Interaction of CCND2, CDKN1A, and POLD3 Variants in Mexican Patients with Colorectal Cancer.

BACKGROUND: Colorectal cancer is the second cause of death by cancer around the world. Sporadic colorectal cancer is the most frequent (75%), and it is produced by the interaction of environmental, epigenetic, and genetic factors. The accumulation of single-nucleotide variants in genes associated with cell proliferation, DNA repair, and/or apoptosis could confer a risk to cancer. The aim of this study was to analyze the gene-gene interactions among CCND2 (rs3217901), CDKN1A (rs1059234 and rs1801270), and POLD3 (rs3824999) variants in Mexican patients with colorectal cancer. METHODS: We collected peripheral blood samples from 185 patients with sporadic colorectal cancer before treatment and from 185 unrelated blood donors as the reference group; all participants signed an informed consent form. DNA extraction was performed by Miller and Cetyltrimethylammonium bromide (CTAB)/ Dodecyltrimethylammonium bromide (DTAB) methods. Polymerase chain reaction- restriction fragment length polymorphism followed by polyacrylamide gel electrophoresis stained with AgNO3 methods were used to identify the variants rs3217901, rs1059234, rs1801270, and rs3824999. Odds ratio and single-nucleotide variant interaction were determined by single-locus analysis and Multifactorial Dimensionality Reduction software, respectively. RESULTS: No association was found for CCND2 and CDKN1A variants; yet, a significant association for the GG genotype, G allele, and recessive and additive models for the POLD3 variant was observed (P < .05). The single-nucleotide variant-single-nucleotide variant interaction revealed the combination rs1059234, rs3217901, and rs3824999 as the best model and the comparison showed an increased risk (P < .05). CONCLUSION: Single-locus and gene-gene interaction analyses disclosed that both the rs3824999 (POLD3) variant and the combination of rs3217901 (CCND2), rs1059234 (CDKN1A), and rs3824999 (POLD3) genotypes increase the risk for colorectal cancer in Mexican population.

Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the corticotropin-releasing hormone (CRH) family in CRC induction, including the low expression of corticotropin-releasing hormone receptor 2 (CRHR2), which is an angiogenesis inhibitor and inflammatory modulator. Previous research suggests that CRHR2 expression in colonic intestinal cells can regulate migration, proliferation and apoptosis through the modulation of several pathways. The aim of this study was to analyze the association of the rs10250835, rs2267716 and rs2267717 variants of CRHR2 gene with CRC in the Mexican population in order to consider its predictive value in CRC. This cross-sectional study included a group of 187 unrelated patients with sporadic CRC and a control group of 191 healthy blood donors. DNA extraction from peripheral blood was carried out using the Miller method. Identification of the rs10250835 variant was performed using PCR-restriction fragment length polymorphism (RFLP) and the rs2267716 and rs2267717 variants using TaqMan allelic discrimination assay. The minor allele homozygous CC of the rs2267716 variant of CRHR2 showed significant difference between CRC and control group (p=0.025), as well as the GCA haplotype (p=0.007), corresponding to the rs10250835, rs2267716 and rs2267717 variants, respectively. Our results suggest that the rs2267716 variant and GCA haplotype of CRHR2 represent a risk factor for CRC development in Mexican patients.

Methylation analysis of MIR200 family in Mexican patients with colorectal cancer.

The present study aimed to analyze the methylation pattern of the MIR200 family in the colorectal tissues and peripheral blood of colorectal cancer (CRC) patients. Previous informed consent, 102 samples of colorectal tissues (tumor and adjacent normal tissues) and 40 peripheral blood samples were collected from CRC patients. Additionally, we included a reference group of 40 blood samples. DNA extraction was done for colorectal tissues and peripheral blood. For methylation-specific PCR, we used bisulfite-treated DNA and controls for methylated and unmethylated DNA were included to each assay. PCR fragments were separated by 6% polyacrylamide gel electrophoresis. Methylation-positive and methylation-negative results were confirmed by bisulfite genomic sequencing technique. We analyzed 102 colorectal tissues and 40 blood samples from 51 CRC patients. MIR200B/MIR200A/MIR429 methylation analysis discloses no differences among tissues (p>0.05). However, MIR200C/MIR141 methylation showed differences between colorectal tissues and peripheral blood of CRC patients (p<0.0001) and mainly methylated alleles were observed in peripheral blood. These findings suggest a tissue-specific methylation pattern for the MIR200C/MIR141 promoter.

