Host genetic polymorphism analysis in cervical cancer.
Host genetic polymorphism analysis in cervical cancer.
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DOI：
10.1093/clinchem/48.8.1218
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发表时间：
2002-08
影响因子：
9.3
通讯作者：
Eric S Calhoun;Renee M McGovern;Carol A Janney;J. Cerhan;Stephen J Iturria;David I. Smith;B. Gostout;D. Persing
中科院分区：
文献类型：
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作者：
Eric S Calhoun;Renee M McGovern;Carol A Janney;J. Cerhan;Stephen J Iturria;David I. Smith;B. Gostout;D. Persing
背景技术宫颈癌的自然史包括潜伏期，该潜伏期可能涉及人乳头瘤病毒感染的长期免疫耐受。确定病毒持久性的宿主决定因素可能有助于更好地了解耐受机制，并可能导致开发出能够对高危个体进行更有针对性的随访的测试。方法将来自 127 名宫颈癌患者的 4 个候选基因的 12 个多态性位点的基因型频率与由 108 名女性献血者组成的对照组进行比较。通过 PCR 扩增和分离的基因组 DNA 的直接测序确定基因型。结果 肿瘤坏死因子-α (TNFα) -238 多态性在宫颈癌患者中明显不足[杂合子 (HET)，比值比 (OR) = 0.33； 95% 置信区间 (CI)，0.11-0.96]，TNFα -376 多态性也是如此（P = 0.02；病例中任何变异基因型为 0%，对照为 4.7%）。 NRAMP1 3'非翻译区STP+86多态性似乎也与宫颈癌呈负相关，但这一结果并未达到统计学显着性（HET，OR = 0.57；95% CI，0.32-1.02）。 p53 密码子 72 精氨酸等位基因显示与宫颈癌存在提示性负相关（HET，OR = 0.49；95% CI，0.14-1.63；纯合子，OR = 0.35；95% CI，0.11-1.17）。测试的其余等位基因显示与宫颈癌没有关联。结论 我们确定了可能与宫颈癌风险相关的宿主遗传多态性，其中一些与细胞免疫反应或抗原加工的潜在功能影响有关。我们未能证实早期关于携带 p53 P72R 等位基因的女性宫颈癌易感性增加的报道。尽管我们的研究结果支持一般假设，即除 II 类 MHC 之外的宿主免疫遗传决定因素可能在宫颈癌的发展中很重要，但需要对包含所涉及的 TNFα 单核苷酸多态性的 HLA 基因簇进行进一步分析，以确定它们的关联是否是连锁独立的。
BACKGROUND The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. METHODS Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. RESULTS The tumor necrosis factor-alpha (TNFalpha) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFalpha -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3' untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. CONCLUSIONS We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFalpha single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.