Polymorphism at codon 72 of p53 is not associated with cervical cancer risk.
P53 allelic polymorphism at codon 72 has been studied as a possible predisposing factor for cervical carcinogenesis with inconsistent results. Storey and colleagues recently published the interesting finding of a 7-fold increased risk for cervical cancer in women homozygous for the arginine allele at codon 72. This stimulated a number of independent investigations, the majority of which found no association of cervical cancer and arginine homozygosity. With the use of a modified Storey method for determining codon 72 allelotypes, DNA was examined from 431 microdissected, formalin-fixed, archival cervical conization specimens ranging from low-grade squamous lesions to invasive cancer. An alternative independent method using restriction fragment length polymorphism analysis was performed on all arginine homozygotes and all indeterminate cases for confirmation and final allelotype assignment. With the use of Storey's method alone, logistic regression suggested an association (odds ratio, 1.42) between arginine homozygosity and invasive disease. However, with the use of the combined method for accurate allelotyping, this trend disappeared (odds ratio, 1.00), the discordance was clearly resolvable as being due to methodologic variables. With the use of two separate methods for codon 72 allelotyping and accounting for a number of the issues raised in previously published reports, there is no increased risk for invasive cervical cancer associated with arginine homozygosity at codon 72 of p53.
Malcolm
E K
EK
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, USA.
Baber
G B
GB
Boyd
J C
JC
Stoler
M H
MH
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000483:Alleles; D001120:Arginine / Q000235:genetics; D002278:Carcinoma in Situ / Q000235:genetics / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D003062:Codon / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D003062:Codon; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D001120:Arginine