The influence of chemokine receptor CCR2 genotypes in the route to cervical carcinogenesis.
Invasive squamous cell carcinomas of the cervix arise from earlier, reversible precursor lesions called low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively). The aim of our study was to analyse the influence of the CCR2-64I polymorphism in the development of SIL due to its preponderant role in the cervical carcinogenesis and in the progression of these lesions to invasive cervical carcinoma. We conducted a case-control study, analyzing 565 Caucasian women from the north of Portugal. The CCR2-64I polymorphism was analysed through polymerase chain reaction followed by restriction fragment length polymorphism. The frequency of GG, GA and AA genotypes was 76.5, 23.5 and 0.0% respectively, in HSIL patients, and 87.8, 11.1 and 1.1% respectively, in the control group. The G allele frequency was 88.2% in the HSIL group and 93.4% in the control group. Regarding the A allele frequency, it was 11.8% in the HSIL group and 6.6% in the control group. Overall, the frequency of A carrier genotypes was higher in HSIL patients than in the control group (p = 0.013; OR = 2.21; 95%CI: 1.17-4.15), suggesting that CCR2-64I polymorphism might contribute to the establishment of HSIL, through the disruption of the naturally fragile immune response directed towards human papillomavirus infection.
Coelho
Ana
A
Molecular Oncology/Virology, Instituto Português de Oncologia, Porto, Portugal.
Matos
Ana
A
Catarino
Raquel
R
Pinto
Daniela
D
Sousa
Hugo
H
Pereira
Deolinda
D
Medeiros
Rui
R
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011174:Portugal; D054390:Receptors, CCR2 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
C515334:CCR2 protein, human; D054390:Receptors, CCR2