Antioxidant vitamins intake, ataxia telaniectasia mutated (ATM) genetic polymorphisms, and breast cancer risk
ABSTRACT Ataxia telangiectasia mutated (ATM) cells exist under a constant state of oxidative stress with high levels of reactive oxygen species, which are removed by cellular antioxidant vitamins. We investigated the independent and combined effect of antioxidant vitamins intake and the ATM genotype or diplotype on the breast cancer risk. Analyses included 323 cases and age-matched controls who participated in the Korean Breast Cancer Study during 2001-2003 with complete dietary information. The vitamin A (P < 0.01) and α-tocopherol (P < 0.01) were associated with lower breast cancer risk as well as some water-soluble vitamins including vitamin B(2) (P = 0.01), vitamin C (P < 0.01), and folic acid (P = 0.02) intake. No five single nucleotide polymorphisms (ATM-5144A > T (rs228589), IVS21 + 1049T > C (rs664677), IVS33-55T > C (rs664982), IVS34+60G > A (rs664143), and 3393T > G (rs4585)) studied showed significant differences in their allele frequencies between the cases and controls. On the other hand, compared with the diploid of ATTGT/ATTGT, as the number of ATTGT haplotype decreased, the risk of breast cancer increased (P = 0.04). The association between ATM diplotype and the breast cancer risk was predominantly among women with low intake of antioxidant vitamins including vitamin A, vitamin C, and folic acid. This study suggested that some antioxidant vitamins intake may modify the effect of ATM diplotype on the breast cancer risk among Korean women.
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ABSTRACT: Recent compelling evidence indicates that mutation, aberrant expression, and dysregulation of microRNA (miRNA) biogenesis are implicated in cancer development and progression. Based on the important role of miRNA biogenesis pathway in carcinogenesis, we hypothesized that genetic variations in this pathway genes may play a role as susceptibility factors for breast cancer. To test this hypothesis, we investigated the associations between 41 single nucleotide polymorphisms (SNPs) in 14 genes involved in miRNA biogenesis pathway and breast cancer risk in a case-control study of 559 Korean breast cancer cases and 567 controls frequency-matched by age. In all women, 3 SNPs (AGO1 rs595055, AGO2 rs3864659, and p68 rs1991401) were significantly associated with breast cancer risk. In stratified analysis by menopausal status, altered risk associations were observed for 7 SNPs in postmenopausal breast cancer. When subjects were grouped by the number of high-risk genotypes, we found a progressive increase in gene-dosage effect (P (trend) = 9.46E-7). The protective effects of AGO2 rs3864659 and HIWI rs11060845 were more pronounced in progesterone receptor-positive (PR+) cancer than in progesterone receptor-negative (PR-) cancer (odds ratio (OR), 0.50; 95% confidence interval (CI), 0.30-0.84 vs. OR, 0.94; 95% CI, 0.60-1.84; P (heterogeneity) = 0.04 and OR, 0.57; 95% CI, 0.37-0.88 vs. OR, 0.97; 95% CI, 0.65-1.44; P (heterogeneity) = 0.02, respectively), and the DROSHA rs644236 had stronger association with estrogen receptor-negative (ER-) cancer than for estrogen receptor-positive (ER+) cancer (OR, 1.39; 95% CI, 1.08-1.78 vs. OR, 1.05; 95% CI, 0.85-1.29; P (heterogeneity) = 0.04). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer risk, and the modifiable effects might be different according to the menopausal status and hormone receptor status.Breast Cancer Research and Treatment 07/2011; 130(3):939-51. DOI:10.1007/s10549-011-1656-2 · 4.20 Impact Factor
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ABSTRACT: BACKGROUND: Oxidative stress and trace elements have been implicated in the development of breast cancer. However, how they contribute to the pathogenesis of the disease and the relationship between them remain unclear. In addition, most previous studies detecting one or a few oxidant/antioxidant markers failed to consider the overall oxidant/antioxidant status of the subjects. This study was designed to address this and to investigate the association between oxidative status and trace elements in the pathogenesis of breast cancer. METHODS: Fifty-six patients with breast carcinoma at different clinical stages, 32 patients with benign breast tumor, and 20 healthy subjects (controls) were recruited into this study. Their serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and levels of Cu, Zn, Fe, Se, Mg, and Mn were measured. RESULTS: Levels of TAS, TOS, OSI, and trace elements significantly differed between the study groups. Among subgroups of patients with different clinical stages of breast cancer, the levels of all the trace elements except Zn were similar, whereas TAS, TOS, and OSI levels were all significantly different. There were significant correlations between oxidative stress parameters and levels of trace elements in patients with breast carcinoma but not in patients with benign breast tumor or in the healthy controls. CONCLUSIONS: Disturbed oxidative stress status and trace element levels may contribute to the pathogenesis of breast tumors. TAS, TOS, and OSI may be useful biomarkers for monitoring the clinical status of breast cancer.International Journal of Clinical Oncology 10/2011; DOI:10.1007/s10147-011-0327-y · 2.17 Impact Factor
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ABSTRACT: To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case-control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02-1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18-1.85, AA vs. GG: OR = 1.51, 95% CI 1.18-1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62-0.92, CC vs. TT: OR = 0.80, 95% CI 0.64-0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17-1.73, CC vs. TT: OR = 1.51, 95% CI 1.21-1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20-1.63, AA vs. GG: OR = 1.37, 95% CI 1.16-1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.Molecular Biology Reports 12/2011; 39(5):5719-25. DOI:10.1007/s11033-011-1381-2 · 1.96 Impact Factor