Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma

Hama, Takanori; Norizoe, Chihiro; Saito, Hiroaki; Mimura, Takashi; Kato, Takakuni; Moriyama, Hiroshi; Urashima, Mitsuyoshi

doi:10.1371/journal.pone.0029634

Cited by 26 publications

(26 citation statements)

References 30 publications

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“…As vitamin D metabolism involves many regulatory genes it is not unexpected that the same GSVs would result in the same direction of associations for each disease outcome. Similar results were also found in other studies on cancer outcome18 and risk 40. In one study, VDR sequence variants and haplotypes suggested an association may exist with progression‐free survival in a cohort of Japanese with HNC,18 although the sample size was not large enough to draw definitive conclusions.…”

Section: Discussionsupporting

confidence: 82%

“…However, vitamin D may play a different role in disease initiation compared to disease progression, and GSVs that predict disease outcomes may be different than those that predict disease risk. There are many reports suggesting that vitamin D can reduce tumor growth of HNC in vitro and in vivo 18. Research has shown GSVs in vitamin D metabolism pathway in several cancers could modify the disease outcome.…”

Section: Discussionmentioning

confidence: 99%

“…As vitamin D mediates its functional activity by binding with VDR, most genetic association studies have focused on GSVs in the VDR gene. A number of studies have reported a possible link between GSVs in VDR and altered risk for survival and progression in head and neck,18 breast,19,20 renal21 and prostate22 cancers. Genes that are involved in the regulatory function of vitamin D metabolism pathways may provide insight into the role of these GSVs and vitamin D level in disease outcome.…”

mentioning

confidence: 99%

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Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients

Azad

Bairati

Qiu

et al. 2012

Intl Journal of Cancer

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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. In contrast, lower levels of serum 25(OH)D have been associated with an increased risk of oral cavity and esophageal, 3 colorectal, 4,5 breast, 6 ovarian 7 and prostate 8 cancers. One study found subnormal 25(OH)D (<37.5 nmol/L) in a significant proportion (45%) of patients with head and neck cancer (HNC) in a Finnish population, 9 while other studies found no association of serum vitamin D level with HNC risk 10 and HNC outcome. 11 Inherited genetic sequence variants (GSVs) that also influence the circulating 25(OH)D level could serve as biomarkers to investigate the association of serum vitamin D level with disease outcome. Results from previous twin and family studies suggest that GSVs in common vitamin D metabolism pathway genes may contribute to the variability of vitamin D level. 12,13 Genome-wide association studies have found the regulatory role of GSVs in vitamin D metabolic pathway genes and their association with circulating vitamin D level. 14,15 Furthermore, one study showed that the presence of detrimental Key words: head and neck cancer, serum vitamin D level, genetic sequence variant, overall survival, second primary cancer Additional Supporting Information may be found in the online version of this article.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients

Azad

Bairati

Qiu

et al. 2012

Intl Journal of Cancer

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“…Hama et al reported the VDR FokI TT genotype was associated with a poor progression-free survival rate in patients with head and neck squamous cell carcinoma. In contrast, the other polymorphisms (BsmI, ApaI, and TaqI) showed no significant associations with progression-free survival [35]. In this study, we did not perform prognostic analyses; however, we found that the TT genotype carriage of TaqI polymorphisms was associated with advanced tumor stage, worse tumor differentiation, presence of cirrhosis, and lymph node metastasis.…”

Section: Discussionmentioning

confidence: 60%

The Associated Ion between the VDR Gene Polymorphisms and Susceptibility to Hepatocellular Carcinoma and the Clinicopathological Features in Subjects Infected with HBV

Yao

Zeng

Zhang

et al. 2013

BioMed Research International

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Aim. To evaluate the possible association between the vitamin D receptor (VDR), single-nucleotide polymorphisms (SNPs), and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. Method. 968 chronic HBV infection patients were enrolled, of which 436 patients were diagnosed HCC patients, and 532 were non-HCC patients. The clinicopathological characteristics of HCC were evaluated. The genotypes of VDR gene at FokI, BsmI, ApaI, and TaqI were determined. Results. The genotype frequencies of VDR FokI C>T polymorphism were significantly different between HCC and non-HCC groups. HCC patients had a higher prevalence of FokI TT genotype than non-HCC subjects. With FokI CC as reference, the TT carriage had a significantly higher risk for development of HCC after adjustments with age, sex, HBV infection time, α-fetoprotein, smoking status, and alcohol intake. In addition, we also found that the TT genotype carriage of FokI polymorphisms were associated with advanced tumor stage, presence of cirrhosis, and lymph node metastasis. The SNP at BsmI, ApaI, and TaqI did not show positive association with the risk and clinicopathological features of HCC. Conclusion. The FokI C>T polymorphisms may be used as a molecular marker to predict the risk and to evaluate the disease severity of HCC in those infected with HBV.

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“…We used polymerase chain reaction and direct sequencing to analyze VDR polymorphisms according to the Fok I single nucleotide polymorphisms as described previously [15].…”

Section: Methodsmentioning

confidence: 99%

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

et al. 2012

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BackgroundWe aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.MethodsIn a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.Results1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).ConclusionsThese results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.

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Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma

Cited by 26 publications

References 30 publications

Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients

Genetic sequence variants in vitamin D metabolism pathway genes, serum vitamin D level and outcome in head and neck cancer patients

The Associated Ion between the VDR Gene Polymorphisms and Susceptibility to Hepatocellular Carcinoma and the Clinicopathological Features in Subjects Infected with HBV

Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes

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