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Carcinogenesis Advance Access published online on August 31, 2006
Carcinogenesis, doi:10.1093/carcin/bgl156
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received June 25, 2006
Revised August 10, 2006
Accepted August 18, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Polymorphisms in the MTHFR and VDR genes and skin cancer risk

Jiali Han 1 *, Graham A. Colditz 2, and David J. Hunter 3

1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; The Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA
2 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA; The Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115, USA

* To whom correspondence should be addressed.
Jiali Han, E-mail: jiali.han{at}channing.harvard.edu


  Abstract

Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both nutrients are implicated in skin carcinogenesis. We evaluated genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) and the vitamin D receptor (VDR) gene (Fok1, Bsm1, and Cdx2) with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. No significant associations were observed for the two MTHFR polymorphisms on skin cancer risk. We observed an interaction between the C677T polymorphism and total folate intake on SCC risk (P, interaction=0.04); the highest risk was observed among women with TT genotype and low folate intake (OR=2.14; 95%CI=1.01-4.50). The VDR Bsm1 BB genotype was significantly associated with an increased SCC risk (OR=1.51; 95%CI=1.00-2.28). An interaction between the Bsm1 polymorphism and total vitamin D intake on SCC was observed, with the highest risk seen in women with the BB genotype and high vitamin D intake (OR=2.38; 95%CI=1.22-4.62) (P, interaction=0.08). This study suggests a possible role of the polymorphisms in MTHFR and VDR interacting with dietary intakes of folate and vitamin D in skin cancer development, especially for SCC. Due to a large number of comparisons and tests, the possible associations should be interpreted with caution and confirmed by other studies.


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