The combined risks of reduced or increased function variants in cell death pathway genes differentially influence cervical cancer risk and herpes simplex virus type 2 infection among black Africans and the Mixed Ancestry population of South Africa

BMC Cancer

Research Article

Collet Dandara¹  Koushik Chattopadhyay²  Anna-Lise Williamson³  Annapurna Hazra⁴ 

[1] Division of Human Genetics, Faculty of Health Science, University of Cape Town, Cape Town, Republic of South Africa;Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine (IIDMM), University of Cape Town, Cape Town, Republic of South Africa;Current address: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA;Division of Medical Virology and Institute of Infectious Disease and Molecular Medicine (IIDMM), University of Cape Town, Cape Town, Republic of South Africa;National Health Laboratory Service, Groote Schuur Hospital, Cape Town, Republic of South Africa;School of Statistics and Actuarial Sciences, University of KwaZulu-Natal, Durban, Republic of South Africa;

关键词: Cervical Cancer;    Human Papilloma Virus;    Invasive Cervical Cancer;    Human Papilloma Virus Infection;    Abnormal Cytology;   

DOI  :  10.1186/s12885-015-1678-y

 received in 2014-08-05, accepted in 2015-10-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCervical cancer is one of the most important cancers worldwide with a high incident and mortality rate and is caused by the human papilloma virus (HPV). Among sexually active women who get infected with human papillomavirus (HPV), a small fraction progresses to cervical cancer disease pointing to possible roles of additional risk factors in development of the disease which include host genetic factors and other infections such as HSV-2. Since cellular apoptosis plays a role in controlling the spread of virus-infections in cells, gene variants altering the function of proteins involved in cell death pathways might be associated with the clearing of virus infections. Activity altering polymorphisms in FasR (−1377G > A and -670A > G), FasL (−844 T > C) and CASP8 (−652 6 N ins/del) genes have been shown to alter the mechanism of apoptosis by modifying the level of expression of their correspondent proteins.In the present study, we set out to investigate the combined risks of CASP8, FasR, and FasL polymorphisms in cervical cancer, pre-cancerous lesions, HPV infection and HSV-2 infection.MethodsParticipants were 442 South African women of black African and mixed-ancestry origin with invasive cervical cancer and 278 control women matched by age, ethnicity and domicile status. FasR and FasL polymorphisms were genotyped by TaqMan and CASP8 polymorphism by PCR-RFLP. The results were analysed with R using haplo.stats software version 1.5.2.ResultsCASP8 -652 6 N del + FasR-670A was associated with a reduced risk (P = 0.019, Combined Polymorphism Score (CPS) = −2.34) and CASP8 -652 6 N ins + FasR-1377G was associated with a marginal increased risk (P = 0.047, CPS = 1.99) of cervical cancer among black Africans. When compared within the control group, CASP8 -652 6 N ins + FasR-1377A showed a reduced risk (P = 0.023, CPS = −2.28) of HSV-2 infection in both black African and mixed-ancestry population.ConclusionsOur results show that the combined risks of variants in cell death pathway genes are associated with the cervical cancer as well as the HSV-2 infection in the black African and mixed-ancestry population.

【 授权许可】

CC BY   
© Chattopadhyay et al. 2015