In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurolog...In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurological and oral changes. Oral features in the form of early development of Squamous cell carcinoma, usually at the lower lip and tip of the tongue may be seen. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of Ultra violet radiation, topical application of 5 fluorouracil to treat actinic keratoses, and regular evaluation by an optholmologist, dermatologist, and neurologist. Genetic counseling is an important aspect as an increased incidence of consanguineous marriages have been reported with this disorder. Here, we report an interesting case of xeroderma pigmentosum in an 18 year old male patient who presented with characterstic desquamation of gingiva, fissured tongue and geoghraphic tongue.展开更多
AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate...AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage Ⅲ (48%) and Ⅳ (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.展开更多
AIM: To clarify the effects of the xeroderma pigmentosum group D(XPD) Asp312 Asn and Lys751 Gln gene polymorphisms on the risk of esophageal cancer(EC).METHODS: A computerised literature search was conducted to identi...AIM: To clarify the effects of the xeroderma pigmentosum group D(XPD) Asp312 Asn and Lys751 Gln gene polymorphisms on the risk of esophageal cancer(EC).METHODS: A computerised literature search was conducted to identify the relevant studies from the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Odds ratios(ORs) with 95% confidence intervals(CIs) were used to assess the associations between the XPD Asp312 Asn and/or Lys751 Gln polymorphisms and EC susceptibility. Statistical analyses were performed using the software Stata 12.0. A fixed or random effects model was selected based on a heterogeneity test. Publication bias was estimated using funnel plots and Egger's linear regression method. Subgroup analyses were performed based on histological type and ethnicity.RESULTS: Thirteen case-control studies with a total of 10 comparisons for the Asp312 Asn polymorphism, including 2373 cases and 3175 controls, and 15 comparisons for the Lys751 Gln polymorphism, including 3226 cases and 5237 controls, were recruited for the meta-analysis. In terms of the XPD Asp312 Asn polymorphism, significantly increased EC risks were identified in the Asp/Asn vs Asp/Asp comparison(OR = 1.17, 95%CI: 1.02-1.33, P = 0.03) and in the dominantmodel comparison(Asn/Asn+Asp/Asn vs Asp/Asp: OR = 1.18, 95%CI: 1.04-1.34, P = 0.01). However, no significant associations were found in the Asn/Asn vs Asp/Asp comparison(OR = 1.30, 95%CI: 1.00-1.70, P = 0.05) or in the recessive-model comparison(Asn/Asn vs Asp/Asn + Asp/Asp: OR = 1.17, 95%CI: 0.91-1.50, P = 0.22). In terms of the XPD Lys751 Gln polymorphism, a significant association with EC susceptibility was found under the recessive model(Gln/Gln vs Lys/Gln+Lys/Lys: OR = 1.21, 95%CI: 1.02-1.43, P = 0.03). However, no associations were identified in the other comparisons(co-dominant model: Lys/Gln vs Lys/Lys: OR = 1.11, 95%CI: 0.94-1.31, P = 0.20; Gln/Gln vs Lys/Lys: OR = 1.31, 95%CI: 0.98-1.75, P = 0.07; dominant model: OR = 1.14, 95%CI: 0.96-1.35, P = 0.14).CONCLUSION: The results of this meta-analysis suggest that the XPD Asp312 Asn and Lys751 Gln gene polymorphisms are associated with a significantly increased risk for EC.展开更多
Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underly...Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.展开更多
着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA...着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA进行逆转录酶-聚合酶链反应(Reverse transcriptase-polymerase chain reac-tion,RT-PCR),克隆出人全长XPD cDNA,把此基因按野生型插入表达绿色荧光蛋白的pEGFP-N2质粒,构建了pEGFP-N2/XPD重组体质粒,并将其转染入整合有乙肝病毒X蛋白(Hepatitis B virus X protein,HBx)的人肝癌细胞Hep3B,分析重组细胞的XPD表达水平、HBx表达水平和细胞增殖力,为进一步研究XPD的各种生物学活性及作用机制奠定了基础。展开更多
背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相...背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相关文献,按纳入标准对文献进行筛选后提取相关信息,然后在Stata10软件中按照meta分析流程,选择合适方法计算合并的OR值及95%可信区间,并进行敏感性分析和发表偏倚的估计。结果本研究纳入国内外22篇合格文献,其中XPD312位点15篇,XPD751位点20篇。合并结果显示,携带XPD312Asn/Asn突变基因型患肺癌的危险性是野生型Asp/Asp的1.18倍(95%CI:1.03-1.34,P=0.018);XPD751位点突变基因型也与肺癌危险性升高有关(Lys/GlnOR=1.09,95%CI:1.02-1.18;Gln/GlnOR=1.24,95%CI:1.10-1.41)。亚组分析显示XPD751与肺癌的关联性仅见于欧美人群。漏斗图和Egger’s回归分析均未发现明显的偏倚。结论XPD基因312和751位点的突变与肺癌的易感性升高有关。展开更多
文摘In xeroderma pigmentosum, a rare genodermatosis, transmitted as an autosomal recessive disorder, excessive solar damage to the skin develops at an early age. The disease is characterized by cutaneous, ocular, neurological and oral changes. Oral features in the form of early development of Squamous cell carcinoma, usually at the lower lip and tip of the tongue may be seen. The disorder is associated more commonly in populations where marriage of close blood relatives is common. Treatment of the disorder includes avoidance of Ultra violet radiation, topical application of 5 fluorouracil to treat actinic keratoses, and regular evaluation by an optholmologist, dermatologist, and neurologist. Genetic counseling is an important aspect as an increased incidence of consanguineous marriages have been reported with this disorder. Here, we report an interesting case of xeroderma pigmentosum in an 18 year old male patient who presented with characterstic desquamation of gingiva, fissured tongue and geoghraphic tongue.
