TY - JOUR
T1 - A novel functional DEC1 promoter polymorphism - 2249T>C reduces risk of squamous cell carcinoma of the head and neck
AU - Huang, Yu Jing
AU - Niu, Jiangong
AU - Wei, Sheng
AU - Yin, Ming
AU - Liu, Zhensheng
AU - Wang, Li E.
AU - Sturgis, Erich M.
AU - Wei, Qingyi
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgq198
DO - 10.1093/carcin/bgq198
M3 - Article
C2 - 20935061
AN - SCOPUS:78649790003
SN - 0143-3334
VL - 31
SP - 2082
EP - 2090
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -