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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.
AuthorsSankhadeep Dutta, Chandraditya Chakraborty, Ranajit Kumar Mandal, Partha Basu, Jaydip Biswas, Susanta Roychoudhury, Chinmay Kumar Panda
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 64 Issue 7 Pg. 843-51 (Jul 2015) ISSN: 1432-0851 [Electronic] Germany
PMID25893807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • IL1B protein, human
  • Interleukin-1beta
Topics
  • Adult
  • Aged
  • Female
  • Genetic Predisposition to Disease
  • HLA-DQ beta-Chains (genetics)
  • Human papillomavirus 16 (isolation & purification)
  • Human papillomavirus 18 (isolation & purification)
  • Humans
  • India
  • Inflammation (genetics, immunology)
  • Interleukin-1beta (genetics)
  • Middle Aged
  • Papillomavirus Infections (genetics, virology)
  • Polymorphism, Single Nucleotide
  • Uterine Cervical Neoplasms (genetics, immunology, virology)
  • Uterine Cervical Dysplasia (genetics, immunology, virology)

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