基金Supported by a grant from the Navarra Government 70/2004
文摘AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage Ⅲ (48%) and Ⅳ (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients.
文摘AIM: To clarify the effects of the xeroderma pigmentosum group D(XPD) Asp312 Asn and Lys751 Gln gene polymorphisms on the risk of esophageal cancer(EC).METHODS: A computerised literature search was conducted to identify the relevant studies from the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Odds ratios(ORs) with 95% confidence intervals(CIs) were used to assess the associations between the XPD Asp312 Asn and/or Lys751 Gln polymorphisms and EC susceptibility. Statistical analyses were performed using the software Stata 12.0. A fixed or random effects model was selected based on a heterogeneity test. Publication bias was estimated using funnel plots and Egger's linear regression method. Subgroup analyses were performed based on histological type and ethnicity.RESULTS: Thirteen case-control studies with a total of 10 comparisons for the Asp312 Asn polymorphism, including 2373 cases and 3175 controls, and 15 comparisons for the Lys751 Gln polymorphism, including 3226 cases and 5237 controls, were recruited for the meta-analysis. In terms of the XPD Asp312 Asn polymorphism, significantly increased EC risks were identified in the Asp/Asn vs Asp/Asp comparison(OR = 1.17, 95%CI: 1.02-1.33, P = 0.03) and in the dominantmodel comparison(Asn/Asn+Asp/Asn vs Asp/Asp: OR = 1.18, 95%CI: 1.04-1.34, P = 0.01). However, no significant associations were found in the Asn/Asn vs Asp/Asp comparison(OR = 1.30, 95%CI: 1.00-1.70, P = 0.05) or in the recessive-model comparison(Asn/Asn vs Asp/Asn + Asp/Asp: OR = 1.17, 95%CI: 0.91-1.50, P = 0.22). In terms of the XPD Lys751 Gln polymorphism, a significant association with EC susceptibility was found under the recessive model(Gln/Gln vs Lys/Gln+Lys/Lys: OR = 1.21, 95%CI: 1.02-1.43, P = 0.03). However, no associations were identified in the other comparisons(co-dominant model: Lys/Gln vs Lys/Lys: OR = 1.11, 95%CI: 0.94-1.31, P = 0.20; Gln/Gln vs Lys/Lys: OR = 1.31, 95%CI: 0.98-1.75, P = 0.07; dominant model: OR = 1.14, 95%CI: 0.96-1.35, P = 0.14).CONCLUSION: The results of this meta-analysis suggest that the XPD Asp312 Asn and Lys751 Gln gene polymorphisms are associated with a significantly increased risk for EC.
基金This work was supported by National Basic Research Program （973 Program） （Nos. 2015CB964800 and 2014CB910503）, the Strategic Priority Research Program of the Chinese Academy of Sciences （XDA01020312）, National High Technology Research and Development Program of China （2015AA020307）, National Natural Science Foundation of China （Grant Nos. 81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, and 81401159）, Beijing Natural Science Foundation （7141005 5142016）, Program of Beijing Municipal Science and Technology Commission （Z151100003915072）, Key Research Program of the Chinese Academy of Sciences （KJZDEW-TZ-L05）, the Thousand Young Talents program of China, National Laboratory of Biomacromolecules （012kf02, 2013kf05, 2013kf11, 2014kf02, 2015kfl 0）. J.C.I.B. was supported by UCAM, the G. Harold and Leila Y. Mathers Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable Trust （2012-PG-MED002） and the Moxie Foundation.
文摘Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.
文摘着色性干皮病D组蛋白(Xeroderma pigmentosum group D,XPD)是基础转录因子ⅡH(Transcript factorⅡH,TFⅡH)复合体的第二大亚基,它在转录和核苷酸剪切修复过程中都发挥着重要作用。我们利用人宫颈鳞癌上皮细胞(HeLa细胞)中提取的总RNA进行逆转录酶-聚合酶链反应(Reverse transcriptase-polymerase chain reac-tion,RT-PCR),克隆出人全长XPD cDNA,把此基因按野生型插入表达绿色荧光蛋白的pEGFP-N2质粒,构建了pEGFP-N2/XPD重组体质粒,并将其转染入整合有乙肝病毒X蛋白(Hepatitis B virus X protein,HBx)的人肝癌细胞Hep3B,分析重组细胞的XPD表达水平、HBx表达水平和细胞增殖力,为进一步研究XPD的各种生物学活性及作用机制奠定了基础。
文摘背景与目的研究表明DNA损伤修复基因-人类着色性干皮病基因D(xeroderma pigmentosum group D,XPD)多态性与肺癌的易感性有关,但各研究结论不一,本研究拟通过meta分析,定量地评价XPD312和751位点基因多态性与肺癌的关系。方法全面检索相关文献,按纳入标准对文献进行筛选后提取相关信息,然后在Stata10软件中按照meta分析流程,选择合适方法计算合并的OR值及95%可信区间,并进行敏感性分析和发表偏倚的估计。结果本研究纳入国内外22篇合格文献,其中XPD312位点15篇,XPD751位点20篇。合并结果显示,携带XPD312Asn/Asn突变基因型患肺癌的危险性是野生型Asp/Asp的1.18倍(95%CI:1.03-1.34,P=0.018);XPD751位点突变基因型也与肺癌危险性升高有关(Lys/GlnOR=1.09,95%CI:1.02-1.18;Gln/GlnOR=1.24,95%CI:1.10-1.41)。亚组分析显示XPD751与肺癌的关联性仅见于欧美人群。漏斗图和Egger’s回归分析均未发现明显的偏倚。结论XPD基因312和751位点的突变与肺癌的易感性升高有关。
