title: Association of methylenetetrahydrofolate reductase polymorphism and the risk of squamous cell carcinoma in renal transplant patients.
abstract: The relative risk of developing cutaneous squamous cell carcinoma (SCC) is significantly increased after organ transplantation. We investigated the genetic association of SCC in two pathways associated with cancer risks, with the potential for modification by vitamin supplementation. A total of 367 renal transplant recipients (117 with SCC and 250 without any skin cancer) were genotyped for key polymorphisms in the folate pathway (methylene tetrahydrofolate reductase; MTHFR:C677T), and the vitamin D pathway (vitamin D receptor: Intron8G/T;). Individuals carrying the MTHFR 677T allele had a marked increase in risk of SCC (adjusted odds ratio=2.54, P=0.002, after adjustment for age, ender, skin type, sun exposure score, and immunosuppression duration; lower 95% confidence boundary odds ratio of 1.41). In contrast, vitamin D receptor polymorphisms were not significantly associated. Folate-sensitive pathways may play a critical role in the elevated rate of SCC in renal transplant recipients.
authors.affiliation: Department of Dermatology, Beaumont Hospital, Dublin, Ireland. mrylaing@yahoo.co.uk
authors.forename: Mary E
authors.initials: ME
authors.lastname: Laing
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: Moloney
authors.forename: Wen L
authors.initials: WL
authors.lastname: Ho
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Murphy
authors.forename: Peter
authors.initials: P
authors.lastname: Conlon
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
authors.forename: Denis C
authors.initials: DC
authors.lastname: Shields
mesh_terms: D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003596:Cytosine; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006801:Humans; D007438:Introns; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics; D012306:Risk; D012878:Skin Neoplasms / Q000235:genetics*; D013941:Thymine
chemical_list: D018167:Receptors, Calcitriol; D006147:Guanine; D003596:Cytosine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine