Susan L Slager

..These results were further supported by a recent meta-analysis of our GWAS with two other GWAS of CLL, supporting the IRF8 gene as a strong candidate for CLL risk...

..These variants also showed a trend towards association with some of the other NHL subtypes. Our results validate the prior work and support specific genetic pathways for risk among NHL subtypes...

..This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development...

..The challenge of future studies of this type will be overcoming study design issues, including definition of CLL, sample size limitations and multiple testing issues...

..For each approach, multipoint linkage analysis was performed using the residuals and the SOLAR computer program. Our results show little difference between the methods based on the LOD scores...

..Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies...

..One measure of disease severity is the Gleason score. Using the Gleason score as a measure of tumor aggressiveness, several independent genome scans have reported evidence of linkage. As of yet, however, no genes have been implicated...

..The formulas make no assumptions about Hardy-Weinberg equilibrium, but do assume random ascertainment of cases and controls, all of whom are independent of one another. We demonstrate the accuracy of the formulas by simulations...

..An application of our method, to family data from a prostate cancer study, is presented to illustrate the method's utility...

..In conclusion, stoppage, a realistic scenario for some complex diseases, can represent a serious and potentially intractable problem for segregation analysis...

..A recent genome-wide association study of CLL identified seven genetic variants that increased the risk of CLL within a European population...

..The LOD score provides the lowest power in the presence of LD for the range of GRR considered here...

..We also find GEE to fail at least 5% of the time for each simulation configuration; at times, the failure rate reaches above 80%. In summary, our robust method may be the only current regression analysis method available for MCC data...

..These data provide minimal support for major effects from the examined micronutrients on overall or molecularly defined CRC risks in the IWHS cohort...

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..Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive...

..015; OR = 0.68; 95% 0.56-0.84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk...

..Using clinically relevant criteria to distinguish between monoclonal B-cell lymphocytosis (MBL) and CLL could minimize patient distress caused by labeling asymptomatic people at low risk for adverse clinical consequences as having CLL...

..99, P = 0.009, overall survival-HR 1.93, P = 0.021). Elevated pretreatment serum IP-10 levels are therefore associated with an increased likelihood of disease relapse and an inferior survival in patients with DLBCL...

..These findings provide little additional evidence for a susceptibility locus for panic disorder either within the CREM gene or in a nearby region of chromosome 10p11 in our sample...

..The in vitro observation that statins reduce rituximab efficacy does not appear to have clinical significance in CLL care...

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..To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL)...

..In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS)...

..Non-Hodgkin lymphoma (NHL) is a malignancy of lymphocytes, and there is growing evidence for a role of germline genetic variation in immune genes in NHL etiology...

..1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis...

..05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women...

..47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing...

..The strengths and weaknesses of microsatellite versus SNP markers are illustrated by the results of our genome linkage scans...

..We propose that more sensitive and accurate diagnostic methods for CLL have decreased the perceived prevalence of AID cytopenia and that improvements in management could have increased the survival of these patients...

..The FLC assay is a simple, widely available clinical test with similar prognostic utility as routinely used prognostic biomarkers for CLL. Among persons with FLC abnormalities, the type of abnormality affects prognostic significance...

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..Abnormal immune function is a key factor in predisposition to non-Hodgkin lymphoma (NHL). We evaluated the association of 30 cytokines individually and as a profile with diffuse large B-cell (DLBCL) and follicular (FL) lymphomas...

..In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, has recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL...

..No patient required blood cell transfusions after cycle 1 of therapy. We conclude that R-CVP is effective and tolerable therapy for autoimmune cytopenia complicating progressive CLL, but the duration of response is suboptimal...

..A study was undertaken to analyze the survival of chronic lymphocytic leukemia (CLL) patients relative to age-matched individuals in the general population and determine the age-stratified utility of prognostic testing...

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..Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers, although there are no data for NHL...

..The effectiveness with which physicians help patients adjust to the physical, intellectual, and emotional challenges of CLL appears to impact patient QOL...

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..Conclusions: Using our suggested workflow both algorithms performed similarly; however, fewer samples were removed and CRLMM took half the time to run our 854 study samples (4.2 h) compared to Birdseed (8.4 h)...

..3 ng/mL in those with the high-risk alleles (P = 0.02). Taken together, our data suggest that genetic variation in the TNFSF13B gene is significantly associated with NHL risk and elevated serum BAFF levels...

