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1.  Association between a Functional Polymorphism (-1195T>C) in the IGFBP5 Promoter and Head and Neck Cancer Risk 
Head & neck  2010;33(5):650-660.
No studies have evaluated roles of insulin-like growth factor binding protein 5 (IGFBP-5) polymorphisms in risk of squamous cell carcinoma of the head and neck (SCCHN).
A hospital-based study of 1082 SCCHN patients and 1120 cancer-free controls was performed to investigate associations between two functional polymorphisms -1195T>C and -709G>C in the IGFBP5 promoter region and SCCHN risk.
We demonstrated that the transcription factor AP-1 differentially bound to T or C variants at -1195 in the promoter to regulate the IGFBP5 promoter activity and that the C variant genotypes were associated with deferential risk of late-stage SCCHN, compared with the TT genotype, particularly for HPV-unrelated sites (adjusted OR, 2.21; 95% CI, 1.19-4.11 for CC vs. TT).
The IGFBP5 -1195T>C polymorphism is functional and may potentially be a biomarker for susceptibility to late-stage SCCHN.
PMCID: PMC3023825  PMID: 20949447
IGFBP5; head neck cancer; TNM stage; polymorphism; association
2.  A novel functional DEC1 promoter polymorphism −249T>C reduces risk of squamous cell carcinoma of the head and neck 
Carcinogenesis  2010;31(12):2082-2090.
Human DEC1 (deleted in esophageal cancer 1) gene is located on chromosome 9q, a region frequently deleted in various types of human cancers, including squamous cell carcinoma of the head and neck (SCCHN). However, only one epidemiological study has evaluated the association between DEC1 polymorphisms and cancer risk. In this hospital-based case–control study, four potentially functional single-nucleotide polymorphisms −1628 G>A (rs1591420), −606 T>C [rs4978620, in complete linkage disequilibrium with −249T>C (rs2012775) and −122 G>A(rs2012566)], c.179 C>T p.Ala60Val (rs2269700) and 3′ untranslated region-rs3750505 as well as the TP53 tumor suppressor gene codon 72 (Arg72Pro, rs1042522) polymorphism were genotyped in 1111 non-Hispanic Whites SCCHN patients and 1130 age-and sex-matched cancer-free controls. After adjustment for age, sex and smoking and drinking status, the variant −606CC (i.e. −249CC) homozygotes had a significantly reduced SCCHN risk (adjusted odds ratio = 0.71, 95% confidence interval = 0.52–0.99) compared with the −606TT homozygotes. Stratification analyses showed that a reduced risk associated with the −606CC genotype was more pronounced in subgroups of non-smokers, non-drinkers, younger subjects (defined as ≤57 years), carriers of the TP53 Arg/Arg (rs1042522) genotype, patients with oropharyngeal cancer or late-stage SCCHN. Further in silico analysis revealed that the −249 T-to-C change led to a gain of a transcription factor-binding site. Additional functional analysis showed that the −249T-to-C change significantly enhanced transcriptional activity of the DEC1 promoter and the DNA–protein-binding activity. We conclude that the DEC1 promoter −249 T>C (rs2012775) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites.
PMCID: PMC2994282  PMID: 20935061
3.  The functional IGFBP7 promoter −418G>A polymorphism and Risk of Head and Neck Cancer 
Mutation research  2010;702(1):32-39.
Insulin-like growth factor binding protein 7 (IGFBP7) functions mostly independent of the IGF signaling pathway and acts as a tumor suppressor in multiple cancers, but roles of IGFBP7 genetic variants in cancer remains unknown. In a hospital-based study of 1,065 patients with squamous cell carcinoma of head and neck (SCCHN) and 1,112 cancer-free controls of non-Hispanic whites, we investigated associations between two putatively functional IGFBP7 promoter single nucleotide polymorphisms (SNPs) (−702G>C, rs11573014 and −418G>A, rs4075349) and SCCHN risk. A significantly lower SCCHN risk was observed in those subjects carrying −418AG (adjusted OR=0.82, 95% CI=0.67–0.99) and −418AG+AA (adjusted OR=0.82, 95% CI=0.69–0.99) genotypes than those carrying the −418GG genotype, but not for the −702G>C SNP. However, those subjects carrying two common homozygous genotypes of these two SNPs (−418GG and −702GG) had an increased risk (adjusted OR=1.21, 95% CI=1.00-0.1.46) than did those carrying variant genotypes (−418AG+AA and −702CG+CC). This increased risk was more evident in subgroups of never smokers and subjects with oral cancer. Further functional analysis showed that the IGFBP7 −418A allele had significantly higher promoter and DNA-protein binding activities than did the G allele, suggesting a tumor suppressor role of this allelic change in the SCCHN etiology. We conclude that the functional variant −418 G>C in the IGFBP7 promoter is associated with reduced risk of SCCHN, likely by enhancing the IGFBP7 promoter and DNA-protein binding activities. Larger studies are needed to validate our findings.
PMCID: PMC2939148  PMID: 20599521
IGFBP7; case-control study; tumor suppressor gene; head and neck cancer; promoter polymorphism
4.  Genetic polymorphisms in the PTPN13 gene and risk of squamous cell carcinoma of head and neck 
Carcinogenesis  2009;30(12):2053-2058.
Fas-associated phosphatase-1 is encoded by the protein tyrosine phosphatase, non-receptor type 13 (PTPN13) gene and attributes to the resistance to Fas-mediated apoptosis in several tumors, including squamous cell carcinoma of the head and neck (SCCHN). However, no epidemiological studies have investigated the roles of PTPN13 polymorphisms in SCCHN risk. In this hospital-based case–control study of 1069 SCCHN patients and 1102 non-Hispanic white cancer-free controls, we evaluated the associations between three single-nucleotide polymorphisms c.4068 T>G F1356L (rs10033029), c.4566 A>G I1522M (rs2230600) and c.6241 T>G Y2081D (rs989902) located in the coding region of PTPN13 and SCCHN risk. We found that a significantly increased SCCHN risk was associated with the c.4566 I1522M GG genotype [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.27–2.79] and c.6241 Y2081D GT genotype (OR, 1.26; 95% CI, 1.03–1.53) compared with the c.4566 I1522M AA and c.6241 Y2081D TT genotypes, respectively. Further stratified analyses showed that risk associated with the c.4566 I1522M GG genotype was more profound in the subgroups of young (≤57 years), males, never smokers, current drinkers and patients with pharyngeal cancer; that risk associated with c.6241 Y2081D GT genotype persisted in subgroups of old (>57 years), males, current drinkers and patients with pharyngeal and laryngeal cancers and that risk associated with c.6241 Y2081D GG genotype was borderline in patients with laryngeal cancer. In conclusion, polymorphisms in the PTPN13 coding region may be biomarkers for susceptibility to SCCHN in USA populations.
PMCID: PMC2792321  PMID: 19892796

Results 1-4 (4)