TY - JOUR
T1 - Polymorphisms in the MTHFR and VDR genes and skin cancer risk
AU - Han, Jiali
AU - Colditz, Graham A.
AU - Hunter, David J.
N1 - Funding Information:
The authors thank Dr Hardeep Ranu, Craig Labadie, and Pati Soule for their laboratory assistance, Carolyn Guo for her programming support. The authors also thank the participants in the Nurses’ Health Study for their dedication and commitment. This work is supported by NIH grants CA113100 and CA87969. J.H. is partially supported by the Harvard SPORE in Skin Cancer.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33847288858&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgl156
DO - 10.1093/carcin/bgl156
M3 - Article
C2 - 16950800
AN - SCOPUS:33847288858
VL - 28
SP - 390
EP - 397
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 2
ER -