Source
Department of Otorhinolaryngology-Head and Neck Surgery, Sir Run Run Shaw Hospital, Key Laboratory of Biotherapy of Zhejiang province, Zhejiang University, Hangzhou, China.
Abstract
OBJECTIVE:
Transforming growth factor β1 (TGFβ1) promotes tumor growth and metastasis in the later stage of cancer development. In this study, we explored whether TGFβ1 polymorphisms were associated with increased risk of nasopharyngeal carcinoma (NPC) in a Chinese population.
DESIGN:
Case-control study.
SETTING:
Hospitals of the Department of Otorhinolaryngology-Head and Neck Surgery.
SUBJECTS AND METHODS:
Two single nucleotide polymorphisms of TGFβ1 gene promoter -509C/T (rs1800469) and 869T/C (Leu 10 Pro, rs1800470) at exon 1 were analyzed in 522 NPC patients and 712 age- and sex-matched controls in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Functional relevance of the polymorphism was determined by biochemical assays.
RESULTS:
The -509T allele carriers were associated with a significantly reduced risk of NPC as compared with the noncarriers (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53-0.89 and OR, 0.50; 95% CI, 0.31-0.67, respectively). Moreover, -509C-containing TGFβ1 promoter drove an ~1.7-fold increase in reporter expression, compared with the -509T-containing counterpart in both CNE-1 and CNE-2 cell lines. The TGFβ1 -509 CC genotype carriers had a higher TGFβ1 mRNA level than the TGFβ1 -509TT genotype carriers did (P < .01). However, no significant association was observed between the 869T/C polymorphism and risk of NPC.
CONCLUSION:
These findings indicate that the -509C/T polymorphism in TGFβ1 may play a vital role in mediating individual susceptibility to NPC.