ADIPOQ rs2241766 SNP as protective marker against DIBC development in Mexican population.

BACKGROUND: Adiponectin protein and some variations in its gene, ADIPOQ have recently been associated with cancer because they regulate glucose and lipid metabolism as well as anti-apoptotic and anti-inflammatory proteins. AIM: The aim of this study was to analyse the relationship between selected biochemical markers, anthropometric indices and ADIPOQ rs2241766 and rs1501299 SNPs in ductal infiltrating breast cancer (DIBC) in a Mexican population. METHODS: This cross-sectional study included 64 DIBC patients and 167 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to identify the genotypes of the rs2241766 (exon 2) and rs1501299 (intron 2) ADIPOQ polymorphisms. Corporal composition and biochemical markers included body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), glucose, cholesterol, triglycerides and high- and low-density lipoprotein cholesterol. RESULTS: Patients with DIBC had higher serum glucose, WC and WHR than controls. Intergroup differences in allele and genotype frequencies were found for both polymorphisms (P < 0.05). Patients carrying the rs2241766 TT and TG genotypes had higher values of WC, HC and WHR, but only TG carriers had higher levels of glucose. For the SNP rs1501299, carriers of the GG genotype in the DIBC group had higher values of glucose, WC, HC and WHR than the respective control group. CONCLUSIONS: These results suggest that WC, HC and WHR are better predictors of DIBC than BMI. The ADIPOQ SNP rs2241766 emerges as a protective factor, whereas rs1501299 is a risk factor for DIBC development in a Mexican population.

46,XX ovotesticular disorder in a Mexican patient with Beckwith-Wiedemann syndrome: a case report.

INTRODUCTION: Beckwith-Wiedemann syndrome is an overgrowth syndrome that is characterized by hypoglycemia at birth, coarse face, hemihypertrophy and an increased risk to develop embryonal tumors. In approximately 15% of patients, the inheritance is autosomal dominant with variable expressivity and incomplete penetrance, whereas the remainder of Beckwith-Wiedemann syndrome cases are sporadic. Beckwith-Wiedemann syndrome molecular etiologies are complex and involve the two imprinting centers 1 (IC1) and 2 (IC2) of 11p15 region. This case report describes, for the first time, the unusual association of ovotesticular disorder in a patient from Morelia, Mexico with Wiedemann-Beckwith syndrome. CASE PRESENTATION: We report the case of a Mexican six-year-old girl with Beckwith-Wiedemann Syndrome, ambiguous genitalia, and bilateral ovotestes. She has a 46,XX karyotype without evidence of Y-chromosome sequences detected by fluorescence in situ hybridization with both SRY and wcp-Y probes. CONCLUSION: Although a random association between these two conditions cannot be excluded, future analysis of this patient with Beckwith-Wiedemann syndrome and 46,XX ovotesticular disorder may lead to new insights into these complex pathologies. We speculate that a possible misregulation in the imprinted genes network has a fundamental role in the coexistence of these two disorders.

Diastrophic dysplasia and atelosteogenesis type II as expression of compound heterozygosis: first report of a Mexican patient and genotype-phenotype correlation.

The osteochondrodysplasias represent a heterogeneous group of cartilage and bone diseases. Among these, achondrogenesis 1B, atelosteogenesis type II, diastrophic dysplasia, and autosomal recessive multiple epiphyseal dysplasia are caused by mutations in the solute carrier family 26 (sulfate transporter), member 2 gene (SLC26A2). This group of osteochondrodysplasias shows a continuous spectrum of clinical variability and shares many features in common. Usually, it is difficult to distinguish clinically among these patients. To date, several efforts have been made to correlate mutations in the SLC26A2 gene with phenotypic severity in the patients. We report on a Mexican girl with diastrophic dysplasia presenting some unusual clinical and radiographic features that are usually observed in atelosteogenesis type II. Molecular analysis of the SLC26A2 gene in this patient showed compound heterozygosity for the R178X and R279W mutations. In this patient, the combination of a mild and a severe mutation has apparently led to an intermediate or transitional clinical picture, showing an apparent genotype-phenotype correlation.