grade 3–4 acute radiation-induced myelosuppression, and CCND1 rs9344 was also associated with grade 3–4 acute radiation-induced oral mucositis. The current results reveal that SNPs in genes of cell cycle pathwayand NF-κB pathway have the potential to predict the clinical responses to radiotherapy for NPC patients.

Investigation of &lt;em&gt;cyclin D1&lt;/em&gt; rs9344 G&amp;gt;A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects

The relationship between cyclin D1 (CCND1) rs9344 G>A polymorphism and colorectal cancer (CRC) risk is still ambiguous. To obtain a precise estimation of the relationship, we performed an extensive meta-analysis based on the eligible studies. Crude odds ratios with their 95% confidence intervals were harnessed to determine the strength of correlation between CCND1 rs9344 G>A polymorphism and CRC risk under the allele, the homozygote, the dominant, and the recessive genetic models, respectively (28 studies with 5,784 CRC cases and 7,858 controls). Our results indicated evidence of the association between CCND1 rs9344 G>A polymorphism and the increased risk of CRC in four genetic models: A vs G, AA vs GG, AA+GA vs GG, and AA vs GA+GG. In a stratified analysis by cancer type of CRC, there was an increased risk of sporadic CRC found in three genetic models: A vs G, AA vs GG, and AA+GA vs GG. In a stratified analysis by ethnicity, there was an increased CRC risk found among Asians in allele comparison genetic models, as well as Caucasians in two genetic models: AA+GA vs GG and A vs T. In summary, this meta-analysis demonstrates that CCND1 rs9344 G>A polymorphism may be a risk factor for CRC.

Abstract 460: Diagnostic and prognostic value of expression of CCND1 splice variant cyclin D1b in papillary thyroid carcinoma

Abstract Background: An active cyclin D1 isoform, cyclin D1b, arises as a result of a failure to splice the fourth intron of the CCND1 pre-mRNA transcript. The expression of cyclin D1b has been associated with tumorigenesis and tumor progression in many types of human cancer. However, no studies with cyclin D1b have yet been reported in the thyroid cancer. Methods: We investigated the CCND1 rs9344 (cDNA 870) polymorphism by TaqMan SNP genotyping assay and expression profiles of mRNA and protein of full-length cyclin D1 (cyclin D1a) and cyclin D1b by quantative real-time PCR and immunohistochemistry in 286 thyroid tumors including 16 nodular hyperplasias, 33 follicular adenomas (FA), 179 papillary thyroid carcinomas (PTC), 32 follicular thyroid carcinomas (FTC), 5 poorly differentiated carcinomas (PDC), 4 anaplastic thyroid carcinomas (ATC), and 17 medullary thyroid carcinomas (MTC). The relationships between cyclin D1 expression levels and clinicopathological features were analyzed. Results: The cyclinD1b mRNA expression level in all thyroid tumors was significantly higher in the AA and GA genotype groups compared with the GG genotype group (p&amp;lt;0.001 and p = 0.006, respectively). The mRNA expression levels of cyclin D1b was significantly higher in PTCs when compared to benign or other malignant tumors (p&amp;lt;0.001) while no significant difference in cyclin D1a mRNA expression was observed according to the genotypes or tumor types. PTCs showed similar expression levels of cyclin D1b mRNA regardless of histologic subtypes, even when compared with follicular variant. In immunohistochemistry analysis, cyclin D1b overexpression was observed in PTC, PDC, ATC, and MTC, but not in FA and FTC. Cytoplasmic overexpression of cyclin D1b was significantly associated with advanced tumor stage in all PTCs (p = 0.025). Nuclear overexpression of cyclin D1b was associated with an increased incidence of lymph node metastases (p = 0.014) in classic PTCs. Conclusion: The A allele of the rs9344 polymorphism predisposes for cyclin D1b production in thyroid cancer. Cyclin D1b overexpression has a diagnostic biomarker utility to differentiate PTC from benign follicular nodules and may be functionally involved in the progression of the disease. Citation Format: Chan Kwon Jung, Sora Jeon, Yourha Kim, Ahwon Lee, Gyeong Sin Park. Diagnostic and prognostic value of expression of CCND1 splice variant cyclin D1b in papillary thyroid carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 460.

A common and functional gene variant in the vascular endothelial growth factor a predicts clinical outcome in early‐stage breast cancer

Angiogenesis and cell cycle control play critical roles in breast cancer susceptibility and clinical outcome and are mainly controlled by vascular endothelial growth factor (VEGF) and cyclin-dependent kinases, respectively. Functional germline polymorphisms in these genes alter the function, thereby causing inter-individual differences in breast cancer risk and clinical outcome. In this study, we investigated the influence of the functional polymorphisms VEGF-A rs3025039 C > T and CCND1 rs9344 G > A on risk and clinical outcome in early-stage breast cancer. DNA of 539 female patients with histologically confirmed early-stage breast cancer and 804 control subjects was genotyped for these polymorphisms. Genotypes were tested for associations with breast cancer risk and clinical outcome. There was no significant association between the polymorphisms and breast cancer risk. However, the minor allele of VEGF-A rs3025039 C > T was significantly associated with decreased recurrence-free survival (HR 1.845; 95% confidence interval [CI] 1.035-3.290; P = 0.038) and remained significant in multivariate analysis (HR 1.880; 95% CI 1.020-3.465; P = 0.043). Patients carrying at least one A-allele in CCND1 rs9344 G > A showed a trend towards decreased recurrence-free survival in univariate analysis (HR 2.379; 95% CI 0.841-6.728; P = 0.068). This study provides evidence that the functional VEGF-A rs3025039 C > T polymorphism influences recurrence-free survival in early-stage breast cancer.

The cyclin D1 (CCND1) rs9344 G&gt;A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy

Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G>A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G>A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G>A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G>A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings.

Prognostic Significance of Cyclin D1 Polymorphisms on Prostate-Specific Antigen Recurrence After Radical Prostatectomy

Cyclin D1 (CCND1) is an important cell-cycle regulator involved in carcinogenesis and progression of prostate cancer. We tested whether genetic variations within the CCND1 gene are related to clinical outcomes in prostate cancer patients receiving radical prostatectomy. A total of 320 clinical localized prostate cancer patients who underwent radical prostatectomy in Taiwan were prospectively follow-up in this study. A total of 5 tagged single-nucleotide polymorphisms that captured the genetic variability across the CCND1 gene were genotyped, and the prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using the Kaplan-Meier analysis and Cox regression model. We found a polymorphism, rs9344, and 2 haplotypes, GAGG and CTGG, consisting of rs667515, rs2450254, rs9344, and rs678653, were associated with PSA recurrence (P ≤ 0.033). After adjusting for other clinicopathologic predictors, including age, PSA levels, pathologic stage, Gleason score, and surgical margin, rs9344 and the haplotype CTGG remained significant (P ≤ 0.044). The model based on clinical variables plus CCND1 rs9344 or haplotype showed improvement over the model without genetic information, as indicated by ≥ 7.2 % net reclassification improvement (P ≤ 0.040), integrated discrimination index (P ≤ 0.041), and likelihood ratio test (P ≤ 0.028). Our data suggest that the CCND1 rs9344 and a specific haplotype CTGG may be prognostic factors for PSA recurrence after radical prostatectomy.

Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an Argentinian population

ObjectivesTo determine the frequencies of relevant allelic variants in oncology for the GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in a population from Central Argentina. To compare the allelic distribution found with the frequencies reported for other ethnic groups. Design and methodsGenotyping was carried out in a total of 102 unrelated Argentinian subjects. FCGR3A (rs396991) was detected using allele specific polymerase chain reaction (PCR) assay, while GSTP1 (rs1695), DPYD (rs3918290), FCGR2A (rs1801274) and CCND1 (rs9344) variants were assessed by PCR-restriction fragment length polymorphism (PCR-RFLP). ResultsThe allele frequencies for GSTP*1B, DPYD*2A, FCGR2A (131R), FCGR3A (158F) and CCND1 (870G) in Argentinians were 0.35, 0.005, 0.41, 0.77 and 0.47, respectively. ConclusionsWe found that the Argentinian population tested resembles other Caucasians populations, especially Spaniards; yet the differences in allele distribution with other Caucasian groups, uncover population admixture with native Amerindian and other ethnic groups, consistent with the well documented immigration flows landing Argentina from several countries.

CCND1 rs9344 polymorphisms are associated with the genetic susceptibility to cervical cancer in Chinese population

Cyclin D1, with a common G/A polymorphism in rs9344, is an essential regulator of the G1 phase in cell cycles and plays an important role in several tumor types, and the homology of cyclin D1 with human papillomavirus (HPV)-16 E7 brought our attention to CCND1 gene in cervical cancer. A total of 738 native Chinese subjects consist of 327 cases and 411 controls were enrolled in this study. CCND1 genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and partially verified by sequencing of genomic DNA and cDNA. The transcription of cyclin D1 mRNA isoforms was analyzed by quantitative PCR; expression of protein isoforms by immunohistochemistry and Western blotting. We observed that the AA genotype had decreased risk of developing cervical cancer (odds ratio [OR] = 0.332; 95% confidence interval [CI] = 0.113-0.978; P = 0.045). The two mRNA isoforms were both transcripted from A and G allele. Transcript b decreased in squamous cell carcinoma of the uterine cervix (SCCUC) group (P = 0.004), especially poorly differentiated group (P = 0.004), and in G allele group of normal subjects (P = 0.001). In immunohistochemistry analysis, cyclins D1, D1a, and D1b failed to correlate with cervical cancer (P = 0.808, 0.445, and 0.095). However, cyclin D1b was downregulated in SCCUC group analyzed by Western blotting (P = 0.039). This study indicates that CCND1 rs9344 polymorphisms confer host susceptibility to cervical cancer. A allele possesses a relative protective effect probably through the cyclin D1b's inhibition on HPV carcinogenesis.