Zou Jian, Cao Zhu, Zhang Jianyang, Chen Tingting, Yang Shizhou, Huang Yongjie, Hong Die, Li Yang, Chen Xiaojing, Wang Xinyu, Cheng Xiaodong, Lu Weiguo, Xie Xing
The Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.
Oncotarget. 2016 Jun 28;7(26):40135-40147. doi: 10.18632/oncotarget.9510.
Human papillomavirus (HPV) infects cervical epithelial cells through cellular membrane receptors, and then induces the initiation and progression of cervical cancer. Single nucleotide polymorphisms (SNPs) may impact the susceptibility and outcome of diseases, but it's still unknown whether variant in HPV receptor and associated genes is associated with type-specific HPV infection and cervical lesion progression. We examined 96 SNPs in 8 genes which may participate in the HPV infection process in 875 samples with HPV negative or single HPV16, 18, 52, 58 positive from 3299 cervical exfoliated cell samples, by Illumina BeadXpress VeraCode platform, and analyzed the correlation between the SNPs and type-specific HPV infection and cervical lesions progression. We found rs28384376 in EGFR and rs12034979 in HSPG2 significantly correlated to HPV16 infection; rs2575738, rs2575712, rs2575735 in SDC2 and rs6697265 in HSPG2 significantly correlated to HPV18 infection; rs10510097 in FGFR2, rs12718946 in EGFR significantly correlated to HPV52 infection; rs4947972 in EGFR, rs2981451 in FGFR2, rs2575735 in SDC2 significantly correlated to HPV58 infection. And rs3135772, rs1047057 and rs2556537 in FGFR2, rs12034979 in HSPG2, rs16894821 in SDC2 significantly correlated to cervical lesion progression induced by HPV16 infection; rs6697265 and rs6680566 in HSPG2, rs16860426 in ITGA6 by HPV18 infection; rs878949 in HSPG2, rs12718946 and rs12668175 in EGFR by HPV52 infection; no SNP by HPV58 infection. Our findings suggest that HPV receptor and associated gene variants may influence the susceptibilities to HPV type-specific infection and cervical lesion progression, which might have a potential application value in cervical cancer screening and therapy.
人乳头瘤病毒（HPV）通过细胞膜受体感染宫颈上皮细胞，进而诱发宫颈癌的发生与发展。单核苷酸多态性（SNP）可能会影响疾病的易感性和转归，但HPV受体及相关基因的变异是否与特定型别HPV感染及宫颈病变进展相关仍不清楚。我们通过Illumina BeadXpress VeraCode平台，对来自3299份宫颈脱落细胞样本中的875份HPV阴性或单一HPV16、18、52、58阳性样本的8个可能参与HPV感染过程的基因中的96个SNP进行了检测，并分析了这些SNP与特定型别HPV感染及宫颈病变进展之间的相关性。我们发现，EGFR基因中的rs28384376和HSPG2基因中的rs12034979与HPV16感染显著相关；SDC2基因中的rs2575738、rs2575712、rs2575735以及HSPG2基因中的rs6697265与HPV18感染显著相关；FGFR2基因中的rs10510097、EGFR基因中的rs12718946与HPV52感染显著相关；EGFR基因中的rs4947972、FGFR2基因中的rs2981451、SDC2基因中的rs2575735与HPV58感染显著相关。并且，FGFR2基因中的rs3135772、rs1047057和rs2556537，HSPG2基因中的rs12034979，SDC2基因中的rs16894821与HPV16感染所致的宫颈病变进展显著相关；HSPG2基因中的rs6697265和rs6680566，ITGA6基因中的rs16860426与HPV18感染相关；HSPG2基因中的rs878949，EGFR基因中的rs12718946和rs12668175与HPV52感染相关；HPV58感染未发现相关SNP。我们的研究结果表明，HPV受体及相关基因变异可能影响对HPV特定型别感染的易感性及宫颈病变进展，这在宫颈癌筛查和治疗中可能具有潜在应用价值。
