Genetic polymorphisms and cervical cancer development: ATM G5557A and             p53bp1 C1236G.
Persistent infections by high-risk types of human papillomavirus (HPV) have been established as the etiological agent of cervical cancer. The integration of the HPV genome into the host genome is a crucial step in cervical carcinogenesis, although, correct activation of DNA damage repair pathways will avoid the development of cancer. Recent data indicate that several polymorphisms of key regulators from the DNA damage repair pathway (i.e. 53BP1 and ATM) are associated with cancer development susceptibility. We have developed a hospital-based retrospective study considering 429 cervical specimens from women with different cervical lesions including invasive carcinoma. This study aimed to evaluate the role of the ATM D1853N (5557G>A) and 53bp1 D353E (1236C>G) polymorphisms in the development of cervical cancer, using TaqMan SNP Genotyping Assays. Statistical analysis revealed that ATM 5557GG homozygous individuals (OR=1.94; p=0.044) are at increased risk of developing LSIL, while for the 53BP1 1236C>G polymorphism no association was found. Nevertheless, we observed a tendency for an increased risk of LSIL in 53BP1 1236C allele carriers (OR=1.63; p=0.069). Logistic regression adjusted for age revealed no significant differences from the non-adjusted analysis. This is the first study to evaluate the role of ATM G5557A and P53BP1 C1236G polymorphisms in cervical cancer susceptibility. This study reveals a possible trend of both polymorphisms for a genetic susceptibility pattern of cervical cancer development. Hence, our results may be of interest for future understanding of the progression of cervical cancer.
Molecular Oncology Group, Portuguese Institute of Oncology of                     Porto, Rua Dr António Bernardino Almeida, 4200-072 Porto, Portugal.
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S
Oliveira
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J
Ribeiro
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Sousa
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D
Pinto
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I
Baldaque
R
R
Medeiros
D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011174:Portugal; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases