TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies

Stefanie J. Klug, Meike Ressing, Jochem Koenig, Martin C. Abba, Theodoros Agorastos, Sylvia MF Brenna, Marco Ciotti, BR R. Das, Annarosa Del Mistro, Aleksandra Dybikowska, Anna R. Giuliano, Zivile Gudleviciene, Ulf Gyllensten, Andrea LF Haws, Aslaug Helland, C. Simon Herrington, Alan Hildesheim, Olivier Humbey, Sun H. Jee, Jae Weon KimMargaret M. Madeleine, Joseph Menczer, Hextan YS Ngan, Akira Nishikawa, Yoshimitsu Niwa, Rosemary Pegoraro, MR R. Pillai, Gulielmina Ranzani, Giovanni Rezza, Adam N. Rosenthal, Susanta Roychoudhury, Dhananjaya Saranath, Virginia M. Schmitt, Sharmila Sengupta, Wannapa Settheetham-Ishida, Hiroshi Shirasawa, Peter JF Snijders, Mark H. Stoler, Angel E. Suárez-Rincón, Krisztina Szarka, Ruth Tachezy, Masatsugu Ueda, Ate GJ van der Zee, Magnus von Knebel Doeberitz, Ming Tsang Wu, Tsuyoshi Yamashita, Ingeborg Zehbe, Maria Blettner

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. Methods: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. Findings: The pooled estimates (OR) for invasive cervical cancer were 1·22 (95% CI 1·08-1·39) for arginine homozygotes compared with heterozygotes, and 1·13 (0·94-1·35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1·71 [1·21-2·42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1·35 [1·15-1·58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1·39 [1·13-1·73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1·06 [0·87-1·29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1·06 [0·87-1·29] for arginine homozygotes compared with heterozygotes). Interpretation: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. Funding: German Research Foundation (DFG).

Original languageEnglish
Pages (from-to)772-784
Number of pages13
JournalThe Lancet Oncology
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2009

ASJC Scopus subject areas

  • Oncology

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