Malcolm E K, Baber G B, Boyd J C, Stoler M H
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, USA.
Mod Pathol. 2000 Apr;13(4):373-8. doi: 10.1038/modpathol.3880061.
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.
密码子72处的P53等位基因多态性已被作为宫颈癌发生的一个可能的易感因素进行研究，结果并不一致。斯托里及其同事最近发表了一项有趣的发现，即密码子72处精氨酸等位基因纯合的女性患宫颈癌的风险增加了7倍。这激发了一些独立研究，其中大多数研究未发现宫颈癌与精氨酸纯合性之间存在关联。采用改良的斯托里方法来确定密码子72的等位基因型，对431例经显微切割、福尔马林固定的存档宫颈锥切标本进行了DNA检测，这些标本涵盖了从低度鳞状病变到浸润癌的各种情况。对所有精氨酸纯合子和所有不确定的病例采用另一种独立的限制性片段长度多态性分析方法进行检测，以进行确认和最终的等位基因型判定。仅使用斯托里方法时，逻辑回归分析表明精氨酸纯合性与浸润性疾病之间存在关联（优势比为1.42）。然而，采用联合方法进行准确的等位基因分型时，这种趋势消失了（优势比为1.00），不一致性显然可归因于方法学变量。采用两种独立的方法对密码子72进行等位基因分型，并考虑了先前发表报告中提出的一些问题后，p53密码子72处的精氨酸纯合性与浸润性宫颈癌风险增加无关。
