Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CANCER ; CELL ; human ; LUNG ; MODEL ; PATHWAY ; PATHWAYS ; lung cancer ; LUNG-CANCER ; SUPPORT ; SYSTEM ; SYSTEMS ; RISK ; RISKS ; SITE ; ENZYMES ; GENE ; GENES ; GENOME ; PATIENT ; DNA ; MARKER ; BIOLOGY ; cell cycle ; CELL-CYCLE ; CYCLE ; SEQUENCE ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; HEALTH ; DNA-REPAIR ; REPAIR ; COMPONENT ; MARKERS ; DAMAGE ; HUMAN GENOME ; REGION ; REGIONS ; DNA-DAMAGE ; CANCER-PATIENTS ; CANCER PATIENTS ; CYCLE CONTROL ; MULTICENTER ; DNA repair ; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ; ONCOLOGY ; RE ; VARIANT ; CHECKPOINT ; biomarker ; INTERVAL ; ENZYME ; analysis ; DNA damage ; HAPLOTYPE ; USA ; odds ratio ; cancer research ; cell cycle checkpoints ; modeling ; cell cycle control ; block ; nonsmokers ; INTEGRITY
    Abstract: The DNA repair systems maintain the integrity of the human genome and cell cycle checkpoints are a critical component of the cellular response to DNA damage. We hypothesized that genetic variants in DNA repair and cell cycle control pathways will influence the predisposition to lung cancer, and studied 27 variants in 17 DNA repair enzymes and 10 variants in eight cell cycle control genes in 1,604 lung cancer patients and 2,053 controls. To improve the estimation of risks for specific variants, we applied a Bayesian approach in which we allowed the prior knowledge regarding the evolutionary biology and physicochemical properties of the variant to be incorporated into the hierarchical model. Based on the estimation from the hierarchical modeling, MGMT 143V or 178R, and CHEK2 157I had an odds ratio of lung cancer equal to 1.45 [95% confidence interval (95% CI), 1.05-2.00], 1.18 (95% CI, 1.01-1.40), and 1.58 (95% CI, 1.14-2.17). The association of CHEK2 1571 seems to be overestimated in the conventional analysis. Nevertheless, this association seems to be robust in the hierarchical modeling. None of the pathways seem to have a prominent effect. In general, our study supports the notion that sequence variation may explain at least some of the variation of inherited susceptibility. In particular, further investigation of OGG1, MGMT, and CHEK2 focusing on the genetic regions where the present markers are located or the haplotype blocks tightly linked with these markers might be warranted
    Type of Publication: Journal article published
    PubMed ID: 18086781
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CANCER ; BLOOD ; LUNG ; PATHWAY ; lung cancer ; LUNG-CANCER ; SUPPORT ; RISK ; GENE ; GENES ; SAMPLE ; SAMPLES ; PATIENT ; primary ; CARCINOGENESIS ; SEQUENCE ; LINKAGE ; VARIANTS ; PLASMA ; cancer risk ; LINKAGE DISEQUILIBRIUM ; Jun ; SQUAMOUS-CELL CARCINOMA ; CANCER-PATIENTS ; DIETARY ; CANCER PATIENTS ; EUROPE ; MULTICENTER ; YOUNG ; ONCOLOGY ; DIETARY FACTORS ; RE ; VARIANT ; METHYLENETETRAHYDROFOLATE REDUCTASE ; MTHFR ; LEVEL ; INTERVAL ; GENOTYPE ; HAPLOTYPE ; C677T POLYMORPHISM ; INCREASED RISK ; odds ratio ; CANCERS ; CANCER-RISK ; CHINESE POPULATION ; COMMON MUTATION ; GENOMIC DNA METHYLATION ; METHIONINE-SYNTHASE ; METHYLENE-TETRAHYDROFOLATE REDUCTASE ; METHYLENETETRAHYDROFOLATE-REDUCTASE GENE ; PLASMA HOMOCYSTEINE
    Abstract: Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 137 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/ 677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers
    Type of Publication: Journal article published
    PubMed ID: 17389614
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...