© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 6, 557,
March 17, 1999
© 1999 Oxford University Press
BRIEF COMMUNICATION |
p53 and Genetic Susceptibility to Cervical Cancer
Affiliation of authors: Gynecology and Breast Research Laboratory, Departments of Surgery, Pathology, and Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY.
Correspondence to: Jeff Boyd, Ph.D., Department of Surgery, Box 201, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.
In a recent report, Storey et al. (1) provide compelling experimental evidence that two common polymorphic variants of the p53 tumor suppressor protein differ in their susceptibility to degradation mediated by the E6 oncoprotein of human papillomavirus (HPV). Specifically, the p53 protein with arginine at codon 72 was shown to be more susceptible to E6-induced degradation in vivo than p53 with proline at codon 72. Remarkably, homozygosity for the allele encoding arginine was found at a significantly higher frequency in the germlines of individuals affected by either of two HPV-associated cancers, squamous carcinoma of the cervix or cutaneous carcinomas in renal transplant recipients, than in the germlines of a control population. Storey et al. conclude that individuals homozygous for the arginine-encoding allele of p53 are seven times more susceptible to HPV-associated cervical tumorigenesis than heterozygotes.
Squamous carcinoma of the uterine cervix is the most common gynecologic cancer encountered worldwide (2), and these data provide the first evidence for a possible genetic susceptibility to this malignancy. Furthermore, given that many sexually active females are transiently infected with HPV (3) and that virtually all squamous carcinomas of the cervix are associated with HPV infection (4), the public health implications of this finding are potentially enormous.
As the numbers of cervical cancer case patients (n=30) and control subjects
(n=41) were rather small and limited the power of the study described above (1), we attempted to confirm these findings in a larger case-control analysis. As
shown in Fig. 1,
genotypes at p53 codon 72 were determined by direct
sequence analysis of DNA from 205 individuals. Case patients consisted of 105 individuals
treated at this institution for pathologically confirmed squamous cell carcinoma of the cervix. To
control for ethnic, geographic, and socioeconomic factors, the control population consisted of
100 gynecology patients also treated at this institution over the same time period, none of whom
had any history of squamous cancers of the reproductive tract or genitalia.
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As shown in Table 1,
the genotype frequencies at p53 codon 72 did
not differ substantially between the two groups of patients studied (two-sided P
= .6, chi-square). Logistic regression analysis indicated that the relative risk of cervical
cancer associated with homozygosity for arginine at p53 codon 72, estimated as an odds ratio,
was 0.7 (95% confidence interval = 0.4-1.3, two-sided P = .3).
Statistical analyses were performed using the StatView software package (SAS Institute, Inc.,
Cary, NC). Notably, the frequency of individuals homozygous for arginine was lower in our
cervical cancer population than in that reported by Storey et al. (1), while
the frequency in our control group was higher, suggesting that those data previously reported
may have represented an artifact of small sample size. In conclusion, our data do not support the
hypothesis that the p53 codon 72 polymorphism represents a genetic susceptibility factor for
squamous carcinoma of the cervix.
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REFERENCES
1 Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 1998; 393:229-34.[CrossRef][Medline]cancerlit;98268776
2 Herrero R. Epidemiology of cervical cancer. J Natl Cancer Inst Monogr 1996;21:1-6.cancerlit;97176249
3
Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural
history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423-8.
4 Wright TC, Ferenczy A, Kurman RJ. Carcinoma and other tumors of the cervix. In: Kurman RJ, editor. Blaustein's pathology of the female genital tract. 4th ed. New York (NY): Springer-Verlag; 1994. p. 279-326.
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