Abstract
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.
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Acknowledgments
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.
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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.
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Kakkoura, M.G., Loizidou, M.A., Demetriou, C.A. et al. The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women. Eur J Nutr 56, 545–555 (2017). https://doi.org/10.1007/s00394-015-1099-3
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DOI: https://doi.org/10.1007/s00394-015-1099-3