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Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

ABSTRACT: Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 (SOD1, OMIM: 147450) and catalase (CAT, OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG (SOD1) and CC (CAT) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008).

SUBMITTER: Jamhiri I

PROVIDER: S-EPMC5534523 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

Jamhiri Iman I Saadat Iraj I Omidvari Shahpour S

Molecular biology research communications 20170601 2

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In prese ...[more]

PMID: 28775994

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Project description:PurposeThe antioxidant enzymes pathway is considered the most important pathway involved in the repair of reactive oxygen species (ROS)-induced damage. Therefore, we investigate the possible association between polymorphisms of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPX) genes and age -related cataract development.MethodsThe study included 415 cataract patients (121 patients with cortical, 109 with nuclear, 59 with posterior subcapsular, and 126 with mixed type) and 386 healthy control group of similar age. Genotyping of SOD1-251A/G, CAT-21A/T, and GPX1-198C/T was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Differences in the frequencies were estimated using the χ(2) test and risk was estimated with an unconditional logistic regression after adjusting for age and gender.ResultsSOD1 G/G genotype frequency was significantly higher in cataract patients (p=0.012, OR=1.642, 95% CI=1.129-2.389). SOD1 A/A genotypes (p=0.001, OR=0.613, 95% CI=0.461-0.817) seem to have a protective role against cataract, and the G allele (p=0.001, OR=1.479, 95% CI=1.208-1.810) plays a dangeous effect against in the development of cataract. In CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls (p=0.226, OR=1.358, 95% CI=0.839-2.199; p=0.521, OR=1.205, 95% CI=0.726-2.001, respectively). Stratification by the subtypes revealed that association between SOD polymorphism and cataract was in cortical and mixed type cataract. The genotype frequency of the GG and AA of SOD1-251A/G was significantly different in cortical and mixed type cataract group (p=0.031; OR: 1.805, 95% CI: 1.076-3.026; p=0.002; OR: 2.229, 95% CI: 1.364-3.645; p=0.026; OR: 0.608, 95% CI: 0.396-0.933; p=0.001; OR: 0.474, 95% CI: 0.305-0.734, respectively) compared to healthy controls.ConclusionsResults suggest that the G/G genotype of the SOD1-251A/G polymorphism may be associated with an increased risk of cataract. However, in CAT-21A/T and GPX1-198C/T polymorphisms, there were no significant differences in the variant homozygous frequencies in patients compared to controls.

Project description:Selenium may affect prostate cancer risk via its plasma carrier selenoprotein P which shows dramatically reduced expression in prostate cancer tumors and cell lines. The selenoprotein P (SEPP1) Ala234 single nucleotide polymorphism (SNP) allele is associated with lower plasma selenoprotein P in men, reducing the concentration/activity of other antioxidant selenoproteins. Selenium status also modifies the effect of the mitochondrial superoxide dismutase (SOD2) SNP Ala16Val on prostate cancer risk. We investigated the relationship of these SNPs with prostate cancer risk. DNA from 2,975 cases and 1,896 age-matched controls from the population-based Prostate Cancer in Sweden study were genotyped using TaqMan assays. Cases were designated aggressive or nonaggressive prostate cancers at diagnosis by clinical criteria. Association with prostate cancer was investigated by logistic regression; gene-gene interaction using a general linear model. The mean plasma selenium concentration measured in 169 controls was relatively low (76.0 +/- 17.2 microg/L). SNP genotype distributions were in Hardy-Weinberg equilibrium. SOD2-Ala16+ men were at a greater risk of prostate cancer [odds ratios (OR), 1.19; 95% confidence intervals (CI), 1.03-1.37] compared with SOD2-Val16 homozygotes. Men homozygous for SEPP1-Ala234 who were also SOD2-Ala16+ had a higher risk of prostate cancer (OR, 1.43; 95% CI, 1.17-1.76) and aggressive prostate cancer (OR, 1.60; 95% CI, 1.22-2.09) than those who were SOD2-Val16 homozygotes (interaction, prostate cancer P = 0.05; aggressive prostate cancer P = 0.01). This interaction was stronger in ever-smokers: SOD2-Ala16+ men homozygous for SEPP1-Ala234 had an almost doubled risk of prostate cancer (OR, 1.97; 95% CI, 1.33-2.91; interaction P = 0.001). In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration.

Dataset Information

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

Publications

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

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