p53 polymorphism in human papillomavirus-associated esophageal cancer.
Human papillomavirus type 16/18 (HPV-16/18) is implicated in the pathogenesis of squamous cell carcinoma (SCC) of the cervix and esophagus. The arginine allele at codon 72 of p53 was found to be more susceptible to degradation by HPV E6 protein than is the proline allele in vivo, thus resulting in a high frequency of cervical SCC in individuals homozygous for arginine at the codon. There are controversial results from several clinical studies of cervical SCC. In the present study, encoding regions of p53 codon 72 and HPV-16/18 E6 were directly sequenced, using pairs of primary esophageal SCC tissue and corresponding normal mucosa, which were from 75 patients (Japanese, n = 38; Chinese, n = 37). The arginine allele alone was detected in 70.6% (12 of 17) of HPV-positive cases but only in 43.1% (25 of 58) of HPV-negative cases (P < 0.05). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. Because our findings between tumor specimens and the normal mucosae differed, we suggest that the frequent loss of proline allele in HPV-associated carcinogenesis of the esophagus major plays some role. The particular type of p53 polymorphism may indicate a potential candidate for HPV-associated SCC.
Kawaguchi
H
H
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan. hideto@surg2.med.kyushu-u.ac.jp
Ohno
S
S
Araki
K
K
Miyazaki
M
M
Saeki
H
H
Watanabe
M
M
Tanaka
S
S
Sugimachi
K
K
D000483:Alleles; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003062:Codon; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000821:virology; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000302:isolation & purification*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA
D003062:Codon; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D001120:Arginine; D011392:Proline