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Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent

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Abstract

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case–control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5′-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.

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Acknowledgment

This study is a support from CNPq, Rede Nordeste de Biotecnologia (RENORBIO).

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Authors and Affiliations

  1. Molecular Genetics Laboratory, Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo, 1315, Rodolfo Teófilo, Fortaleza, CE, CEP 60430-270, Brazil

    Rita de Cássia Carvalho Barbosa, Débora Costa Menezes, Thiago Fernando Vasconcelos Freire, Diogo Campos Sales & Silvia Helena Barem Rabenhorst

  2. Departamento de Fisiologia e Farmacologia, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil

    Victor Hugo Medeiros Alencar

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  1. Rita de Cássia Carvalho Barbosa
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Correspondence to Rita de Cássia Carvalho Barbosa.

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Carvalho Barbosa, R.d.C., Menezes, D.C., Freire, T.F.V. et al. Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent. Mol Biol Rep 39, 4899–4907 (2012). https://doi.org/10.1007/s11033-011-1285-1

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