Single nucleotide polymorphism at alcohol dehydrogenase-1B is associated with risk of esophageal squamous cell carcinoma.
BACKGROUND
Esophageal squamous incidence in many developed countries has increased dramatically over last decades, while the underlying mechanism of the biogenesis of ES was still unknown.


METHODS
Here, we investigate 1001 subjects with esophageal cancer recruited from the affiliated hospital of Shanghai Jiao Tong University from Jan. 1, 2001 to Feb. 2, 2004. Single nucleotide polymorphism (SNP) of alcohol dehydrogenase-1B (ADH1B) was performed, and the recombinant plasimd containing ADH1B was constructed. Then, the ADH1B was purified and the enzymatic activity was assayed according to the methodology of Quayle. Furthermore, the effect of ADH1B on proliferation of human esophageal squamous cell lines was determined and the underlying mechanism of ADH1B was investigated.


RESULTS
Logistic regression analyses revealed that subjects carrying the GG variant homozygote had a significant 2.81-fold (adjusted OR = 2.81; 95% CI = 2.18-3.62) increased risk of esophageal cancer. We found that SNP of ADH1B (GG) significantly promotes cell proliferation in ESGG. ADH1B (GG) could down-regulate endogenous ADH1B expression at posttranscriptional level. Moreover, re-expression of ADH1B in cells transfected with ADH1B (AA) significantly inhibits cell proliferation.


CONCLUSIONS
Our data implied that ADH1B (GG) could promote cell proliferation in human ESGG through regulating the enzyme activity of ADH1B. Therefore, we propose that ADH1B might be used as a therapeutic agent for human ESGG.
Bo
B
Ye
Chun-Yu
CY
Ji
Yi
Y
Zhao
Wang
W
Li
Jian
J
Feng
Department of Thoracic Surgery, The Second Affiliated Hospital of Dalian Medical University, Zhongshan Road 467, Dalian, Liaoning 116023, China. zhangxuwy@hotmail.com.
Xu
X
Zhang