The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women.

PURPOSE: Xenobiotic metabolism is related to the interplay between diet and breast cancer (BC) risk. This involves detoxification enzymes, which are polymorphic and metabolise various dietary metabolites. An important characteristic of this pathway is that chemoprotective micronutrients can act not only as substrates but also as inducers for these enzymes. We investigated whether functional GSTP1 (p.Ile105Val-rs1695), NAT2 (590G>A-rs1799930) SNPs and GSTM1 and GSTT1 deletion polymorphisms could modulate the effect of the Mediterranean diet (MD) on BC risk, in Greek-Cypriot women. METHODS: Genotyping was performed on women from the MASTOS case-control study of BC in Cyprus. A 32-item food-frequency questionnaire was used to obtain dietary intake information. A dietary pattern, which closely resembles the MD (high loadings of vegetables, fruit, legumes and fish), was previously derived with principal component analysis and was used as our dietary variable. RESULTS: GSTT1 null genotype increased BC risk compared with the homozygous non-null GSTT1 genotype (OR 1.21, 95 % CI 1.01-1.45). Increasing adherence to the MD reduced BC risk in women with at least one GSTP1 Ile allele (OR for Ile/Ile = 0.84, 95 % CI 0.74-0.95, for Ile/Val = 0.73, 95 % CI 0.62-0.85) or one NAT2 590G allele (OR for 590 GG = 0.73, 95 % CI 0.63-0.83, for 590 GA = 0.81, 95 % CI 0.70-0.94). p interaction values were not, however, statistically significant. CONCLUSION: The homozygous null GSTT1 genotype could be a risk allele for BC among Greek-Cypriot women. The anticarcinogenic effects of the high adherence to MD against BC risk could also be further enhanced when combined with the wild-type alleles of the detoxification GSTP1 or NAT2 SNPs.

Mediterranean diet-gene interactions: A targeted metabolomics study in Greek-Cypriot women.

SCOPE: A high adherence to the Mediterranean diet (MD) was previously associated with a decreased risk of breast cancer (BC) among Greek-Cypriot women. Additionally, particular polymorphisms were shown to modulate this MD-BC association. Herein, we aimed to investigate the effect of polymorphisms-MD interactions on the levels of specific metabolites that could be related to dietary adherence or enzymatic activity, which is itself modulated by polymorphisms. METHODS AND RESULTS: Greek-Cypriot women who were BC controls and had the lowest or the highest MD adherence (vegetables, fruit, legumes, fish) as assessed by principal component analysis (n = 564) were included. Participants were previously genotyped for nine polymorphisms of the one-carbon metabolism, oxidative stress, and xenobiotic metabolism. The serum levels of 14 metabolites that are key players in the aforementioned pathways were measured by UPLC-MS/MS. ANCOVA was used to assess polymorphism-MD interactions on metabolites' levels within a multivariate linear regression model. Statistically significant interactions between GSTM1 (where GST is glutathione S-transferase) deletion polymorphism and MD on flavin mononucleotide and on 5-methyltetrahydrofolate (5-MTHF) concentrations were observed. The MTHFR rs1801133 interacted significantly with MD on 5-MTHF concentration. CONCLUSION: Serum levels of flavin mononucleotide and 5-MTHF were shown to be influenced by interactions between GSTM1 deletion or MTHFR (rs1801133) polymorphisms and a dietary pattern, characteristic of MD.

MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women.

PURPOSE: Oxidative stress arises due to a cellular imbalance in oxidants and antioxidants and/or due to an altered activity of antioxidant enzymes, caused by SNPs. Oxidative stress increases susceptibility to breast cancer (BC) risk, and we previously showed that the Mediterranean diet (MD), which is rich in antioxidants, reduces BC risk in Greek-Cypriot women. Here, we investigated the effect of MnSOD (p.Val16Ala, rs4880) and CAT (-262C>T, rs1001179) SNPs on the association between the MD and BC risk in the case-control study of BC MASTOS in Cyprus. METHODS: Dietary intake data were obtained using a 32-item food frequency questionnaire, from which a dietary pattern was previously derived, using principal component analysis. This pattern included high loadings of vegetables, fruit, legumes and fish, a combination that closely resembles the MD and was used as our dietary variable. RESULTS: High vegetable intake lowered BC risk in women with at least one MnSOD Val allele (ORHigh vs. Low for Val/Val = 0.56, 95 % CI 0.35-0.88, for Val/Ala = 0.57, 95 % CI 0.39-0.82), or one CAT -262C allele (ORHigh vs. Low for -262CC = 0.66, 95 % CI 0.47-0.92, for -262CT = 0.53, 95 % CI 0.35-0.81). High fish intake conferred a decreased BC risk of CAT -262CC women (ORQ4 vs. Q1 0.66, 95 % CI 0.47-0.92) compared with the CAT -262TT women and low fish intake (ORQ2 vs. Q1 2.79, 95 % CI 1.08-7.17). Additionally, high fish intake reduced BC risk in MnSOD Val/Val women (ORQ4 vs. Q1 0.63, 95 % CI 0.40-0.98). p interaction values were, however, not statistically significant. CONCLUSION: Our results demonstrate that the antioxidative effects of the MD against BC risk may be enhanced by the wild-type alleles of the MnSOD or CAT SNPs among Greek-Cypriot women.

Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean diet and breast cancer risk: a case-control study in the Greek-Cypriot female population.

Single-nucleotide polymorphisms (SNPs) within genes of the one-carbon metabolism pathway have been shown to interact with dietary folate intake to modify breast cancer (BC) risk. Our group has previously demonstrated that the Mediterranean dietary pattern, rich in beneficial one-carbon metabolism micronutrients, protects against BC in Greek-Cypriot women. We aimed to investigate whether SNPs in the MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) genes modify the effect of the Mediterranean dietary pattern on BC risk. Dietary intake data were obtained using a 32-item food-frequency questionnaire. A dietary pattern specific to the Greek-Cypriot population, which closely resembles the Mediterranean diet, was derived using principal component analysis (PCA) and used as our dietary variable. Genotyping was performed on subjects from the MASTOS study, a case-control study of BC in Cyprus, using TaqMan assays. Adjusted odds ratios (ORs) were estimated using logistic regression analyses. High adherence to the PCA-derived Mediterranean dietary pattern further reduced BC risk with increasing number of variant MTHFR 677T alleles (ORQ4vs.Q1 for 677TT = 0.37, 95 % CI 0.20-0.69, for 677 CT = 0.60, 95 % CI 0.42-0.86). Additionally, high adherence to the Mediterranean dietary pattern decreased BC risk in subjects with at least one MTR 2756A allele (ORQ4vs.Q1 for 2756AA = 0.59, 95 % CI 0.43-0.81, for 2756AG = 0.59, 95 % CI 0.39-0.91) and in subjects with the MTHFR 1298CC genotype (ORQ4vs.Q1 0.44, 95 % CI 0.30-0.65). Overall P-interaction values, however, were not statistically significant. Our study suggests that these MTHFR and MTR SNPs may act as effect modifiers, highlighting their biological significance in the association between Mediterranean diet, the one-carbon metabolism pathway and BC.

The mediterranean dietary pattern and breast cancer risk in Greek-Cypriot women: a case-control study.

BACKGROUND: Diet has long been suspected to impact on breast cancer risk. In this study we evaluated whether the degree of adherence to a Mediterranean diet pattern modifies breast cancer risk amongst Greek-Cypriot women. METHODS: Subjects included 935 cases and 817 controls, all participating in the MASTOS case-control study in Cyprus. The study was approved by the Cyprus National Bioethics Committee. Information on dietary intakes was collected using an interviewer administered 32-item Food Frequency Questionnaire. Information on demographic, anthropometric, lifestyle, and other confounding factors was also collected. Adherence to the Mediterranean Diet pattern was assessed using two a-priory defined diet scores. In addition, dietary patterns specific to our population were derived using Principal Component Analysis (PCA). Logistic regression models were used to assess the association between the dietary patters and breast cancer risk. RESULTS: There was no association with breast cancer risk for either score, however, higher consumptions of vegetables, fish and olive oil, were independently associated with decreased risk. In addition, the PCA derived component which included vegetables, fruit, fish and legumes was shown to significantly reduce risk of breast cancer (ORs across quartiles of increasing levels of consumption: 0.89 95%CI: 0.65-1.22, 0.64 95%CI: 0.47-0.88, 0.67 95%CI: 0.49-0.92, P trend < 0.0001), even after adjustment for relevant confounders. CONCLUSIONS: Our results suggest that adherence to a diet pattern rich in vegetables, fish, legumes and olive oil may favorably influence the risk of breast cancer. This study is the first investigation of dietary effects on breast cancer risk in Cyprus, a country whose population has traditionally adhered to the Mediterranean diet.