Antioxidant vitamins intake, ataxia telangiectasia 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: A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after childhood exposure to ionizing radiation from the Chernobyl nuclear accident has been described as the largest number of tumours of one type due to one cause that have ever occurred. Inter-individual variations in response to radiation have been documented and the role of genetics in sporadic PTC is well established, suggesting that genetic factors may also affect the risk of radiation-related PTC. To investigate how environmental and host factors interplay to modify PTC risk, we genotyped 83 cases and 324 matched controls sampled from children living in the area contaminated by fallout from the Chernobyl power plant accident for 19 polymorphisms previously associated with PTC, thyroid biology or radiation-induced second primary tumours. Significant association with PTC was found for rs1801516 (D1853N) in ATM (OR=0.34, 95%CI 0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR=1.55, 95%CI 1.03, 3.34). Analysis of additional polymorphisms confirmed the association between these two genes and PTC. Our findings suggest that both DNA double-strand break repair pathway and thyroid morphogenesis pathway or dysregulation of thyroid differentiated state maintenance are involved in the aetiology of PTC, and that the studied SNPs and radiation dose appear to act as independent multiplicative risk factors for PTC. © 2013 Wiley Periodicals, Inc.International Journal of Cancer 09/2013; · 6.20 Impact Factor
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ABSTRACT: There is conflicting epidemiological evidence on the role of folate and breast cancer risk. We conducted a systematic review and quantitative meta-analysis of folate intake and folate blood levels and the risk of breast cancer. Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched to April 11, 2014, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of breast cancer. The meta-analysis of dietary folate intake comprising 36 studies with 34,602 cases, and a total sample size of 608,265 showed a decreased risk of breast cancer, with an odds ratio (OR) of 0.84 [95 % confidence interval (CI) 0.77-0.91]. When stratified by menopausal status and by study design, none of the meta-analyses of prospective studies showed any statistically significant decrease in the risk of breast cancer. The meta-analysis of total folate showed no statistically significant association with breast cancer OR of 0.98 (95 % CI 0.91-1.07). There was no significant association between either dietary or total folate intake and breast cancer when stratified by hormonal receptor status. The meta-analysis of blood folate levels found no significant association with the risk of breast cancer, with an OR of 0.86 (95 % CI 0.60-1.25). Breast cancer does not appear to be associated with folate intake, and this did not vary by menopausal status or hormonal receptor status. Folate blood levels also do not appear to be associated with breast cancer risk.Breast Cancer Research and Treatment 04/2014; · 4.47 Impact Factor
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ABSTRACT: Background:Many epidemiological studies have investigated the association between folate intake, circulating folate level and risk of breast cancer; however, the findings were inconsistent between the studies.Methods:We searched the PubMed and MEDLINE databases updated to January, 2014 and performed the systematic review and meta-analysis of the published epidemiological studies to assess the associations between folate intake level, circulating folate level and the overall risk of breast cancer.Results:In all, 16 eligible prospective studies with a total of 744 068 participants and 26 205 breast cancer patients and 26 case-control studies with a total of 16 826 cases and 21 820 controls that have evaluated the association between folate intake and breast cancer risk were identified. Pooled analysis of the prospective studies and case-control studies suggested a potential nonlinearity relationship for dietary folate intake and breast cancer risk. Prospective studies indicated a U-shaped relationship for the dietary folate intake and breast cancer risk. Women with daily dietary folate intake between 153 and 400 μg showed a significant reduced breast cancer risk compared with those <153 μg, but not for those >400 μg. The case-control studies also suggested a significantly negative correlation between the dietary folate intake level and the breast cancer risk. Increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake. No significant association between circulating folate level and breast cancer risk was found when the results of 8 identified studies with 5924 participants were pooled.Conclusions:Our studies suggested that folate may have preventive effects against breast cancer risk, especially for those with higher alcohol consumption level; however, the dose and timing are critical and more studies are warranted to further elucidate the questions.British Journal of Cancer advance online publication, 25 March 2014; doi:10.1038/bjc.2014.155 www.bjcancer.com.British Journal of Cancer 03/2014; · 5.08 Impact Factor