Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women.
The WAF1 gene, located on chromosome 6p21.2, has been cloned and identified as a p53 mediator and an inhibitor of G1 cyclin-dependent kinases (CDKs). The present study was performed to investigate the possible role of the WAF1 gene in the pathogenesis of human cervical carcinoma. Matched venous blood and cancer tissues from 66 patients with cervical cancer were screened for WAF1 mutation by reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. A polymorphism in the WAF1 gene involving a cytosine (C) to an adenine (A) transversion at the third base of codon 31 was observed in 52 of 66 (78.8%) patients with cervical carcinoma and 68 of 108 (63%) normal individuals (P=0.02). A total of 7 patients (10.6%) were found to have a change of the WAF1 gene at codon 31 on comparison of blood and tumor specimens. An A-->C transversion in 5 tumors and a C-->A transversion in 2 tumors, that were not found in matching normal specimens, were observed. In addition, the presence of loss of heterozygosity (LOH) on chromosome 6p21.2 in tumor and normal tissue DNA were analyzed by PCR at three polymorphic microsatellite loci (D6S276, D6S1624, D6S1583). In two cases, there was a change of Arg/Ser in blood to Ser/Ser in the tumor, which did not involve LOH on 6p21.2. Therefore, somatic mutation of the WAF1 gene was detected in 3% (2 of 66) of patients with cervical cancer in this series. In conclusion, the increased frequency of WAF1 polymorphism in the patients studied implied that codon 31 Arg allele of the WAF1 gene may be associated with a tendency to develop cervical carcinoma. To our knowledge, this is the first report of WAF1 somatic mutations in primary human cervical cancer.
Harima
Y
Y
Department of Radiology, Kansai Medical University, Moriguchi City, Osaka 570-8507, Japan. harima@takii.kmu.ac.jp
Sawada
S
S
Nagata
K
K
Sougawa
M
M
Ostapenko
V
V
Ohnishi
T
T
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004791:Enzyme Inhibitors; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D019656:Loss of Heterozygosity; D011110:Polymorphism, Genetic; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D004247:DNA