Xifeng Wu

..18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR...

..This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document...

..The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions...

..As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA...

..Uncertainty remains about urinary bladder cancer (UBC) risk for many occupations. Here, we investigate the association between occupation, industry and UBC...

..Genetic instability associated with telomere dysfunction (i.e., short telomeres) is an early event in tumorigenesis. We investigated the association between telomere length and cancer risk in four ongoing case-control studies...

..This review presents an overview of current molecular epidemiology of bladder cancer and provides a useful resource for understanding the pathogenesis of bladder cancer...

..Serum levels of insulin growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with subsequent development of several epithelial cancers in prospective studies...

..This emergent area of biomedicine could lead to substantially improved clinical outcomes for patients with adenocarcinoma or squamous cell carcinoma of the esophagus...

..Therefore, we applied a pathway-based approach to evaluate the cumulative effect of multiple polymorphisms on clinical outcome of patients with non-small cell lung cancer...

..This study is significant because it provides the first molecular epidemiologic evidence linking defects in cell cycle checkpoints and DNA damage/repair capacity to elevated lung cancer risk...

..The evidence is becoming increasingly convincing that mutagen sensitivity is a risk factor for cancer development...

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..There has been no risk assessment model for bladder cancer (BC). We developed the first model incorporating mutagen sensitivity and epidemiologic factors to predict BC risk...

..Interindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non-small cell lung cancer (NSCLC)...

..We hypothesized that latent genetic instability and proliferation potential may be associated with elevated risks of SPT and recurrence...

..This new integrative approach should facilitate identification of high-risk subgroups and has important implications in LC prevention...

..Finally, we present a number of current concerns that need to be addressed as the exciting field of molecular cancer epidemiology advances rapidly...

..The ultimate goal is the development of a comprehensive risk prediction model which integrates genetic, environment, and person risk factors to benefit disease diagnosis, prevention, and treatment...

..Understanding how specific genetic variants modify drug action pathways may provide informative blueprints for individualized chemotherapy...

..This study provides the strongest and most direct evidence that mutagen sensitivity is highly heritable, thereby validating the use of mutagen sensitivity as a cancer susceptibility factor...

..Future investigation in larger populations and functional characterizations are necessary to validate these results...

..These findings warrant further replications in different populations...

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

..Cell-cycle checkpoint controls regulate cell-cycle progression and proliferation. Alterations in cell-cycle control mechanisms are linked to tumorigenesis...

..Since chronic inflammation contributes to tumorigenesis, we hypothesized that the risk and clinical outcome of bladder cancer (BC) might be modulated by genetic variations in inflammation genes...

..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...

..Thus, among African American persons, multiple loci in the region of chromosome 15q25.1 appear to be strongly associated with lung cancer risk...

..MMP levels are elevated in bladder cancer patients correlating with more advanced stage. We tested whether polymorphisms in MMP genes modify the risk of bladder cancer invasiveness and whether smoke exposure modifies this risk...

..Polymorphisms in NER genes may influence DNA repair capacity and affect clinical outcome of bladder cancer treatment...

..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...

..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...

..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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..These findings warrant further replication in independent populations and may provide information on disease management and development of target therapies...

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..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...

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

..We hypothesized that CD1 A870 allele would be associated with higher CD1 protein expression, and increased genomic instability during EAC evolution, leading to more aggressive phenotype...

..Our results stressed the importance of taking a polygenic approach to evaluate the cumulative and interaction effects of genetic variations in the prediction of cancer risk and prognosis...

..71) increased bladder cancer risk. This is the first study to evaluate the role of germ line genetic variations in PI3K-AKT-mTOR pathway as cancer susceptibility factors that will help us identify high-risk individuals for bladder cancer...

..The contributions of these polymorphisms may jointly affect bladder cancer risk through gene-gene and gene-smoking interactions...

..The lack of any alternatives for reducing risk in these patients highlights the need for future clinical trials to prospectively validate our findings...

..With further validation, our findings may provide additional biomarkers for customized treatment of platinum-based chemotherapy for NSCLC...

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

..The identified regions and genes may become diagnostic and prognostic biomarkers as well as potential targets of therapy...

..Our data suggest that the XPA 5' non-coding region polymorphism modulates NER capacity and is associated with decreased lung cancer risk, especially in the presence of exposure to tobacco carcinogens...

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..8q24 (containing Myc) and 8p23.1 (containing CTSB) were the two most frequently amplified regions. In addition, a significant trend toward increasing amplification was associated with higher progression stage...

..These findings require further validation in independent populations...

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

..Our data also suggest that the effects of high-order interactions should be taken into consideration when evaluating OPL predisposition...

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

..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...

..Heavy carcinogen exposure may overwhelm some of the genetic effects of MMP polymorphisms. Our study confirms the importance of taking a multigenic pathway-based approach to risk assessment...

