title: Predisposition to HPV16/18-related cervical cancer because of proline homozygosity at codon 72 of p53 among Indian women is influenced by HLA-B*07 and homozygosity of HLA-DQB1*03.
abstract: This study was undertaken to examine whether predisposition to human papillomavirus (HPV)16/18-related cervical cancer (CaCx) because of p53 proline homozygosity (Pro72Pro) among Indian women was mediated singly or jointly with immunogenetic risk factors such as HLA-B*07 or homozygosity of HLA-DQB1*03. Molecular detection of all three genetic factors was performed by polymerase chain reaction-restriction fragment length polymorphism using DNA from (i) 114 CaCx samples (78 HPV16/18 positive) and (ii) 195 cytologically normal cervical scrapes (116 HPV-negative and 79 HPV16/18-positive samples). Multiple logistic regression analyses were performed to examine independent effects of the three factors and to determine age-adjusted odds ratio (OR) [95% confidence interval (CI)] and P-values. HLA-B*07 was observed to be significantly associated with HPV16/18 infection in asymptomatic controls (OR(age-adjusted) = 4.73; 95% CI: 1.55-14.45; P = 0.006) and CaCx (OR(age-adjusted) = 6.14; 95% CI: 2.15-17.53; P < 0.001) in this enhanced sample set of CaCx cases. There was a lack of association between HLA-B*07 and HLA-DQB1*03 in our study samples. The association of p53Pro72Pro with CaCx was non-significant in the absence of HLA-B*07 in HPV16/18-positive women. In this group, prevalence of p53Pro72Pro and HLA-B*07 together was significantly higher (7.0%) among CaCx cases (OR(age-adjusted) = 14.05; 95% CI: 1.11-177.30; P = 0.04), compared with controls (1.3%) lacking both factors. HLA-DQB1*03 homozygosity (OR(age-adjusted) = 4.75; 95% CI: 1.17-19.30; P = 0.03) or p53Pro72Pro (OR(age-adjusted) = 5.84; 95% CI: 1.18-28.99; P = 0.03) was found to be significantly associated with CaCx, each in the absence of the other in this group but not when present jointly in contrast to those lacking both factors (P = 0.214). Thus, modulation of p53Pro72Pro-mediated susceptibility to CaCx by immunogenetic factors could possibly be mediated through cross talk between HPV16/18-induced immune evasion and cell transformation.
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata 700 108, India.
authors.forename: P
authors.initials: P
authors.lastname: Bhattacharya
authors.forename: S
authors.initials: S
authors.lastname: Sengupta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism; D015793:HLA-B7 Antigen; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006720:Homozygote; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D007194:India; D016015:Logistic Models; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D011392:Proline / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: D015235:HLA-B Antigens; C425023:HLA-B*07 antigen; D015793:HLA-B7 Antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D016159:Tumor Suppressor Protein p53; D011392:Proline