Margaret Spitz

..Coupling epidemiologic data with an in vitro screen of commonly used therapeutic agents may identify novel applications for further clinical testing...

..In this analysis we examined the relationship between susceptibility to smoking and well-known risk factors associated with smoking initiation among a cohort of 11 to 13 year old Mexican origin youth residing in Houston, Texas...

..It has been previously reported that smokers with low hOGG1 activity had significantly higher risk of developing lung cancer as compared to smokers with high hOGG1 activity...

..Weight gain in early adulthood and smoking thus appear to be important predictors of virulent prostate cancer. Our data also suggest that prior screening is associated with diagnosis of lower-volume and lower-score disease...

..We will provide examples of how changes in the function of a single gene can contribute to susceptibility to carcinogenic exposure, predisposition to cancer development, patient prognosis, and prediction of outcome...

..Finally, from these data, we cannot exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels...

..Reliable risk prediction tools for estimating individual probability of lung cancer have important public health implications. We constructed and validated a comprehensive clinical tool for lung cancer risk prediction by smoking status...

..Thus, we conclude that the variants are implicated both in smoking behavior and more directly in lung cancer risk...

..Addition of biomarker assays improved the sensitivity of the expanded models...

..Some of the inconsistencies reported in the role of GST genotypes in lung cancer risk could be due to unexpected confounding from dietary factors...

..These results suggest that the two XPD polymorphisms have a modulating effect on DRC, especially in the cases...

..However, there will always be the need for impeccably designed and well-powered epidemiologic studies with rigorous quality control of data, specimen acquisition and statistical analysis...

..Data were available for 303 patients who were enrolled in a placebo-controlled chemoprevention trial of low-dose 13-cis-retinoic acid to reduce the occurrence of SPTs...

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..We concluded that these NER polymorphisms may modulate DRC and may be useful biomarkers for identifying individuals at risk of developing cancer...

..Polymorphisms in NER genes may cause variations in DNA repair capacity and increase susceptibility to both premalignant lesions and cancer...

..001). These data suggest that the VDR f and t alleles and their genotypes may protect against SCCHN. However, further studies are warranted to confirm these findings...

..We conclude that these polymorphic p16 genotypes or haplotypes may not play a major role in the etiology of SCCHN, if any. However, our limited sample size and power call for larger studies for additional verification of our findings...

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..CONCLUSIONS: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM...

..These findings suggest that these potentially functional SNPs may collectively contribute to susceptibility to SCCHN. These findings need to be validated in larger, independent studies...

..As risk assessment for cancer risk is moving toward a multigenic pathway-based approach, future genotype-phenotype correlation studies should also investigate the combined effects of multiple genetic variants...

..In conclusion, our data provide evidence that support the association between the MTR A2756G and MTRR G66A polymorphisms and SCCHN risk and that these two polymorphisms may have a joint effect on risk of SCCHN...

..The objective was to assess whether two polymorphisms in the nucleotide excision repair gene XPD (ERCC2) are markers of SCCHN risk...

..We hypothesized that this p27 T109G polymorphism is associated with squamous cell carcinoma of the head and neck (SCCHN) risk...

..Renal cell carcinoma accounts for 85% of all renal cancers. No studies have investigated the association between mtDNA content and the risk of renal cell carcinoma...

..Smoking and XRT combined enhanced the effect of either alone, with marked increased risks of lung carcinoma after XRT for breast carcinoma...

..42 [2.63-15.69], 2.86 [1.39-5.90], 3.69 [1.73-7.90], and 2.46 [1.19-5.09], respectively). CONCLUSIONS: Reduced expression of ERCC1, XPB/ERCC3, XPG/ERCC5, and CSB/ERCC6 is associated with a more than two-fold increased risk of SCCHN...

..Future studies should incorporate detailed data on alcohol consumption, dietary folate intake and related serologic measurements...

..19, 0.66) protective genotypes as compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of respiratory disease in lung cancer is unclear. Further study may yield new insights for identification of susceptible subgroups...

..64-1.36 for AA versus CC) neither in all cases nor in different histopathologic types. The results of this large case-control study suggest that this LIG1 polymorphism may not play an important role in susceptibility to lung cancer...

..001). Our results suggest that the presence of these two p21 polymorphisms may be a marker of genetic susceptibility to SCCHN...

..53; 95% CI 0.21-1.33). These data demonstrate that the GSTP1 exon 6 polymorphism, but not the exon 5 polymorphism, is associated with lung cancer risk that is especially evident in men, younger individuals, and ever smokers...

..This report provides further support for the hypothesis that a single nucleotide polymorphism in the MPO gene is a protective factor in lung cancer carcinogenesis...

..Given the limitations with case-control studies, these findings need to be confirmed in further investigations...

..To test the hypothesis that common sequence variants of cell cycle control genes may affect lung cancer predisposition...

..78; 95% CI=1.06-3.00), but not in never smokers (OR=1.19; 95% CI=0.65-2.20). These results suggest that the NQO1 genetic polymorphism modulates bladder cancer risk, especially in men and ever smokers...

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..These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events...

..The biological role of HRT in lung cancer remains understudied, and only extensive research can yield new insights into the mechanisms underlying a protective effect of HRT for lung cancer...

..To our knowledge, this is the largest study conducted evaluating the functional relevance of these polymorphisms...

..We explored if polymorphisms in candidate cytokine genes could explain variability in self-reported pain in lung cancer patients of all stages...

..Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms...

..81, 95% CI = 1.04 to 3.14) but not after BPDE treatment (OR = 1.69, 95% CI = 0.98 to 2.93). CONCLUSION: Latent genetic instability as measured by the comet assay is associated with an increased estimated relative risk of bladder cancer...

..18; 95% CI, 1.13-4.22). This study provides evidence of a preventive role for carotenoids in bladder cancer, and these data may have important implications for cancer prevention, especially for individuals susceptible to DNA damage...

..As observed in tobacco-associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos-associated carcinogenesis...

..CONCLUSIONS: The results from this study demonstrated that 3p21.3 may be a specific molecular target of tobacco carcinogens and that BPDE sensitivity at this locus may reflect an individual's genetic susceptibility to HNSCC...

..These data suggest that alteration in the apoptotic pathway may be a risk factor for lung cancer and this risk may be modulated by the Fas -A670G polymorphism. Larger prospective studies are needed to verify these findings...

..Using such a molecular evolutionary approach may hold great promise for prioritizing SNPs to be genotyped in future molecular epidemiological studies...

..70; 95% CI, 1.19-2.43), women (1.61; 1.09-2.37), current smokers (1.77; 1.25-2.51) and patients with oral cancer (1.54; 1.15-2.07). Our results suggest that this p73 polymorphism may be a risk marker for genetic susceptibility to SCCHN...

..26; 95% CI, 1.02-4.99). These findings suggest that the variant XRCC3 18067TT genotype may not play a major role in the etiology of SCCHN but may contribute to a subset of SCCHN. Larger studies are needed to verify these findings...

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..74, 95% CI: 1.08-2.29) and heavy smokers (OR=1.45, 95% CI: 1.05-2.00). Our results support the hypothesis that a genetic polymorphism in the SULT1A1 gene may be associated with increased lung cancer risk...

..Arg/Arg; P=0.066 for Pro/Pro and Arg/Pro combined vs. Arg/Arg). While the results suggest that the P53 codon 72 polymorphism may contribute to oral cancer susceptibility, larger studies are needed to confirm these findings...

..In the current case-control study, the authors investigated the association between MBD2 expression and bladder carcinoma risk...

..Our results suggest that tailoring primary prevention programs by a youth's susceptibility status may increase the efficacy of prevention efforts among Mexican origin youth...

..However, it has not been established whether the association between genetic variants and lung cancer risk is a direct one or one mediated by nicotine dependence...

..In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well...

