The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women
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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.
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.
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.
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.
KeywordsMediterranean diet GSTP1 GSTM1 GSTT1 NAT2 Breast cancer
This work was supported by “Cyprus Research Promotion Foundation” grants 0104/13, 0104/17 and the Cyprus Institute of Neurology and Genetics. Maria G. Kakkoura is funded by the Eurobank Cyprus Scholarship provided through the Cyprus School of Molecular Medicine. Further, we would like to thank all the study participants and acknowledge the help of the following cancer patient’s organisations: the Pancyprian Association of Cancer Patients and Friends, Europa Donna Cyprus, the Cyprus Anticancer Society as well as Dr Vaios Partasides, director of the National breast cancer screening programme and his team. We also would like to express our appreciation to Doctors Eleni Kakouri, Panayiotis Papadopoulos, Yiola Marcou and Simon Malas as well as to all the nurses and volunteers who provided valuable help towards the recruitment of the study participants.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
The study was approved by the Cyprus National Bioethics Committee. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
- 6.Vera-Ramirez L, Ramirez-Tortosa MC, Sanchez-Rovira P, Ramirez-Tortosa CL, Granados-Principal S, Lorente JA, Quiles JL (2013) Impact of diet on breast cancer risk: a review of experimental and observational studies. Crit Rev Food Sci Nutr 53(1):49–75. doi: 10.1080/10408398.2010.521600 CrossRefGoogle Scholar
- 7.Gago-Dominguez M, Castelao JE, Sun CL, Van Den Berg D, Koh WP, Lee HP, Yu MC (2004) Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore. Carcinogenesis 25(11):2143–2147. doi: 10.1093/carcin/bgh230 CrossRefGoogle Scholar
- 8.Demetriou CA, Hadjisavvas A, Loizidou MA, Loucaides G, Neophytou I, Sieri S, Kakouri E, Middleton N, Vineis P, Kyriacou K (2012) The mediterranean dietary pattern and breast cancer risk in Greek-Cypriot women: a case-control study. BMC Cancer 12:113. doi: 10.1186/1471-2407-12-113 CrossRefGoogle Scholar
- 9.Reszka E, Wasowicz W, Gromadzinska J (2006) Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility. Br J Nutr 96(4):609–619Google Scholar
- 15.Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J (1997) Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem 272(15):10004–10012CrossRefGoogle Scholar
- 18.Egeberg R, Olsen A, Autrup H, Christensen J, Stripp C, Tetens I, Overvad K, Tjonneland A (2008) Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer in Danish postmenopausal women. Eur J Cancer Prev 17(1):39–47. doi: 10.1097/CEJ.0b013e32809b4cdd CrossRefGoogle Scholar
- 21.Kakkoura MG, Demetriou CA, Loizidou MA, Loucaides G, Neophytou I, Marcou Y, Hadjisavvas A, Kyriacou K (2015) Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean diet and breast cancer risk: a case-control study in the Greek-Cypriot female population. Genes Nutr 10(2):453. doi: 10.1007/s12263-015-0453-7 CrossRefGoogle Scholar
- 24.Loizidou MA, Cariolou MA, Neuhausen SL, Newbold RF, Bashiardes E, Marcou Y, Michael T, Daniel M, Kakouri E, Papadopoulos P, Malas S, Hadjisavvas A, Kyriacou K (2010) Genetic variation in genes interacting with BRCA1/2 and risk of breast cancer in the Cypriot population. Breast Cancer Res Treat 121(1):147–156. doi: 10.1007/s10549-009-0518-7 CrossRefGoogle Scholar
- 25.Ambrosone CB, Sweeney C, Coles BF, Thompson PA, McClure GY, Korourian S, Fares MY, Stone A, Kadlubar FF, Hutchins LF (2001) Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. Cancer Res 61(19):7130–7135Google Scholar
- 29.Karen-Ng LP, Marhazlinda J, Rahman ZA, Yang YH, Jalil N, Cheong SC, Zain RB (2011) Combined effects of isothiocyanate intake, glutathione S-transferase polymorphisms and risk habits for age of oral squamous cell carcinoma development. Asian Pac J Cancer Prev 12(5):1161–1166Google Scholar
- 31.Vogl FD, Taioli E, Maugard C, Zheng W, Pinto LF, Ambrosone C, Parl FF, Nedelcheva-Kristensen V, Rebbeck TR, Brennan P, Boffetta P (2004) Glutathione S-transferases M1, T1, and P1 and breast cancer: a pooled analysis. Cancer Epidemiol Biomark Prev 13(9):1473–1479Google Scholar
- 35.Lee SA, Fowke JH, Lu W, Ye C, Zheng Y, Cai Q, Gu K, Gao YT, Shu XO, Zheng W (2008) Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr 87(3):753–760Google Scholar
- 36.Fowke JH, Chung FL, Jin F, Qi D, Cai Q, Conaway C, Cheng JR, Shu XO, Gao YT, Zheng W (2003) Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res 63(14):3980–3986Google Scholar
- 46.Spitz MR, Duphorne CM, Detry MA, Pillow PC, Amos CI, Lei L, de Andrade M, Gu X, Hong WK, Wu X (2000) Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol Biomark Prev 9(10):1017–1020Google Scholar
- 47.Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79(6):935–945Google Scholar
- 48.Loizidou MA, Michael T, Neuhausen SL, Newbold RF, Marcou Y, Kakouri E, Daniel M, Papadopoulos P, Malas S, Hadjisavvas A, Kyriacou K (2009) DNA-repair genetic polymorphisms and risk of breast cancer in Cyprus. Breast Cancer Res Treat 115(3):623–627. doi: 10.1007/s10549-008-0084-4 CrossRefGoogle Scholar
- 51.FNDDS U (2011–2012) USDA food and nutrient database for dietary studies: what’s in the foods you eat search tool 2011–2012 [https://reedir.arsnet.usda.gov/codesearchwebapp/%28h1zdt555qfcnfm55pjp44h45%29/codesearch.aspx]