..e. CD5+B-CLPD) are poorly defined...

..Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer...

..019). The clinical implications of 13q- in CLL appear more complex than originally appreciated...

..Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the disease course of these cancers once they occur...

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..In summary, we conclude, as have other published reports, that normalization methods play an important role in the linkage results, and that some significant linkage signals might be due to a specific normalization method...

..Our results do not support MSR1 as a risk factor for prostate cancer...

..Because colorectal carcinogenesis is a heterogeneous process, we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer...

..Overall, the FACT-G was a valid measure for monitoring QoL over time in patients with NHL. However, sensitivity analyses based on subscale scoring that excludes potentially problematic items may be warranted...

..Finally, these risk alleles do not seem to be associated with survival...

..In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status...

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..The natural history of clinically identified MBL is unclear. The goal of this study was to explore the outcome of patients with MBL relative to that of individuals with Rai stage 0 chronic lymphocytic leukemia (CLL)...

..e., whether a SNP or haplotype is responsible); unfortunately, this is often unknown at the time of SNP selection. Additional evaluations using empirical and simulated data are needed...

..82; P=.03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC...

..The clinical impact of statin use on the outcome of lymphoma patients treated with a rituximab-containing regimen is unknown...

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..At present it is best to indicate to concerned CLL patients that their relatives are at relatively low risk of developing CLL or other LPDs...

..Revisions of the National Cancer Institute Working Group 96 criteria should consider the aetiology of cytopenia in staging CLL patients...

..This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis...

..Physicians should strictly adhere to established criteria to initiate treatment for CLL patients who are not participating in clinical trials...

..CONCLUSIONS: Our findings provide strong evidence for a susceptibility locus for panic disorder either within the COMT gene or in a nearby region of chromosome 22...

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..We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths...

..We conclude that variation in the genes encoding p50 and c-Rel may play a role in NF-kappaB-related transcription of FAS, IRF1, and CD40...

..The effects of CLL on QOL appear to differ from that of other malignancies with a more marked impact on emotional QOL. Research identifying efficacious psycho-oncologic support interventions for patients with CLL is needed...

..Together, these data identify a novel lymphoma-associated mutation in human BAFF-R that results in NF-κB activation and reveals TRAF6 as a necessary component of normal BAFF-R signaling...

..In addition, we report suggestive evidence for linkage on chromosome 4 (D4S403, P=.00012). The results of previous findings, together with our results, provide strong evidence that chromosome 19 harbors a gene for tumor aggressiveness...

..Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC...

..Thus, the TDT may not be an optimal test in the context of genomic screens under more biologically realistic assumptions...

..We saw no increased risk in relatives of HC-MGUS probands. We conclude that the prevalence of LC-MGUS is significantly higher among 1° relatives of MM probands compared to the reference population...

..Intriguingly, we observe that a number of the less frequent alleles of many of the SNP markers were associated with the nonresponse and nonspecific phenotypes...

..These findings indicate that the bone morphogenetic protein-signaling pathway is defective in patients with primary pulmonary hypertension and may implicate the pathway in the nonfamilial forms of the disease...

..These results suggest that, despite the involvement of the 2q33-q36 chromosomal region in another organ-specific autoimmune disease, it is unlikely that this region harbors a RA susceptibility locus...

..The results reported here provide little support for the role of these polymorphisms in panic disorder...

..We sought to replicate our previous findings that SLC6A4 is associated with response to a selective serotonin reuptake inhibitor (SSRI) in a large case-control study...

..0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology...

..002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci...

..We sought to determine whether clinical response or tolerance to the Selective Serotonin Reuptake Inhibitor (SSRI) citalopram is associated with genetic polymorphisms in potentially relevant pharmacokinetic enzymes...

..We sought to test further the hypothesis that SLC6A4 is associated with SSRI response by resequencing this gene in subjects with major depression...

..This study assessed the associations between pacifier use, digit sucking, childcare attendance, and breastfeeding cessation among 1387 infants in the Iowa Fluoride Study...

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..We expect to identify at least one significant chromosomal region through the linkage analysis conducted in Aim 3. We will then fine map these regions by genotyping additional markers within the regions. ..

..Identifying and understanding these genes will inform our limited biology of CLL, as well as improve risk prediction and stratification, and may enable identification of patients who will benefit from early prevention strategies. ..