细胞死亡途径基因功能变体减少或增加的综合风险，对非洲黑人及南非混合血统人群的宫颈癌风险和2型单纯疱疹病毒感染有不同影响。
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.
作者信息
Chattopadhyay Koushik, Williamson Anna-Lise, Hazra Annapurna, Dandara Collet
机构信息
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.
出版信息
BMC Cancer. 2015 Oct 12;15:680. doi: 10.1186/s12885-015-1678-y.
BACKGROUND
Cervical 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.
METHODS
Participants 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.
RESULTS
CASP8 -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.
CONCLUSIONS
Our 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.
背景
宫颈癌是全球最重要的癌症之一，发病率和死亡率都很高，由人乳头瘤病毒（HPV）引起。在感染人乳头瘤病毒（HPV）的性活跃女性中，一小部分会发展为宫颈癌，这表明其他风险因素在该疾病的发生中可能起作用，这些因素包括宿主遗传因素和其他感染，如单纯疱疹病毒2型（HSV - 2）。由于细胞凋亡在控制病毒在细胞内的传播中起作用，改变参与细胞死亡途径的蛋白质功能的基因变异可能与病毒感染的清除有关。FasR（-1377G＞A和-670A＞G）、FasL（-844T＞C）和CASP8（-652 6N ins/del）基因中改变活性的多态性已被证明可通过改变其相应蛋白质的表达水平来改变细胞凋亡机制。在本研究中，我们着手调查CASP8、FasR和FasL基因多态性在宫颈癌、癌前病变、HPV感染和HSV - 2感染中的综合风险。
方法
参与者为442名患有浸润性宫颈癌的南非黑人非洲裔和混血裔女性以及278名按年龄、种族和居住状况匹配的对照女性。FasR和FasL基因多态性通过TaqMan进行基因分型，CASP8基因多态性通过PCR - RFLP进行检测。使用R软件，通过haplo.stats软件版本1.5.2对结果进行分析。
结果
在黑人非洲裔人群中，CASP8 -652 6N del + FasR -670A与宫颈癌风险降低相关（P = 0.019，联合多态性评分（CPS）=-2.34），而CASP8 -652 6N ins + FasR -1377G与宫颈癌风险略有增加相关（P = 0.047，CPS = 1.99）。在对照组中进行比较时，CASP8 -652 6N ins + FasR -1377A在黑人非洲裔和混血裔人群中均显示HSV - 2感染风险降低（P = 0.023，CPS = -2.28）。
结论
我们的结果表明，细胞死亡途径基因变异的综合风险与黑人非洲裔和混血裔人群中的宫颈癌以及HSV - 2感染相关。
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