Association between DQB1 and cervical cancer in patients with human papillomavirus and family controls

Objective: The role of human leukocyte antigen (HLA) DQB1 alleles and human papillomavirus (HPV) as contributing factors to invasive cervical cancer w as investigated. To overcome problems of misleading causal inferences commo n in traditional case-control studies, a family-based test, the transmissio n/disequilibrium test, was used. Methods: Ninety-six patients with pathologically confirmed invasive cervica l cancer were ascertained. Human papillomavirus types were determined in 80 patients, of whom 81.25% were HPV-positive, and 18.75% were HPV-negative. Deoxyribonucleic acid was extracted from samples, taken from patients and t heir parents, and sequenced to determine DQB1 genotypes. Nuclear family dat a were used to test whether the DQB1 locus is associated with invasive cerv ical cancer while controlling for high-risk HPV-positive patients. The tran smission/disequilibrium test evaluates whether the frequency of transmissio n of parental marker alleles to their affected off spring deviates from the expected Mendelian frequency of 50%. Results: The HLA DQB1 locus showed evidence far allelic association with in vasive cervical cancer in high-risk HPV-positive patients (P = .006). The t ransmission/disequilibrium test showed that the DQB1*0303 allele was transm itted to high-risk HPV patients more often than expected by chance, chi(1)( 2) = 8.0, P = .005 (P = .035 when correcting for multiple tests). Tests of association were negative when applied to all 96 patients, irrespective of HPV status, No significant differences were found in the distribution of th e DQB1 alleles among HPV-positive patients compared with those who were HPV -negative, indicating that HLA alleles are not associated with susceptibili ty to HPV infection. Conclusion: These results suggest that the DQB1*0303 allele increases the r isk far invasive cervical cancer in women who are HPV-positive. (Obstet Gyn ecol 2000;95:134-40. (C) 2000 by The American College of Obstetricians and Gynecologists.).