ABSTRACT
We analyzed a possible association between RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer (CRC). Genomic DNA samples were obtained from the peripheral blood of 176 Mexican patients with CRC at diagnosis and from 195 individuals that formed the control group. The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Association was estimated by odds ratio (OR). The haplotypes and linkage disequilibrium were established using the Arlequin v3.5 software. We found that the RUNX3 polymorphisms analyzed were in Hardy-Weinberg equilibrium. The RUNX3 rs2236852 AA genotype and A allele showed association with CRC (OR = 0.39, 95%CI = 0.21-0.73, P < 0.01; OR = 0.65, 95%CI = 0.49-0.87, P < 0.01, respectively), while the rs6672420, rs11249206, and rs760805 polymorphisms did not show significant association with CRC. The TA haplotype (SNPs rs760805 and rs2236852) showed an increased risk for CRC (OR = 2.52, 95%CI = 1.47-4.30, P < 0.001). In conclusion, we found that the AA genotype and A allele of rs2236852 polymorphism confer a decreased CRC risk, while the TA haplotype appears to increase the risk of CRC development in Mexican patients.
Subject(s)
Colorectal Neoplasms/genetics , Core Binding Factor Alpha 3 Subunit/genetics , Genetic Predisposition to Disease , Haplotypes , Polymorphism, Single Nucleotide , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Female , Humans , Male , Mexico , Middle Aged , Odds Ratio , Risk Factors , Young AdultABSTRACT
The ZNF217 gene, a potential oncogene amplified and overexpressed in several cancers including colorectal cancer (CRC), acts as a transcription factor that activates or represses target genes. The polymorphisms rs16998248 (T>A) and rs35720349 (C>T) in coronary artery disease have been associated with reduced expression of ZNF217. In this study, we analyzed the 2 polymorphisms in Mexican patients with CRC. Genotyping of rs16998248 and rs35720349 sites was performed by polymerase chain reaction-restriction fragment length polymorphism in 203 Mexican Mestizos, 101 CRC patients, and 102 healthy blood donors. Although no statistical differences regarding genotype and allele frequencies of ZNF217 polymorphisms were observed (P > 0.05), linkage disequilibrium was significant in CRC patients (r(2) = 0.39, P < 0.0001), as a result of reduced AC haplotype frequency. Thus, the AC haplotype may protect against CRC.
Subject(s)
Carcinogenesis/genetics , Colorectal Neoplasms/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Trans-Activators/genetics , Case-Control Studies , Gene Frequency/genetics , Humans , MexicoABSTRACT
Colorectal cancer (CRC) is characterized by enhanced expression and activity of several metalloproteinases (MMPs), including MMP13 and MMP7, which play an important role in tumor invasion and metastasis. The objective of this study was to analyze the association of functional MMP7-181A/G and MMP13-77A/G promoter polymorphisms with susceptibility to CRC in a Mexican population. Genomic DNA samples were obtained from peripheral blood of 102 CRC patients and 125 blood donors who were included as the control group. Identification of polymorphisms was based on polymerase chain reaction-restriction fragment length polymorphism methodology. The association was estimated by the odds ratio (OR) test. The results showed that MMP7-181A/G and MMP13-77A/G variants were associated with CRC. For MMP7-181A/G, the AA (P=0.02, OR=3.38, 95% confidence interval (CI)=1.16-9.84) and AG (P=0.01, OR=3.4, 95%CI=1.17-9.83) genotypes were associated with an increased risk of CRC. For MMP13-77A/G, the AA and AG genotypes were associated with CRC (AA genotype: P=0.04, OR=3.2, 95%CI=1.004-10.2; AG genotype: P=0.01, OR=4.08, 95%CI=1.3-13.07). In conclusion, AA and AG genotype carriers for both polymorphisms are at a higher risk of developing CRC in this Mexican population.
Subject(s)
Colorectal Neoplasms/genetics , Matrix Metalloproteinase 14/genetics , Matrix Metalloproteinase 7/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Population , Promoter Regions, GeneticABSTRACT
Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease. Currently, severity Global initiative for chronic Obstructive Lung Disease (GOLD) criteria are used to diagnose the severity of COPD, but a new grading system, the body mass index, bronchial obstruction, dyspnea, exercise (BODE) index, was recently proposed to provide useful prognostic information. The objective of this study is to evaluate the association between health-related quality of life (HRQOL) and COPD severity assessed by two criteria: the GOLD classification and the BODE index. Sixty-four patients with COPD were examined with lung function tests and specific and generic HRQOL questionnaires (St. George's Respiratory Questionnaire [SGRQ], Nottingham Health Profile [NHP]). Participants were divided into four severity groups using the GOLD guidelines and the BODE index quartiles. The association between NHP and SGRQ subscales, and the BODE index was significant (P < 0.01). However, the GOLD classification shows a correlation only with SGRQ total score (P < 0.05) but not with NHP or SGRQ subscales. There was an association of the SGRQ total score between the severity groups of BODE (P = 0.0001), but there was no difference in the SGRQ total score between the severity groups of GOLD classification (P = 0.244). The present study suggests that COPD severity assessed by the BODE index can be more directly related with HRQOL.
