title: HLA-DP is the cervical cancer susceptibility loci among women infected by high-risk human papillomavirus: potential implication for triage of human papillomavirus-positive women.
abstract: Given that only a small proportion of women infected by high-risk human papillomavirus (hrHPV) develop cervical cancer, it's important to identify biomarkers for distinguishing women with hrHPV positivity who might develop cervical cancer from the transient infections. In this study, we hypothesized that human leukocyte antigens (HLA) susceptibility alleles might contribute to cervical cancer risk among females infected by hrHPV, and interact with hrHPV types. A case-control study with 593 cervical cancer cases and 407 controls (all hrHPV positive) was conducted to evaluate the effect of eight HLA-related single-nucleotide polymorphisms (SNPs) and their interactions with hrHPV types on the risk of cervical cancer. Three HLA-DP SNPs (rs4282438, rs3117027, and rs3077) were found to be significantly associated with risk of cervical cancer (rs4282438: odds ratio (OR) = 0.72, 95 % confidence interval (CI) = 0.56-0.93; rs3117027: OR = 1.41, 95 % CI = 1.10-1.83; and rs3077: OR = 1.37, 95 % CI = 1.04-1.80) among women infected with hrHPV. An additive interaction between HPV16 and rs4282438 for cervical cancer risk was also found (P for interaction = 0.002). Compared with subjects carrying variant genotypes (GG/TG) and non-HPV16 infections, those carrying wild-type genotype (TT) of rs4282438 and HPV16 positive had a 5.22-fold increased risk of cervical cancer (95 % CI = 3.39-8.04). Our study supported that certain HLA-DP alleles in concert with HPV16 could have a predisposition for cervical cancer development, which may be translated for triage of hrHPV-positive women.
authors.affiliation: Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Meiqun
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Epidemiology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hang
authors.affiliation: Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Program Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
authors.forename: Lanwei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Program Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
authors.forename: Jufang
authors.initials: J
authors.lastname: Shi
authors.affiliation: Program Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, 100021, China.|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Program Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China. daimin2002@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: Program Office for Cancer Screening in Urban China, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China. lini1240@hotmail.com.
authors.forename: Ni
authors.initials: N
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D006682:HLA-DP Antigens
keywords: Cervical cancer; Genetic variants; HLA; HPV; Interaction