BACKGROUND: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area. METHODS: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN). Controls were women without a history of cervical abnormalities. From each woman, we obtained a cervical specimen for HPV testing and p53 genotyping, and a questionnaire was completed. DNA sequencing was used to minimize genotype misclassification. A subsample of specimens was also genotyped using the TaqMan assay. RESULTS: There were 357 cases and 760 controls recruited between February 2001 and December 2003. The distribution of Arg/Arg, Arg/Pro and Pro/Pro was 55.2, 36.4 and 8.4%, respectively, among cases, and 52.1, 38.7 and 9.2%, among controls, corresponding to an odds ratio (OR) adjusted for ancestral origin of 1.16 (95% confidence interval (CI): 0.9-1.5) for Arg/Arg versus other genotypes. When restricted to high-risk HPV-positive women, the adjusted ORs were 1.40 (CI: 0.9-2.1) and 2.12 (CI: 1.1-4.2), for Arg/Arg versus other genotypes and versus Pro/Pro, respectively. The findings were comparable with analyses of genotype results that agreed between DNA sequencing and TaqMan. CONCLUSIONS: In this study, we attempted to minimize selection bias, population stratification and genotype misclassification. The results suggest that the role of the p53 codon 72 polymorphism on HGCIN is weak at best. Further research may reveal if the polymorphism has a stronger influence on the risk of invasive cervical cancer.
BACKGROUND: The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated in increasing susceptibility of the cervix to human papillomavirus (HPV) infection and thus altering cancer risk. However, research on this topic has been contentious, which prompted us to carry out a case-control study in the Montreal area. METHODS: Cases were women with histologically-confirmed high-grade cervical intraepithelial neoplasia (HGCIN). Controls were women without a history of cervical abnormalities. From each woman, we obtained a cervical specimen for HPV testing and p53 genotyping, and a questionnaire was completed. DNA sequencing was used to minimize genotype misclassification. A subsample of specimens was also genotyped using the TaqMan assay. RESULTS: There were 357 cases and 760 controls recruited between February 2001 and December 2003. The distribution of Arg/Arg, Arg/Pro and Pro/Pro was 55.2, 36.4 and 8.4%, respectively, among cases, and 52.1, 38.7 and 9.2%, among controls, corresponding to an odds ratio (OR) adjusted for ancestral origin of 1.16 (95% confidence interval (CI): 0.9-1.5) for Arg/Arg versus other genotypes. When restricted to high-risk HPV-positive women, the adjusted ORs were 1.40 (CI: 0.9-2.1) and 2.12 (CI: 1.1-4.2), for Arg/Arg versus other genotypes and versus Pro/Pro, respectively. The findings were comparable with analyses of genotype results that agreed between DNA sequencing and TaqMan. CONCLUSIONS: In this study, we attempted to minimize selection bias, population stratification and genotype misclassification. The results suggest that the role of the p53 codon 72 polymorphism on HGCIN is weak at best. Further research may reveal if the polymorphism has a stronger influence on the risk of invasive cervical cancer.
Authors: Joseph E Tota; Agnihotram V Ramanakumar; Luisa L Villa; Harriet Richardson; Ann N Burchell; Anita Koushik; Marie-Hélène Mayrand; François Coutlée; Eduardo L Franco Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-10-02 Impact factor: 4.254
Authors: Andrea C Tricco; Carmen H Ng; Vladimir Gilca; Andrea Anonychuk; Ba' Pham; Shirra Berliner Journal: BMC Infect Dis Date: 2011-09-05 Impact factor: 3.090
Authors: Adriana C Vidal; Susan K Murphy; Brenda Y Hernandez; Brandi Vasquez; John A Bartlett; Olola Oneko; Pendo Mlay; Joseph Obure; Francine Overcash; Jennifer S Smith; Mike van der Kolk; Cathrine Hoyo Journal: Infect Agent Cancer Date: 2011-11-14 Impact factor: 2.965
Authors: Joseph E Tota; Mengzhu Jiang; Agnihotram V Ramanakumar; Stephen D Walter; Jay S Kaufman; François Coutlée; Harriet Richardson; Ann N Burchell; Anita Koushik; Marie Hélène Mayrand; Luisa L Villa; Eduardo L Franco Journal: PLoS One Date: 2016-12-22 Impact factor: 3.240
Authors: Helen Trottier; Marie-Hélène Mayrand; François Coutlée; Patricia Monnier; Louise Laporte; Joseph Niyibizi; Ana-Maria Carceller; William D Fraser; Paul Brassard; Jacques Lacroix; Diane Francoeur; Marie-Josée Bédard; Isabelle Girard; François Audibert Journal: Papillomavirus Res Date: 2016-07-12