The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polym...The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique was adopted to analyze the polymorphism of codon 133 of exon 3 in the RASSF1 gene of 100 pathologically diagnosed lung cancer patients, and 100 healthy controls. The relationship between different genotypes and the susceptibility of lung cancer was analyzed. Among 200 blood samples from Han people in Hubei Province, including 100 from lung cancer patients and 100 from healthy controls, the frequencies of Ala/Ala, Ala/Ser, Ser/Ser genotype of the RASSF1 in lung cancer patients were 83%, 16%, 1%, and those in healthy controls was 93%, 7%, 0% respectively, with the difference being statistically significant between two groups （P〈0.05）. The individuals with Ala/Ser genotype had higher risk of suffering from lung cancer, with an OR of 2.341, and 95% CI of 1.009-6.393 respectively. It was concluded that RASSF1Ala133Ser was a susceptible genetic factor of lung cancer. Ala/Ser genotype increased the risk of lung cancer.展开更多
Objective： To study the relationship between one polymorphism in the promoter of the DNA repair gene XPA and the susceptibility to lung cancer. Methods： Genotypes were determined by the PCR-restriction fragment leng...Objective： To study the relationship between one polymorphism in the promoter of the DNA repair gene XPA and the susceptibility to lung cancer. Methods： Genotypes were determined by the PCR-restriction fragment length polymorphism （PCR-RFLP） method in 310 histologically-confirmed lung cancer cases and 341 age and sex frequency-matched cancer-free controls. Results： The XPA A23G genotype frequencies were 27.1% （AA）, 42.9% （AG）, and 30.0% （GG） in case patients and21.1% （AA）, 5218% （AG）, and 26.1% （C-G） in control subjects. Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele （AG ＋ GG genotypes） had a significantly decreased risk for lung cancer （adjusted OR = 0.66; 95 % CI = 0.44- 0.98） compared with the wild-type genotype （23AA）. Stratified analysis showed that the protective effect was more evident in subjects with a family history of cancer. Conclusion： These results suggest that the XPA A23G polymorphism may have a role in lung cancer susceptibility in this study population.展开更多
Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigat...Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.展开更多
Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E...Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer.展开更多
Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal ...Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.展开更多
To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first...To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.展开更多
Recent population-based genome wide association studies have revealed potential suscepti- bility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine re- ceptor genes. The loci in...Recent population-based genome wide association studies have revealed potential suscepti- bility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine re- ceptor genes. The loci increasing lung cancer risk has been widely identified in Caucasians, but whether this association also exists in Asians and whether this association is a direct role or mediated via tobacco smoking indirectly has not been fully established. We conducted a case-control study comprising of 210 histologically confirmed lung cancer cases and 200 healthy controls to examine rsl051730 genotyping, a single nucleotide polymorphism receiving much attention recently, and its influence on lung cancer risk as well as nicotine dependence in a Chinese Han population. Our results showed that the heterozy- gous C/T genotype and minor allele T conferred a significant higher risk of lung cancer than the CC homozygotes and allele C （adjusted OR=2.25, 95% CI=1.0~4.89, P=-0.040 and OR=2.18, 95% CI=1.02~4.67, P=0.045 respectively）. However, no association between the smoking habit and the CHRNA3 rs1051730 polymorphism was observed in this study. The results suggested that the rs1051730 polymorphism may modify susceptibility to lung cancer via a smoking-independent manner among Chinese Han population. Additional studies in vitro and in vivo are warranted to further elucidate the impact ofrsl051730 on lung cancer susceptibility.展开更多
Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
Background Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer （NSCLC） patients, and genetic factors are thought to represent important determinants of drug efficacy...Background Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer （NSCLC） patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939GIn gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.Methods The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C （XPC） gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.Results The distributions of XPC Lys939GIn genotypes differed significantly between the response group （complete ＋partial responses） and the non-response group （stable ＋ progressive disease; P=0.022）. The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage Ⅲ （OR, 0.074; 95% CI,0.008-0.704; P=0.023）. The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.Conclusion Polymorphisms of the XPC gene, Lys939GIn, may be a predictive marker of treatment response for advanced NSCLC patients in stage Ⅲ.展开更多
文摘The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique was adopted to analyze the polymorphism of codon 133 of exon 3 in the RASSF1 gene of 100 pathologically diagnosed lung cancer patients, and 100 healthy controls. The relationship between different genotypes and the susceptibility of lung cancer was analyzed. Among 200 blood samples from Han people in Hubei Province, including 100 from lung cancer patients and 100 from healthy controls, the frequencies of Ala/Ala, Ala/Ser, Ser/Ser genotype of the RASSF1 in lung cancer patients were 83%, 16%, 1%, and those in healthy controls was 93%, 7%, 0% respectively, with the difference being statistically significant between two groups （P〈0.05）. The individuals with Ala/Ser genotype had higher risk of suffering from lung cancer, with an OR of 2.341, and 95% CI of 1.009-6.393 respectively. It was concluded that RASSF1Ala133Ser was a susceptible genetic factor of lung cancer. Ala/Ser genotype increased the risk of lung cancer.
