Christopher Amos

..We studied the influence of this p53 polymorphism on HNPCC age of onset...

..The purpose of this study was to investigate the association of the Aurora-A (T91A), and p16 (C540G and C580T) polymorphisms with age at diagnosis of pancreatic cancer...

..3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma...

..The model was subsequently used to search for and capture similarly related genes. SVMR shows promising capability in modeling and seeking gene relationships through expression data...

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..A larger sample size of the Hispanic group is needed to identify linkage regions...

..03 for imprinting, but increase in the LOD score did not meet the required threshold to reliably identify imprinting as the correct mode of inheritance in genome-wide linkage scans...

..To investigate the impact of such a transformation on real data sets, we apply variance-components and variance-regression methods to the expression data of GAW15 and compare the results before and after transformation...

..In addition, SNPs with the largest TH score on each chromosome were identified. These SNPs may be located in the regions of genes that have modest effects on rheumatoid arthritis. These regions deserve further investigation...

..However, the sibpair design is still valuable because it requires few assumptions other than acceptably high penetrance to identify genetic loci...

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..Bias can be eliminated with parental data and can be reduced when additional markers not in LD are included in the analyses...

..An alternative procedure called PennCNV uses information from both the marker intensities as well as the genotypes and therefore has increased sensitivity...

..However, a number of methodological and computational constraints have prevented the power of this simulation method from being fully explored in existing forward-time simulation methods...

..Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk...

..We also studied the effect of extended family information on risk estimation using BOADICEA...

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..The LS method was computationally rapid, over 4,000 times faster than ML estimation for bivariate data. Because ML estimation is time consuming, LS methods are suggested for initial interval mapping with multivariate data...

..Several questions could be addressed using the data, including analysis of genetic associations using single SNPs or haplotypes, as well as gene-gene and genetic analysis of SNPs for qualitative and quantitative factors...

..These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers...

..Three large consortia present comprehensive analyses that identify genetic factors influencing smoking initiation, intensity and cessation. The genetic architecture of these three phases of smoking behavior appears to be largely distinct...

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

..Time to onset of symptoms was characterised for a large collection of individuals with PJS who had been tested for STK11 mutations and genotype-phenotype correlations were evaluated...

..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...

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

..13 (1.04-4.36), 3.18 (1.37-7.39), and 10.09 (3.17-32.05), respectively. These findings suggest these polymorphisms in the cell cycle genes are promising prognostic markers for patients with pancreatic cancer...

..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...

..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...

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..These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results...

..We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to pancreatic cancer...

..The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied...

..This is the first report, to our knowledge, to show that IGF1 variant genotypes modify risk of a hereditary form of cancer...

..ATM germline mutations have been associated with breast and digestive cancers. In a smaller European study, the G-to-A polymorphism was associated with an increased risk of developing an HNPCC-related cancer within HNPCC families...

..004; HR=2.91; 95%CI, 1.49-5.67). Our findings suggest that the p21 polymorphism independently and p21 and p27 polymorphisms jointly contribute to a significantly earlier age at diagnosis of pancreatic cancer...

..Our results suggest that the I462V and Msp1 polymorphisms in CYP1A1 may be an additional susceptibility factor for disease expression in Lynch syndrome because they modify the age of colorectal cancer onset by up to 4 years...

..This is the first report to our knowledge to provide evidence that the C677T polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect...

..Similarly, pathogenic effects of >/=16% of missense mutations in the hMLH1 gene are ESE related. The colocalization of pathogenic missense mutations with ESE sites strongly suggests that their pathogenic effects are splicing related...

..Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci...

..We provide the list of the top 200 predicted PCa genes, which can be used as candidates for experimental validation. The model may be modified to predict genes for other cancer sites...

..The objectives of this study were to determine the accuracy of the BRCAPRO model among women with bilateral breast cancer and to determine whether their mutation status was dependent on their age at first diagnosis...

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..Our analysis suggests that including rare SNPs in genotyping platforms will advance identification of causal SNPs in case-control association studies, particularly as sample sizes increase...

..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...

..The169G-to-A polymorphism did not have a significant influence on risk for HNPCC. However, when we did haplotype analysis for these two polymorphisms, the 91A-169G haplotype was associated with protection from HNPCC at an earlier age...

..61, 95% CI, 1.26-2.06), light smokers (OR = 1.58, 95% CI, 1.17-2.14), and squamous cell lung carcinoma (OR = 1.79, 95% CI, 1.32-2.42). These results suggest that this p73 polymorphism may be a marker for susceptibility to lung cancer...

..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...

..Thus, the study of gene-environment and gene-gene interactions may help to identify high-risk subgroups that can be targeted for intensive smoking cessation and CRC screening interventions...

..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...

..The results suggest that suboptimal DRC is associated with increased risk of NSCLC and DRC may modulate the risk of lung cancer associated with smoking but the latter needs to be verified in larger studies...

