p53 codon 72 polymorphism and various human papillomavirus 16 E6 genotypes are risk factors for cervical cancer development.
Risk factors other than human papillomavirus (HPV) infection per se for cervical cancer development have been investigated recently. It was suggested that HPV 16 E6 variants and the p53 codon 72 arginine polymorphism could be progression markers. Indeed, it has been demonstrated that specific E6 variants and p53 arginine were both enriched in cancer. However, especially with regard to the latter, divergent results have been reported. Our aim was thus to investigate whether p53 arginine is important for cervical carcinogenesis by scaling up samples of the two European cohorts, the initial results of which were reported previously. In addition, we have assessed the occurrence of p53 codon 72 arginine, in combination with specific HPV 16 E6 genotypes. We found p53 arginine to be increased in cancer of both cohorts, consistent with our previous concept. Although specific E6 genotypes increased gradually with the severity of the lesion, p53 arginine was enriched in cancer only. Moreover, the frequency of the arginine allele was similar in groups with different E6 genotypes. It is concluded that p53 arginine is a risk factor for cervical cancer but probably acts independently of E6 variants.
Zehbe
I
I
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Voglino
G
G
Wilander
E
E
Delius
H
H
Marongiu
A
A
Edler
L
L
Klimek
F
F
Andersson
S
S
Tommasino
M
M
D001120:Arginine / Q000235:genetics; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D009361:Neoplasm Invasiveness; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins; D012307:Risk Factors; D013548:Sweden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology* / Q000821:virology
D003062:Codon; D004273:DNA, Neoplasm; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D001120:Arginine