Genetic variants of myeloperoxidase and catechol-O-methyltransferase and breast cancer risk

Sc, Lin; Yc, Chou; Mh, Wu; Wu, Can; Wy, Lin; Cp, Yu; Jc, Yu; Sl, You; Cj, Chen; Ca, Sun

doi:10.1097/00008469-200506000-00010

Cited by 25 publications

(20 citation statements)

References 10 publications

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“…We found a non-significant inverse association between MPO homozygous variant genotype and breast cancer risk, providing weak support for this biologically plausible hypothesis. This result was consistent with two previous studies, which both reported a decreased breast cancer risk associated with MPO AA genotype [17,18]. In the Long Island Breast Cancer Project, Ahn et al observed a non-significant 17% reduction in risk associated with being homozygous for the A allele [17].…”

Section: Discussionsupporting

confidence: 91%

“…In the Long Island Breast Cancer Project, Ahn et al observed a non-significant 17% reduction in risk associated with being homozygous for the A allele [17]. Lin et al found that women with the MPO AA genotype had an OR of 0.64 (95% CI, 0.11-3.76) in a Chinese population [18].…”

Section: Discussionmentioning

confidence: 99%

“…This polymorphism has been reported to be associated with cancer risk at several sites [11][12][13][14][15][16]. For breast cancer, two studies have reported a nonsignificant decrease in breast cancer risk associated with the AA genotype [17,18]. Another study found no significant association between the MPO G-463A polymorphism and postmenopausal breast cancer risk [19].…”

Section: Introductionmentioning

confidence: 99%

“…A non-synonymous polymorphism in COMT (Val158 Met, rs4680) leads to reduced enzyme activity [26], which is hypothesized to increase breast cancer risk through reduction in protecting DNA damage from ROS and accumulation of estradiol catechol metabolites. Lin et al reported an interaction between the MPO G-463A and COMT Val158Met polymorphisms on breast cancer risk, with an elevated risk associated with the increasing numbers of high-risk genotypes in both genes among women with longer duration between menarche and first full-term pregnancy [18].…”

Section: Introductionmentioning

confidence: 99%

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A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

Tamimi

Hankinson

et al. 2008

Breast Cancer Res Treat

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Oxidative stress may be involved in breast carcinogenesis. Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species (ROS). A single nucleotide polymorphism (SNP) G-463A in the promoter region has been associated with a decrease in risk of breast cancer. We assessed the association between this polymorphism and breast cancer risk in a nested case-control study within the Nurses' Health Study (1,269 incident breast cancer cases and 1,761 matched controls). We further investigated potential gene-gene and gene-environment interactions. There were no significant associations between MPO or COMT genotypes and risk of breast cancer. However, the combination of a priori hypothesized low-risk genotypes in MPO and COMT genes was associated with a marginally significant decrease in breast cancer risk (OR, 0.28; 95% CI, 0.08-1.00). Dietary intake and plasma antioxidant levels may modify the association between the MPO polymorphism and breast cancer risk. Although the test for departure from multiplicative interaction was not significant, inverse associations with MPO genotype were more pronounced among women who consumed higher amounts of total fruits and vegetables (OR, 0.58; 95% CI, 0.30-1.12); this association was not found among the low-consumption group (OR, 1.11; 95% CI, 0.63-1.96). The relative risk associated with the MPO homozygous variant genotype was 0.44 (95% CI, 0.18-1.09) for women who had the highest level of plasma carotenoids. Results from this study suggest that exogenous and endogenous modulators of oxidative stress may modify the association between the MPO polymorphism and breast cancer risk. Further research is needed to confirm these possible associations.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

Tamimi

Hankinson

et al. 2008

Breast Cancer Res Treat

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“…However, these negative results do not entirely exclude the potential role of polymorphisms of these genes in the aetiology of breast cancer, even though similar results were reported by previous studies. 22,23 In addition, although the results from our study indicated that SNPs of MnSOD1183T.C and GPx1Pro198Leu showed significant association with the risk of breast cancer, O 2…”

Section: á2mentioning

confidence: 57%

Oxidative stress-related enzyme gene polymorphisms and susceptibility to breast cancer in non-smoking, non-alcohol-consuming Taiwanese women: a case-control study

Tsai

Hou

et al. 2012

Ann Clin Biochem

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Background: Mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide anion into H 2 O 2 , which is neutralized sequentially by either catalase (CAT) or glutathione peroxidase 1 (Gpx 1) into water or converted into highly reactive hypochlorous acid by myeloperoxidase (MPO). We hypothesize that gene variants for these enzymes might be associated with the risk of breast cancer in non-smoking, non-alcohol-consuming women. Methods: Genotypes of oxidative stress-related enzymes (MnSOD1183T.C, MPO-463G.A, GPx1Pro198Leu and CAT-262C.T) were analysed in 260 non-smoking and non-alcohol-consuming female patients with breast cancer and 224 habitmatched controls. Results: Subjects with the MnSOD1183T.C C carrier or those with the GPx1Pro198Leu CT genotype had significantly decreased age-adjusted risks (odds ratio [OR]: 0.56 and 0.16 with 95% confidence intervals [95% CI]: 0.38-0.83 and 0.08-0.29, respectively) for breast cancer. Certain combined genotypes of the polymorphisms also significantly modulated the age-adjusted risk. Conclusions: We conclude that oxidative stress-related enzyme genetic variants, especially GPx1Pro198Leu CT, modify the risk of breast cancer development in non-smoking and non-alcohol-consuming women. The role of unidentified environmental factors predisposing to breast cancer development through an oxidative stress mechanism merits further investigation.

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Lack of association between catechol-O-methyltransferase Val108/158Met polymorphism and breast cancer risk: a meta-analysis of 25,627 cases and 34,222 controls

Chen

Wang

Qiu

et al. 2009

Breast Cancer Res Treat

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Epidemiological studies have evaluated the association between catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 41 studies including 25,627 cases and 34,222 controls were identified. Genotype distributions of COMT in the controls of all studies were in agreement with the Hardy-Weinberg equilibrium (HWE) except for three studies. When all 41 studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val108/158Met polymorphism and breast cancer risk (for Val/Met vs. Val/Val: OR = 0.99, 95% CI = 0.93-1.04; for Met/Met vs. Val/Val: OR = 0.96, 95% CI = 0.88-1.04; for dominant model: OR = 0.97, 95% CI = 0.92-1.03; for recessive model: OR = 0.97, 95% CI = 0.90-1.04). In the subgroup analyses by ethnicity, menopausal status, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that COMT Val108/158Met polymorphism is not associated with increased breast cancer risk.

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Genetic variants of myeloperoxidase and catechol-O-methyltransferase and breast cancer risk

Cited by 25 publications

References 10 publications

A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

Oxidative stress-related enzyme gene polymorphisms and susceptibility to breast cancer in non-smoking, non-alcohol-consuming Taiwanese women: a case-control study

Lack of association between catechol-O-methyltransferase Val108/158Met polymorphism and breast cancer risk: a meta-analysis of 25,627 cases and 34,222 controls

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