..Haplotype analysis indicated a founder effect. We conclude that the VHL 598C>T mutation, the most common defect of congenital polycythemia yet found, was spread from a single founder 1,000 to 62,000 years ago...

..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...

..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...

..In conclusion, we found that the SNP rs398652 on 14q21 was associated with longer telomere length and a reduced risk of bladder cancer and that a portion of the effect of this SNP on bladder cancer risk was mediated by telomere length...

..AVAILABILITY: simuPOP is freely available at http://simupop.sourceforge.net, distributed under a GPL license. Cited examples are in the doc/cookbook directory of a simuPOP distribution...

..Application of our method to these families yielded significantly higher LOD scores and more-accurate recombination fractions than did analysis that did not account for individual-specific covariate information...

..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...

..These results quantitatively illustrated the spectrum of cancer risk in germline p53 mutation carriers and will provide valuable reference for the evaluation and treatment of patients with cancer...

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..Optimal strategies for a genome scan of potentially imprinted traits are discussed...

..A robust version of the LRT that adjusts for sample kurtosis showed the best power for nonnormal data. Finally, phenotype winsorization of nonnormal data reduces the bias in estimation of the major gene variance component...

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

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

..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...

..We detected disease-associated deletions within the region of human leukocyte antigen in which genomic deletions were previously discovered in rheumatoid arthritis patients...

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

..We estimated the relative oncogenicity of all missense mutations reported in the IARC p53 mutation database, and constructed a profile of oncogenicity of the missense mutations along the DNA-binding region of p53...

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

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..This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6...

..A parent-of-origin effect consistent with maternal imprinting was suggested at 99.67-111.26 Mb for body mass index, bioelectrical impedance analysis, waist circumference, and leptin concentration...

..Data on a temporal series of adolescent suicide from the US National Center for Health Statistics were analyzed using these methods...

..In addition, this SNP may serve as a prognostic marker in PDA patients who undergo the same or similar treatment as the clinical trials...

..It is not obvious whether there is a consistency between the candidate genes identified by GWAS (GWAS genes) and those identified by profiling gene expression (microarray genes)...

..Genetic susceptibility for cancer can differ substantially among families. We use trait-related covariates to identify a genetically homogeneous subset of families with the best evidence for linkage in the presence of heterogeneity...

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..We undertook this study to make the first comparison of SE allele frequencies in the healthy population with those in RA patients who do or do not harbor anti-CCP antibodies...

..This EB method for incorporating data from multiple studies into genome scan analyses seems promising...

..The results of our analysis show that the apolipoprotein E locus has no effect on interindividual variability in systolic blood pressure. We found that the longitudinal measure of heritability of systolic blood pressure is 0.32...

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..Here we examine the contribution of this susceptibility haplotype alone and in combination with CARD15 variants to CD subphenotypes and to susceptibility to ulcerative colitis (UC)...

..79; multipoint LOD of 3.72 for BMI) in region 13q32, in the European American sample. The results suggest that parent-of-origin effects, perhaps including genomic imprinting, may play a role in human obesity...

..Both random sampling and extreme sampling schemes were investigated. A multinomial logistic joint test provides the highest overall power irrespective of sample size, allele frequency, heritability, and modes of inheritance...

..Joint tests were generally more powerful for one-tailed selection under both backcross and F2 intercross situations. However, joint tests cannot be recommended for one-tailed selective genotyping if segregation distortion is suspected...

..Finally, limitations of the MOM approach are noted, and we discuss some alternative procedures that may also reduce bias...

..CONCLUSION: These results provide a rational basis for pursuing high-density linkage and association studies of RA in several regions outside of the HLA region, particularly on chromosomes 1p, 1q, and 18q...

..These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles...

..Identification ofa third predisposing gene and its underlying mutation(s) should provide insight into other genetic events that predispose to the genesis of the diverse tumor types associated with LFS and its variants...

..In this paper we use, for the first time, linkage analysis to search for alcoholism-related phenotypes in a family sample selected for smoking behavior...

..At least 7 models for estimating the probabilities of having a mutation are used widely in clinical and scientific activities; however, the merits and limitations of these models are not fully understood...

..Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q...

..This retrospective study reports the mutation frequency and spectrum of BRCA1 and BRCA2 mutations in a Hispanic population and evaluates the BRCAPRO model in Hispanics...

..We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis...

..Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer...

..Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential...

..To dissect the heterogeneity of rheumatoid arthritis (RA) through linkage analysis of quantitative traits, specifically, IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibody titers...

..Finally, we will apply the methods that we are developing as part of existing studies of obesity, cancer-predisposition and rheumatoid arthritis. ..

..The simulation approaches and analytical discoveries from our research will be widely distributed. (End of Abstract) ..

..This analysis will allow us to identify groups of African-American individuals at particularly higher risks for developing lung cancer. ..

..We are collaborating with the International Lung Cancer Consortium so that it can further validate our findings for a variety of different populations, in future initiatives. ..

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..We are collaborating with the International Lung Cancer Consortium so that it can further validate our findings for a variety of different populations, in future initiatives. ..