文摘Objective： To study the relationship between one polymorphism in the promoter of the DNA repair gene XPA and the susceptibility to lung cancer. Methods： Genotypes were determined by the PCR-restriction fragment length polymorphism （PCR-RFLP） method in 310 histologically-confirmed lung cancer cases and 341 age and sex frequency-matched cancer-free controls. Results： The XPA A23G genotype frequencies were 27.1% （AA）, 42.9% （AG）, and 30.0% （GG） in case patients and21.1% （AA）, 5218% （AG）, and 26.1% （C-G） in control subjects. Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele （AG ＋ GG genotypes） had a significantly decreased risk for lung cancer （adjusted OR = 0.66; 95 % CI = 0.44- 0.98） compared with the wild-type genotype （23AA）. Stratified analysis showed that the protective effect was more evident in subjects with a family history of cancer. Conclusion： These results suggest that the XPA A23G polymorphism may have a role in lung cancer susceptibility in this study population.
文摘Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.
基金supported by the Chunhui Plan from Ministry of Eduction of ChinaFund for Academy Leaders and Innovative Team from Inner Mongolian Autonomous Region of china
文摘Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer.
文摘Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.
文摘To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.
基金supported by the National Natural Science Foundation of China(No.81372712)
文摘Recent population-based genome wide association studies have revealed potential suscepti- bility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine re- ceptor genes. The loci increasing lung cancer risk has been widely identified in Caucasians, but whether this association also exists in Asians and whether this association is a direct role or mediated via tobacco smoking indirectly has not been fully established. We conducted a case-control study comprising of 210 histologically confirmed lung cancer cases and 200 healthy controls to examine rsl051730 genotyping, a single nucleotide polymorphism receiving much attention recently, and its influence on lung cancer risk as well as nicotine dependence in a Chinese Han population. Our results showed that the heterozy- gous C/T genotype and minor allele T conferred a significant higher risk of lung cancer than the CC homozygotes and allele C （adjusted OR=2.25, 95% CI=1.0~4.89, P=-0.040 and OR=2.18, 95% CI=1.02~4.67, P=0.045 respectively）. However, no association between the smoking habit and the CHRNA3 rs1051730 polymorphism was observed in this study. The results suggested that the rs1051730 polymorphism may modify susceptibility to lung cancer via a smoking-independent manner among Chinese Han population. Additional studies in vitro and in vivo are warranted to further elucidate the impact ofrsl051730 on lung cancer susceptibility.
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
基金This work was supported by the grants from the Prophase Force-Study Program of the Jiangsu Province Natural Science Foundation （No. BK2005203）, the Medical Science Technology Research ＂Eleventh Five-Year＂ Program of the People＇s Liberation Army （No. 06MAlll）, and the Focal Project of Nanjing Medical Technology Development （No. ZKX05030）.
文摘Background Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer （NSCLC） patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939GIn gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.Methods The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C （XPC） gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.Results The distributions of XPC Lys939GIn genotypes differed significantly between the response group （complete ＋partial responses） and the non-response group （stable ＋ progressive disease; P=0.022）. The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage Ⅲ （OR, 0.074; 95% CI,0.008-0.704; P=0.023）. The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.Conclusion Polymorphisms of the XPC gene, Lys939GIn, may be a predictive marker of treatment response for advanced NSCLC patients in stage Ⅲ.