..This reports also demonstrated the chemopreventive effects of green tea extract on BPDE-induced DNA damage. These observations provide further support for the application of the comet assay in molecular epidemiologic studies...

..We hypothesized that polymorphisms of the thymidylate synthase (TYMS) gene, which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk...

..Furthermore, HPV-16 infection does not appear to be more common in never-smokers than ever-smokers with SCCHN...

..67 [0.84, 3.32]) and lung cancer (OR = 2.49 [0.81, 7.67]). Our findings suggest that chromosome 9 aberrations in PBLs might be considered a marker of lung cancer predisposition and may be associated with familial aggregation of cancer...

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..The finding that the functional RAD51 172G>T SNP, particularly in the presence of the P53 Arg72Arg genotype, may be a marker of susceptibility to SCCHN needs to be validated by larger studies of different ethnic populations...

..Our findings suggest that non-synonymous SNPs in MGMT are associated with modestly increased risk of lung cancer in Caucasians and need to be further investigated...

..We conclude that variability in DRC is a risk factor for lung cancer and our results provide proof of principle for a new assay that can assess DRC for NNK-induced DNA damage...

..These results suggest that SHMT1 variants may play a role in the etiology of lung cancer, and our findings need to be verified in larger prospective studies...

..Our assay provides a new tool to specifically quantify DNA repair capacity in bladder cancer studies and, therefore, contributes to our goal of further elucidating bladder carcinogenesis...

..Furthermore, this study underscores the importance of incorporating germ-line genetic variation data with clinical and risk factor data in constructing prediction models for clinical outcomes...

..These features make the LUC-based HCR assay suitable for molecular epidemiological studies...

..Our findings provide the first evidence linking the mutagen-induced telomerase activity in peripheral blood lymphocytes to the risk of bladder cancer, which warrants further investigation in large-sized studies and other cancer types...

..Our data suggest that there is a possible protective role of dietary folate in lung carcinogenesis, a finding which may have implications in public health and cancer prevention...

..45% of controls) exhibited a reduced lung cancer risk (OR=0.78, 95% CI=0.63-0.97). This is the first epidemiological study to report significant associations between STK15 polymorphisms and lung cancer risk...

..The authors sought to define clinicopathologic features associated with mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC)...

..Analogous results were obtained for former and never smokers. CONCLUSIONS: Genetic susceptibility constitutes an important factor in the selection of a high-risk group for early lung cancer detection...

..Understanding the factors that contribute to physical activity (PA) in Mexican-origin adolescents is essential to the design of effective efforts to enhance PA participation in this population...

..Simulation results show that tobacco control policies have achieved 35% of the reduction in lung cancer mortality that would have resulted from cessation of all smoking in 1965...

..The purpose of the current study was to determine whether smoking during chemotherapy or chemoradiation therapy for nonsmall cell lung cancer (NSCLC) affects treatment outcome...

..1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer...

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..The myeloperoxidase G-463A polymorphism was significantly protective in "ever" smokers but not in "never" smokers. Myeloperoxidase is a key enzyme in tobacco-induced carcinogenesis...

..67, CI = 2.21 to 14.60, both of which were located in the 15q24-25.1 locus, than among control subjects. Thus, further research to elucidate causal variants in the 15q24-25.1 locus that are associated with lung cancer is warranted...

..The team of investigators is multi-disciplinary and will be able to respond in a timely and flexible manner to network directives, and to enhance and augment the network's research capabilities. ..

..This research is also applicable to other sites since tobacco-specific nitrosamines are causative agents in esophagus, pancreas and oral cavity cancers, and are the most prevalent carcinogen in snuff products. ..

..These findings will enable us to develop culturally and age-appropriate school- and community-based smoking cessation interventions. ..

..Finally we will incorporate these findings into an extended risk prediction model for lung cancer. ..

..The use of genetic markers of risk enhances the power of this multidisciplinary epidemiologic research project...

..The public health potential of a useful risk prediction modes for lung cancer is substantial. ..