TP53, MDM2, NQO1, and susceptibility to cervical cancer.
TP53, MDM2, NQO1, and susceptibility to cervical cancer.
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DOI：
10.1158/1055-9965.epi-09-0886
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发表时间：
2010-03
期刊：
影响因子：
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通讯作者：
Rader JS
中科院分区：
文献类型：
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作者：
Hu X;Zhang Z;Ma D;Huettner PC;Massad LS;Nguyen L;Borecki I;Rader JS
宿主遗传变异改变了感染致癌性人乳头瘤病毒(HPV)的妇女患宫颈癌的风险。研究已经报道了TP53密码子72精氨酸与宫颈癌之间的关联，但结果并不一致。我们使用基于家族的关联检验，研究了这种单核苷酸多态(SNP)与宫颈癌和宫颈上皮内瘤变3级(CIN3)的相关性。我们进一步研究了调控P53稳定性的两个基因中的SNPs：MDM2(SNP309)和NQO1(SNP609，SNP465)。我们还研究了宿主基因与肿瘤HPV类型的关系。我们使用PCR-RFLP或TaqMan分析对577名患者及其亲生父母和/或兄弟姐妹进行了基因分型。用基于序列的方法对HPV进行分型。传递/不平衡检验用于检测疾病易感等位基因。Tp53密码子72的精氨酸肽在高加索家庭中过度传播(P=0.043)，这一发现在感染HPV16和/或18相关HPV的妇女亚组中的意义增强(P=0.026)。NQO1SNP609等位基因C在所有病例中均有过度传递(P=0.026)。我们未发现MDM2 SNP309或NQO1 SNP465与宫颈癌相关。我们的结果表明，TP53密码子72和NQO1 SNP609的功能多态与宫颈癌的风险相关，特别是在感染16和/或18型相关HPV的妇女中。
Host genetic variability modifies the risk of cervical cancer in women infected with oncogenic human papillomavirus (HPV). Studies have reported an association of the TP53 codon 72 arginine and cervical cancer, but the results are inconsistent. We examined the association of this single nucleotide polymorphism (SNP) in women with cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3), using family-based association test. We further explored SNPs in two genes that regulate p53 stability: MDM2 (SNP309) and NQO1 (SNP609, SNP465). We also examined the relationship between host genotype and tumor HPV type. We genotyped 577 patients and their biological parents and/or siblings, using PCR-RFLP or TaqMan assays. HPVs were typed by sequence-based methods. The transmission/disequilibrium test was used to detect disease-susceptibility alleles. The arginine peptide of TP53 codon 72 was overtransmitted in Caucasian families (P=0.043), and the significance of this finding was enhanced in a subgroup of women infected with HPV16- and/or 18-related HPVs (P=0.026). Allele C of NQO1 SNP609 was also overtransmitted in all cases (P=0.026). We found no association between MDM2 SNP309 or NQO1 SNP465 and cervical cancer. Our results indicate that functional polymorphisms in TP53 codon 72 and NQO1 SNP609 associate with the risk of cervical cancer especially in women infected with type 16- and/or 18-related HPVs.