Bhattacharya P, Sengupta S
Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata 700 108, India.
Tissue Antigens. 2007 Oct;70(4):283-93. doi: 10.1111/j.1399-0039.2007.00894.x.
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-B07 or homozygosity of HLA-DQB103. 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-B07 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-B07 and HLA-DQB103 in our study samples. The association of p53Pro72Pro with CaCx was non-significant in the absence of HLA-B07 in HPV16/18-positive women. In this group, prevalence of p53Pro72Pro and HLA-B07 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-DQB103 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.
本研究旨在探讨印度女性中，因p53脯氨酸纯合性（Pro72Pro）导致的人乳头瘤病毒（HPV）16/18相关宫颈癌（CaCx）易感性，是否单独或与免疫遗传风险因素（如HLA-B07或HLA-DQB103纯合性）共同起介导作用。采用聚合酶链反应-限制性片段长度多态性方法，对来自以下样本的DNA进行三种遗传因素的分子检测：（i）114例CaCx样本（78例HPV16/18阳性）；（ii）195例细胞学正常的宫颈刮片（116例HPV阴性和79例HPV16/18阳性样本）。进行多因素logistic回归分析，以检验这三种因素的独立作用，并确定年龄调整优势比（OR）[95%置信区间（CI）]和P值。在这个扩大的CaCx病例样本集中，观察到HLA-B07与无症状对照者（年龄调整OR = 4.73；95% CI：1.55 - 14.45；P = 0.006）及CaCx患者（年龄调整OR = 6.14；95% CI：2.15 - 17.53；P < 0.001）的HPV16/18感染显著相关。在我们的研究样本中，HLA-B07与HLA-DQB103之间缺乏关联。在HPV16/18阳性女性中，若无HLA-B07，p53Pro72Pro与CaCx的关联不显著。在该组中，CaCx病例中p53Pro72Pro与HLA-B07共同存在的比例（7.0%）显著高于（年龄调整OR = 14.05；95% CI：1.11 - 177.30；P = 0.04）两种因素均缺乏的对照者（1.3%）。在该组中，发现HLA-DQB103纯合性（年龄调整OR = 4.75；95% CI：1.17 - 19.30；P = 0.03）或p53Pro72Pro（年龄调整OR = 5.84；95% CI：1.18 - 28.99；P = 0.03）在彼此不存在时均与CaCx显著相关，但与两种因素均缺乏者相比，二者共同存在时无显著相关性（P = 0.214）。因此，免疫遗传因素对p53Pro72Pro介导的CaCx易感性的调节可能是通过HPV16/18诱导的免疫逃逸与细胞转化之间的相互作用来介导的。
