title: Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients.
abstract: Although some studies have reported associations between serum vitamin D level and prognosis in several cancers, others have found associations between genetic sequence variants (GSVs) in the vitamin D metabolism pathway genes and outcomes in various cancers including head and neck cancer (HNC). We comprehensively evaluated the association and interaction of GSVs in vitamin D metabolism pathway genes and their regulatory effects on circulatory serum vitamin D level in HNC outcome. We systemically evaluated the association of 89 tagging and candidate-based GSVs in six major vitamin D metabolism pathway genes (VDR, GC, CYP24A1, CYP27A1, CYP27B1 and CYP2R1) and the circulating serum vitamin D level with overall survival (OS) and second primary cancer (SPC) in 522 Stages I-II radiation-treated patients with HNC. For OS: median follow-up time was 8 years; for SPC, 4.4 years. The most common subsite was the larynx (84%). Three hundred and twelve patients were alive at the end of follow-up for OS. SPCs were diagnosed in 108 patients and were primarily of lung (46%). Serum vitamin D levels were significantly lower in patients carrying the minor alleles of GC:rs4588 and CYP2R1:rs10500804. CYP24A1:rs2296241 was significantly associated with OS and CYP2R1:rs1993116 was with SPC. These two GSVs remained significantly associated after adjusting for serum vitamin D level and important clinical factors. GSVs in the vitamin D metabolism pathway genes were associated with disease outcomes in HNC patients; however, these GSVs are different from those affecting serum vitamin D levels.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Azad
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bairati
authors.forename: Xin
authors.initials: X
authors.lastname: Qiu
authors.forename: Huayi
authors.initials: H
authors.lastname: Huang
authors.forename: Dangxiao
authors.initials: D
authors.lastname: Cheng
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.forename: Francois
authors.initials: F
authors.lastname: Meyer
authors.forename: Araba
authors.initials: A
authors.lastname: Adjei
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate; D014807:Vitamin D / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018167:Receptors, Calcitriol; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System