..02%; P < 0.001). These results support the hypothesis that genetic variants in BER genes contribute to bladder cancer risk through gene-gene and gene-environmental interactions...

..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...

..We also examined the functionality of the p53 variants in apoptosis and DNA repair...

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..We hypothesized that genetic polymorphisms in XP genes may predict clinical response to platinum chemotherapeutic treatment and survival in women with gynecological cancers...

..These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings...

..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...

..The protective effect of ITCs against bladder cancer was not modified by GSTM1, GSTT1 or NAT2 genotypes. This is the first epidemiological report that ITCs from cruciferous vegetable consumption protect against bladder cancer...

..9 months (log rank P = 2.28 × 10(-13)). Our results suggested that miRNA-related genetic polymorphisms may be used individually and jointly to predict the risk of SPT/recurrence of early-stage head and neck cancer patients...

..Compelling evidence has shown that miRNAs are involved in cancer initiation and progression. We hypothesized that genetic variations of the miRNA machinery genes could be associated with the risk of renal cell carcinoma...

..Future studies with larger sample sizes are warranted to further investigate whether repair of NNKOAc-induced damage, as quantified by the comet assay, could be used as a predictive marker for RCC risk...

..Recently, the authors reported that 3 single-nucleotide polymorphisms (SNPs) in 2 members of the RGS family were associated with significant reductions in the risk of cancer...

..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...

..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...

..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...

..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...

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

..4-fold risk for EC and those sensitive to both mutagens showed an 8.7-fold risk for EC. Thus, we conclude that susceptibility to DNA damage as assessed by comet assay might help identify individuals with high EC risk...

..The aim of this study was to define molecular markers of response to cetuximab therapy in a panel of urothelial carcinoma cell lines...

..In this study we modified the assay by incorporating 9 control cell lines to normalize telomere length...

..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...

..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...

..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...

..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...

..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...

..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...

..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...

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

..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...

..53 (0.34-0.82) for C-A/T-A, 0.48 (0.27-0.84) for C-A/C-C, 0.18 (0.053-0.60) for C-C/C-C and 0.57 (0.36-0.90) for C+C/C+C. These results suggest that sequence variants in the XPC gene might modulate the risk of bladder cancer...

..Cell cycle checkpoint regulation is crucial for the prevention of carcinogenesis in mammalian cells...

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..16, P=0.0009). The haplotypes "T-A" (in the order of Ala499Val-PAT-Lys939Gln) was associated with the lowest DNA damages. Our results suggested that the DRC of host cells might be modulated by specific XPC polymorphisms...

..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...

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..Deregulation of cell cycle plays an important role in tumorigenesis. Cyclin D1 gene (CCND1) is a key regulator of the G(1) phase of the cell cycle...

..However, such association was not seen in esophageal cancer patients. This study provides the first molecular epidemiologic evidence linking increased esophageal cancer risk with defects in cell-cycle checkpoints and DNA repair capacity...

..The present study provides the first evidence that miRNAs may affect esophageal cancer risk in general and that specific genetic variants in miRNA-related genes may affect esophageal cancer risk individually and jointly...

..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...

..Although microRNA (miRNA) expression signatures have been associated with the etiology and prognosis of several types of cancers, their roles in the development of esophageal adenocarcinoma have not been extensively evaluated...

..01). The present study suggests that the DRD2 alleles A1 and B1 confer greater vulnerability to tobacco use...

..These results need to be replicated in larger studies...

..These results have important implications for cancer prevention in susceptible populations...

..The ability to rapidly screen individuals for risk, using minimally invasive procedures (blood samples), has immense clinical implication, such as intensive screening and chemopreventive interventions. ..

..Such individuals may then be targeted for intervention programs such as chemoprevention or dietary modification. ..

..This multivariate prognostic study could have long-term prognostic potential by allowing greater individualization of therapy, based on the genetic makeup of the patient, thereby both increasing efficacy and reducing morbidity. ..

..The ability to identify high-risk subgroups of individuals for EAC will provide immense public health benefit for those high-risk people who may be subjected to close surveillance and chemoprevention. ..

..The ability to rapidly screen individuals for risk, using minimally invasive procedures (blood samples), has immense clinical implication, such as intensive screening and chemopreventive interventions. ..

..Our long-term plan is to refine our risk assessment in patients with BC so that we can identify high-risk subgroups of candidates for primary and secondary prevention measures. ..

..Additionally, these potential biomarkers may ultimately be used to identify individuals who should be targeted for more intense screening programs or behavior modification interventions. ..

..This multivariate prognostic study could have long-term prognostic potential by allowing greater individualization of therapy, based on the genetic makeup of the patient, thereby both increasing efficacy and reducing morbidity. ..