Abstract
BackgroundCervical cancer is one of the most important cancers in African women. Polymorphisms in the Fas (FasR) and Fas ligand (FasL) genes have been reported to be associated with cervical cancer in certain populations. This study investigated whether these polymorphisms are associated with cervical cancer or human papillomavirus (HPV) infection in South African women.FindingsParticipants were 447 women with invasive cervical cancer (106 black African and 341 women of mixed-ancestry) and 424 healthy women controls, matched by age, (101 black African and 323 women of mixed-ancestry) and domicile (rural or urban). Two polymorphisms in Fas gene (FasR-1377G/A, FasR-670A/G) and one in FasL gene (FasL844T/C) were genotyped by TaqMan. None of the polymorphisms, or the Fas haplotypes, showed a significant association with cervical cancer. There was also no association with HPV infection in the control group. However, on analysis of the control group, highly significant allele, genotype and haplotype differences were found between the two ethnic groups. There were generally low frequencies of FasR-1377A alleles, FasR-670A alleles and FasL-844C alleles in black women compared to the women of mixed-ancestry.ConclusionThis is the first study on the role of Fas and FasL polymorphisms in cervical cancer in African populations. Our results suggest that these SNPs are not associated with cervical cancer in these populations. The allele frequencies of the three SNPs differed markedly between the indigenous African black and mixed-ancestry populations.
Highlights
Cervical cancer is one of the most important cancers in African women
No significant differences in age or HIV status were observed between cases and controls
The two FasR polymorphisms were in tight linkage disequilibrium (LD) (P < 0.05), except in the black controls (P = 0.078)
Summary
Cervical cancer is one of the most important cancers in African women. Polymorphisms in the Fas (FasR) and Fas ligand (FasL) genes have been reported to be associated with cervical cancer in certain populations. This study investigated whether these polymorphisms are associated with cervical cancer or human papillomavirus (HPV) infection in South African women. Cervical cancer is caused by persistent infection with specific types of human papillomavirus (HPV) During their life-time, many women become infected with HPV but most are able to clear the infection and only a small fraction develop cervical cancer. This indicates that additional risk factors play an important role in the development of cervical cancer. An A→G change at Fas-670 reduces the expression of the FasR, by abolishing the Gamma interferon activation signal binding site which results in decreased activation of induced cell death [4,5,6]. It has been shown that the FasL-844C allele is associated with higher basal expression than the -844T allele and that reduced expression of FasL inhibits the apoptotic activity of the FasR-FasL pathway [7]
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