Oncogenic virus-associated neoplasia: a role for cyclin D1 genotypes influencing the age of onset of disease?
Cyclin D1 (CCND1) is a key regulatory protein at the G1/S checkpoint of the cell cycle. The purpose of our study was to assess the role of CCND1 genotypes influencing the age of onset of oncogenic virus-associated neoplasia. We conducted a hospital-based case-control study of 581 individuals, including 247 controls and 334 cases (108 nasopharyngeal and 226 cervical cancer cases). The polymorphism analysis was performed in blood samples by PCR-RFLP methodology. Age-adjusted logistic regression analysis indicates that individuals carrying two G-alleles have an increased genetic susceptibility for the development of oncogenic virus-associated cancers (aOR=2.02, 95% CI 1.30-3.14, P=0.002). Moreover, our results indicate that the waiting time for onset of oncogenic virus-associated neoplasia in patients homozygous (GG) for CCND1 genotypes (52 years) was 12 years earlier in comparison with patients carrying AG or AA genotypes (60 years) (log-rank test: P=0.0003). Our results may be important in contributing to a more extensive knowledge of the mechanisms involved in oncogenic virus-associated carcinogenesis, as CCND1 may be an important target for the development of new strategies for cancer treatment and prevention.
Catarino
R
R
Molecular Oncology Group and Virology Laboratory, Portuguese Institute of Oncology, Porto, Portugal.
Pereira
D
D
Breda
E
E
Coelho
A
A
Matos
A
A
Lopes
C
C
Medeiros
R
R
D017668:Age of Onset; D016022:Case-Control Studies; D002472:Cell Transformation, Viral / Q000235:genetics*; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology*; D009858:Oncogenic Viruses / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*
D056741:Cyclin D; D016213:Cyclins