[The risk of esophageal squamous cell carcinoma associated with microsatellite polymorphism in promoter of heme oxygenase-1].
OBJECTIVE
To investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population.


METHODS
The (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 ± 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (≥30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by χ2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance.


RESULTS
Higher frequencies of L-allele (25. 8% vs. 14. 9%, χ2 = 9. 520, P = 0. 002), L-allele carrier (41. 3% vs. 27. 6%, χ2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, χ = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, χ2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002).


CONCLUSIONS
The long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis.
Bingchuan
B
Hu
Jian
J
Zhang
Ji
J
Wang
Chengchu
C
Zhu
Baofu
B
Chen
Min
M
Kong
Bo
B
Zhang
Min
M
Zhu
D000483:Alleles; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005787:Gene Frequency; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide; D008207:Lymphatic Metastasis; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014162:Transfection
D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1