Giuliani Laura, Jaxmar Terese, Casadio Caterina, Gariglio Marisa, Manna Assunta, D'Antonio Domenico, Syrjanen Kari, Favalli Cartesio, Ciotti Marco
Laboratory of Clinical Microbiology and Virology, University Hospital Tor Vergata, Viale Oxford, 81-00133 Rome, Italy.
Lung Cancer. 2007 Sep;57(3):273-81. doi: 10.1016/j.lungcan.2007.02.019. Epub 2007 Apr 2.
As a part of our continuous search for oncogenic viruses in bronchial cancer, we extended our HPV studies to analyse also SV40, BKV, JCV and HCMV sequences in bronchial cancer and related these data with p53 codon 72 polymorphism. Fresh tumor samples from 78 patients with lung cancer were analysed for SV40, BKV, JCV, HCMV and HPV sequences by PCR. HPV genotypes were determined using reverse blot hybridization and sequencing, and all HPV-positive tumors were tested for the presence of E6/E7 transcripts by RT-PCR. All samples were analysed for p53 codon 72 polymorphism, using PCR-based RFLP method. Of the 78 cases studied, 11 (14.1%) were positive for T-Ag gene of SV40, while BKV and JCV sequences were both amplified in 1 tumor only. Altogether, 10/78 lesions were HPV-positive; six HPV16, one HPV31, two HPV6/53 and one HPV16/18. All HPV DNA-positive samples except one also expressed E6 and E7 transcripts. HCMV was amplified in 18 (23%) cases. RFLP analysis of p53 codon 72 revealed 32 homozygotes for arg/arg allele (50.8%), 26 heterozygotes for arg/pro allele (41.3%), and 5 homozygotes for pro/pro allele (7.9%). P53 codon 72 polymorphism was not significantly different between cases (n=63) and controls (n=50) (p=0.455), among virus positive and negative patients, nor was it related to HPV genotypes (p=0.384), expression of E6 (p=0.384) and E7 oncogenes (p=0.293). Of all possible combinations of virus co-detection, only SV40-HCMV association was statistically significant (OR=5.500, 95%CI 1.43-21.02; p=0.015). Taken the known mechanisms of these individual viruses, there is a chance that these viruses could affect cell cycle control and inhibit apoptosis, thus potentially causing genetic instability and promote oncogenesis.
作为我们在支气管癌中持续寻找致癌病毒工作的一部分，我们扩大了对人乳头瘤病毒（HPV）的研究范围，同时分析支气管癌中的猿猴空泡病毒40（SV40）、BK病毒（BKV）、JC病毒（JCV）和人巨细胞病毒（HCMV）序列，并将这些数据与p53基因第72位密码子的多态性相关联。通过聚合酶链反应（PCR）对78例肺癌患者的新鲜肿瘤样本进行SV40、BKV、JCV、HCMV和HPV序列分析。使用反向斑点杂交和测序确定HPV基因型，并用逆转录聚合酶链反应（RT-PCR）检测所有HPV阳性肿瘤中E6/E7转录本的存在情况。使用基于PCR的限制性片段长度多态性（RFLP）方法分析所有样本中p53基因第72位密码子的多态性。在所研究的78例病例中，11例（14.1%）的SV40 T抗原基因呈阳性，而BKV和JCV序列仅在1例肿瘤中同时扩增。总共78个病变中有10个HPV阳性；6个为HPV16型，1个为HPV31型，2个为HPV6/53型，1个为HPV16/18型。除1个样本外，所有HPV DNA阳性样本均表达E6和E7转录本。18例（23%）检测到HCMV扩增。p53基因第72位密码子的RFLP分析显示，32例为精氨酸/精氨酸等位基因纯合子（50.8%），26例为精氨酸/脯氨酸等位基因杂合子（41.3%），5例为脯氨酸/脯氨酸等位基因纯合子（7.9%）。病例组（n = 63）和对照组（n = 50）之间p53基因第72位密码子的多态性无显著差异（p = 0.455），病毒阳性和阴性患者之间也无差异，且与HPV基因型（p = 0.384）、E6表达（p = 0.384）和E7癌基因（p = 0.293）均无关联。在所有可能的病毒联合检测组合中，只有SV40与HCMV的关联具有统计学意义（比值比[OR]=5.500，95%置信区间[CI]为1.43 -
