CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women.
BACKGROUND
Cervical cancer, caused by specific oncogenic types of human papillomavirus (HPV), is the second most common cancer in women worldwide. A large number of young sexually active women get infected by HPV but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study investigated the role of CCR2-V64I polymorphism in cervical cancer, pre-cancers and HPV infection in South African women resident in Western Cape. CCR2-V64I polymorphism has been previously reported to influence the progression to cervical cancer in some populations and has also been associated with decreased progression from HIV infection to AIDS.


METHODS
Genotyping for CCR2-V64I was done by PCR-SSP in a case-control study of 446 women (106 black African and 340 mixed-ancestry) with histologically confirmed invasive cervical cancer and 1432 controls (322 black African and 1110 mixed-ancestry) group-matched (1:3) by age, ethnicity and domicile status. In the control women HPV was detected using the Digene Hybrid Capture II test and cervical disease was detected by cervical cytology.


RESULTS
The CCR2-64I variant was significantly associated with cervical cancer when cases were compared to the control group (P = 0.001). Further analysis comparing selected groups within the controls showed that individuals with abnormal cytology and high grade squamous intraepitleial neoplasia (HSIL) did not have this association when compared to women with normal cytology. HPV infection also showed no association with CCR2-64I variant. Comparing SIL positive controls with the cases showed a significant association of CCR2-64I variant (P = 0.001) with cervical cancer.


CONCLUSIONS
This is the first study of the role of CCR2-V64I polymorphism in cervical cancer in an African population. Our results show that CCR2-64I variant is associated with the risk of cervical cancer but does not affect the susceptibility to HPV infection or HSIL in South African women of black and mixed-ancestry origin. This result implies that the role of CCR2 is important in invasive cancer of the cervix but not in HPV infection or in the development of pre-cancers.
Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine (IIDMM), University of Cape Town, Cape Town, Republic of South Africa.
Koushik
K
Chatterjee
Collet
C
Dandara
Margaret
M
Hoffman
Anna-Lise
AL
Williamson
D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics* / Q000276:immunology / Q000821:virology; D054390:Receptors, CCR2 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D013019:South Africa; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology
C515334:CCR2 protein, human; D004279:DNA, Viral; D054390:Receptors, CCR2