XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis
XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis
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DOI：
10.1093/carcin/21.12.2219
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发表时间：
2000-12-01
期刊：
影响因子：
4.7
通讯作者：
Wei, QY
中科院分区：
文献类型：
--
作者：
Sturgis, EM;Zheng, R;Wei, QY
DNA修复能力是维持正常细胞功能的核心，最近已描述了几个DNA修复基因的变体，包括核苷酸切除修复基因XPD，因为我们以前报道过头颈部鳞状细胞癌(SCCHN)患者的DNA修复能力低于健康对照组，我们推测XPD的遗传多态可能与烟草相关癌症SCCHN的遗传易感性有关。为了验证这一假设，我们进行了一项以医院为基础的病例对照研究，研究对象为189名SCCHN患者和496名在年龄、性别和吸烟状况上频率匹配的无癌对照，所有受试者都是非西班牙裔白人。用限制性内切酶TftI和PstI对两个XPD基因(C22541A和A35931C)进行了分型。采用多因素Logistic回归分析计算调整后的优势比(OR)和95%可信区间(CI)。在对照组中，22541A和35931C变异等位基因频率分别为44.7%和33.8%。病例组22541A纯合子(22541AA)频率(15.9%)低于对照组(20.4%)，但与SCCHN发病风险无关(校正后OR=0.90；95%CI=0.52~1.56)，35931C纯合子(35931CC)频率(35931CC)高于对照组(11.5%)，且与SCCHN危险性增加(校正OR=1.55；95%CI=0.96~2.52)呈边缘相关，老年SCCHN发病风险较高(OR=2.22；分层分析中95%CI=1，03~4，80)、吸烟(OR=1.83；95%CI=0.79~4.27)和饮酒者(OR=2.59；95%CI=1.25~5.34)。这些结果暗示了基因与环境的相互作用，但这并未达到统计学意义。由于小组中的人数相对较少，调查结果有限，需要进一步调查加以核实。
DNA repair capacity is central in maintaining normal cellular functions, Variants of several DNA repair genes,including the nucleotide excision repair gene XPD, have been described recently, Because we previously reported that patients with squamous cell carcinoma of the head and neck (SCCHN) had lower DNA repair capacity than healthy controls, we hypothesized that inherited polymorphisms of XPD may contribute to genetic susceptibility to SCCHN, a tobacco-related cancer. To test this hypothesis, we conducted a hospital-based case-control study of 189 SCCHN patients and 496 cancer-free controls who were frequency-matched on age, gender and smoking status, All subjects were non-Hispanic whites. Two XPD polymorphisms (C22541A and A35931C) were typed using the restriction enzymes TftI and PstI, respectively. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In the controls, the frequencies of the variant 22541A and 35931C alleles were 44.7% and 33,8%, respectively. The frequency of the 22541A homozygous genotype (22541AA) was lower in cases (15.9%) than in controls (20,4%) but was not associated with risk (adjusted OR = 0.90; 95% CI = 0.52-1.56) for SCCHN, The frequency of the 35931C homozygous genotype (35931CC) was higher in cases (16.4%) than in controls (11.5%) and associated with a borderline increased risk (adjusted OR = 1.55; 95% CI = 0.96-2.52) for SCCHN, The risk was higher in older subjects (OR = 2.22; 95% CI = 1,03-4,80), current smokers (OR = 1.83; 95% CI = 0.79-4.27) and current drinkers (OR = 2.59; 95% CI = 1.25-5.34) in the stratification analysis. These results suggest a gene-environment interaction, but this did not reach statistical significance. The findings are limited due to the relatively small numbers in the subgroups and need to be verified by further investigations.