TY - JOUR
T1 - Polymorphisms of the DNMT3B gene and risk of squamous cell carcinoma of the head and neck
T2 - A case-control study
AU - Liu, Zhensheng
AU - Wang, Luo
AU - Wang, Li E.
AU - Sturgis, Erich M.
AU - Wei, Qingyi
N1 - Funding Information:
We thank Margaret Lung, Kathryn Patterson and Leanel Fairly for their assistance in recruiting the subjects; Yawei Qiao for technical assistance; Jianzhong He and Kejin Xu for their laboratory assistance; Monica Domingue for manuscript preparation; and Susan Eastwood for scientific editing. This study was supported by National Institutes of Health Grants ES 11740 (Q. Wei) and in part by CA100264 (Q. Wei) and CA 16672 (The University of Texas M.D. Anderson Cancer Center).
Funding Information:
Grant sponsor: National Institutes of Health Grants ES 11740 (to Q.W.) and CA 16672 (to M.D. Anderson Cancer Center).
PY - 2008/9/8
Y1 - 2008/9/8
N2 - DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been reportedly to be associated with risk of several cancers, but few studies have investigated their roles in squamous cell carcinoma of the head and neck cancer (SCCHN). Here we report a hospital-based case-control study with 832 SCCHN patients and 843 cancer-free controls of non-Hispanic whites that evaluated the association between two DNMT3B single nucleotide polymorphisms (SNPs) DNMT3B -149C>T (rs2424913) and DNMT3B -579G>T (rs2424909) in the promoter region and risk of SCCHN. We found that compared with C-allele carriers, the DNMT3B -149 TT genotype was statistically significantly associated with increased risk of SCCHN (adjusted OR, 1.35, 95% CI, 1.01-1.80, P = 0.043), whereas the DNMT3B -579 TT genotype showed only a non-statistically significant risk compared with G-allele carriers. Further analysis of the effects of combined genotypes suggested that subjects with either DNMT3B -149 TT or DNMT3B -579 TT homozygous genotypes had statistically significantly increased risk of SCCHN (adjusted OR = 1.36, 95% CI = 1.07-1.73, P = 0.013). Stratification analysis showed a more profound risk in the subgroups of the young (≤57 years, the median age of the controls), males, current smokers, current drinkers, and patients with primary tumor sites of pharynx and larynx. This large study provides reliable risk estimates for associations between DNMT3B variants and SCCHN risk in non-Hispanic whites, and our findings are consistent with that of previously reported cancer case-control studies of other cancers. Further mechanistic studies are needed to unravel the underlying molecular mechanisms.
AB - DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been reportedly to be associated with risk of several cancers, but few studies have investigated their roles in squamous cell carcinoma of the head and neck cancer (SCCHN). Here we report a hospital-based case-control study with 832 SCCHN patients and 843 cancer-free controls of non-Hispanic whites that evaluated the association between two DNMT3B single nucleotide polymorphisms (SNPs) DNMT3B -149C>T (rs2424913) and DNMT3B -579G>T (rs2424909) in the promoter region and risk of SCCHN. We found that compared with C-allele carriers, the DNMT3B -149 TT genotype was statistically significantly associated with increased risk of SCCHN (adjusted OR, 1.35, 95% CI, 1.01-1.80, P = 0.043), whereas the DNMT3B -579 TT genotype showed only a non-statistically significant risk compared with G-allele carriers. Further analysis of the effects of combined genotypes suggested that subjects with either DNMT3B -149 TT or DNMT3B -579 TT homozygous genotypes had statistically significantly increased risk of SCCHN (adjusted OR = 1.36, 95% CI = 1.07-1.73, P = 0.013). Stratification analysis showed a more profound risk in the subgroups of the young (≤57 years, the median age of the controls), males, current smokers, current drinkers, and patients with primary tumor sites of pharynx and larynx. This large study provides reliable risk estimates for associations between DNMT3B variants and SCCHN risk in non-Hispanic whites, and our findings are consistent with that of previously reported cancer case-control studies of other cancers. Further mechanistic studies are needed to unravel the underlying molecular mechanisms.
KW - Cancer risk
KW - DNMT3B
KW - Methylation
KW - Molecular epidemiology
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=48149099598&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48149099598&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2008.03.034
DO - 10.1016/j.canlet.2008.03.034
M3 - Article
C2 - 18455294
AN - SCOPUS:48149099598
SN - 0304-3835
VL - 268
SP - 158
EP - 165
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -