Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer.
Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer.
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DOI：
10.1086/595563
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Hildesheim A
中科院分区：
文献类型：
--
作者：
Wang SS;Bratti MC;Rodríguez AC;Herrero R;Burk RD;Porras C;González P;Sherman ME;Wacholder S;Lan ZE;Schiffman M;Chanock SJ;Hildesheim A
我们检查了宿主遗传因素，以确定那些更常见于人乳头瘤病毒（HPV）感染最有可能持续并进展为宫颈上皮内瘤变3级（CIN 3）和癌症的个体。我们对来自469名CIN 3或癌症妇女、390名持续性HPV感染妇女（中位持续时间为25个月）和来自10，049名瓜纳卡斯特哥斯达黎加自然史研究妇女的452名随机对照受试者的49个候选免疫应答和DNA修复基因的92个单核苷酸多态性（SNP）进行基因分型。我们计算了与随机对照受试者相比，CIN 3或癌症和HPV持续存在的女性中SNP和单倍型相关性的比值比和95%置信区间（CI）。范可尼贫血互补组A基因（FANCA）（G501 S）中的SNP与CIN 3或癌症的风险增加相关。AG和GG基因型分别使CIN 3或癌症的风险增加1.3倍（95%CI，0.95-1.8倍）和1.7倍（95%CI，1.1-2.6倍）（P趋势= 0.008;参考，AA）。包括G501 S的FANCA单倍型也增加了CIN 3或癌症的风险，包括其他2个FANCA SNP（G809 A和T266 A）的不同单倍型也是如此。先天免疫基因IRF 3（S427 T）中的SNP与HPV持续性风险增加相关（Ptrend = .009）。我们的研究结果需要复制，但支持FANCA变异在宫颈癌易感性中的作用和IRF 3在HPV持久性中的作用。
We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95–1.8-fold) and 1.7-fold (95% CI, 1.1–2.6-fold) increased risk for CIN3 or cancer, respectively (Ptrend = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (Ptrend = .009). Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.
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影响因子：
10.4
作者：
Au, William W;Salama, Salama A;Sierra-Torres, Carlos H
通讯作者：
Sierra-Torres, Carlos H
影响因子：
51.1
作者：
Cogliano, V;Baan, R;El Ghissassi, F
通讯作者：
El Ghissassi, F
DOI：
10.1016/j.ijgo.2003.08.017
发表时间：
2004-06-01
影响因子：
3.8
作者：
Jee, SH;Won, SY;Ji, SS
通讯作者：
Ji, SS
影响因子：
3.1
作者：
Pioli, PA;Amiel, E;Guyre, PM
通讯作者：
Guyre, PM
影响因子：
4.8
作者：
O'Connell, CM;Ionova, IA;Ingalls, RR
通讯作者：
Ingalls, RR