title: Cervical cancer in Indian women reveals contrasting association among common sub-family of HLA class I alleles.
abstract: We studied the relationship between human leukocyte antigen (HLA) class I alleles and cervical cancer among Indian women. Seventy-five cervical cancer cases were compared with 175 noncancer controls. Cervical biopsy tissue specimen from cancer cases and cervical swab specimen from controls were collected for HPV detection and typing. Blood was taken for HLA typing by PCR-SSOP method. The impact of HLA class I alleles on cervical cancer risk was evaluated using StatCalc program (Epi Info version 6.0.4. CDC Atlanta, GA, USA), and confirmed with Bonferroni correction. Results revealed HLA-B*37, HLA-B*58 were associated significantly with increased risk while HLA-B*40 with decreased risk for cervical cancer. At high-resolution analysis after Bonferroni correction, HLA-B*37:01 allele was associated with increased risk, whereas HLA-B*40:06 was with decreased risk for cervical cancer. HLA-B*37:01 and HLA-B*40:06 belong to the same superfamily of HLA-B44. In silico analysis revealed different binding affinities of HLA-B*37:01 and HLA-B*40:06 for the epitopes predicted for E6 and L1 proteins of HPV16. The higher binding affinity of epitopes to B*40:06, as revealed by docking studies, supports the hypothesis that this allele is able to present the antigenic peptides more efficiently than B*37:01 and thereby can protect the carriers from the risk of cervical cancer. Thus, there is a clear indication that HLA plays an important role in the development of cervical cancer in HPV-infected women. Identification of these factors in high-risk HPV-infected women may help in reducing the cervical cancer burden in India.
authors.affiliation: National Institute for Research in Reproductive Health, Mumbai, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gokhale
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mania-Pramanik
authors.forename: Archana
authors.initials: A
authors.lastname: Sonawani
authors.forename: Susan
authors.initials: S
authors.lastname: Idicula-Thomas
authors.forename: Shilpa
authors.initials: S
authors.lastname: Kerkar
authors.forename: Hemant
authors.initials: H
authors.lastname: Tongaonkar
authors.forename: Hemangi
authors.initials: H
authors.lastname: Chaudhari
authors.forename: Himangi
authors.initials: H
authors.lastname: Warke
authors.forename: Vinita
authors.initials: V
authors.lastname: Salvi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics; D016022:Case-Control Studies; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007194:India; D008875:Middle Aged; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology; D044465:White People / Q000235:genetics*
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I