title: Persistent HPV16/18 infection in Indian women with the A-allele (rs6457617) of HLA-DQB1 and T-allele (rs16944) of IL-1β -511 is associated with development of cervical carcinoma.
abstract: The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β -511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies (N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38), p = 0.03] and CaCx development [OR = 2.03(1.03-5.2), p = 0.02; OR = 2.25(0.96-5.31), p = 0.04] compared with HPV-negative or HPV-cleared normal women. Considering these two loci together, it was evident that the T- and A-alleles rendered significantly increased susceptibility for development of CIN and CaCx compared with HPV-negative and HPV-cleared normal women. Moreover, the T-allele of IL-1β showed increased susceptibility for CIN [OR = 3.62(0.85-17.95), p = 0.04] and CaCx [OR = 2.39(0.91-6.37), p = 0.05] development compared with the HPV-cleared women, even in the presence of the HLA-DQB1 G-allele. Thus, our data suggest that persistent HPV16/18 infection in the cervix due to the presence of the HLA-DQB1 A-allele and chronic inflammation due to the presence of the IL-1β -511 T-allele might predispose women to CaCx development.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, India.
authors.forename: Sankhadeep
authors.initials: S
authors.lastname: Dutta
authors.forename: Chandraditya
authors.initials: C
authors.lastname: Chakraborty
authors.forename: Ranajit Kumar
authors.initials: RK
authors.lastname: Mandal
authors.forename: Partha
authors.initials: P
authors.lastname: Basu
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.forename: Chinmay Kumar
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D007194:India; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology / Q000821:virology*
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C508585:IL1B protein, human; D053583:Interleukin-1beta