bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1840: P53 codon 72 SNP (R72P) and prostate cancer risk
Authors: Rogler Anja , Rogenhofer Michael , Tannapfel Andrea , Borchardt Albert , Lunz Jens-Claudio , Hofstädter Ferdinand , Hartmann Arndt , Stoehr Robert 
Published: February 2011

Abstract
Aims: The tumor suppressor p53 plays a major role in stress responses of the cell and modulates cell cycle arrest and apoptosis. The p53 R72P SNP (G/C) was found to be associated with increased risk of various malignancies. However, for prostate cancer only limited data are available, especially in Caucasian population. We therefore analysed the distribution of the R72P SNP in male Caucasian prostate cancer patients and a healthy control group.
Methods: Peripheral blood or normal prostate tissue from formalin-fixed, paraffin-embedded tissue sections were used for DNA isolation. Allelic variants of p53 Codon 72 SNP were determined using RFLP analysis. Overall, 194 male patients without any malignancy (mean age 67,3 ±10,6, range 34-88) and 118 male consecutive prostate cancer patients (mean age 64,2 ±6,0, range 46-74) were investigated.
Results: The distribution of the p53 R72P SNP did not differ significantly between prostate cancer patients and the control group (Cases GG 55.1%, GC 37.3%, CC 7.6%; Controls GG 53.6%, GC 40.7%, CC 5.7%). There was also no association between the allelic variants and Gleason score (Gleason sum &lt; 7 GG 61.2%, GC 32.7%, CC 6.1%; Gleason sum ≥ 7 GG 53.3%, GC 38.3%, CC 8.3%). Significant difference in the distribution of the R72P SNP regarding onset of the disease was found (p=0,035), showing increased frequency of the proline variant in younger patients (Age ≤ 60 GG 37%, GC 3.7%, CC 59.3%; Age &gt; 60 GG 60.7%, GC 8.3%, CC 31%). Regarding recurrence, a trend towards increase of the G-allele was found in patients with early recurrence (Cases with recurrence GG 81.3%, GC + CC 18.7%, Cases with recurrence GG 50%, GC + CC 50%, p=0.039).
Conclusions: The overall risk of prostate cancer is not associated with R72P SNP. However, disease onset might be modulated by the p53 variant allele suggesting an important role of apoptosis regulation in prostate carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1840.
Abstract 1842: Familial demonstration of the involvement of E-cadherine germ-line mutation in inherited invasive lobular breast carcinomas
Authors: Zeming Xie , Zeming Xie , Uhrhammer Nancy , Bignon Yves Jean 
Published: February 2011

Abstract
Introduction
Germline mutations of the CDH1 (epithelial cadherin, OMIM 192090) gene have been extensively studied in hereditary diffuse gastric cancer (HDGC) families. Carriers of CDH1 germline mutations have a cumulative gastric cancer risk of 40-67% for men and 63-83% for women. Putative associated risk of lobular breast cancer(LBC) has also been documented in some HDGC families. Here we report a 86 members family, with a deleterious CDH1 germline mutation identified in 3 LBC affected members on 2 successive generations, 2 of them being bilateral LBC cases. It is noteworthy that no DGC was observed in this family.
Subjects and Methods
The family is of Caucasian origin, with 5 women affected by breast cancers. The proband is a female diagnosed with ILBC at the age of 60, her daughter was diagnosed with bilateral ILBC at the age of 42, one of her sisters died of breast cancer diagnosed at the age of 53, histological type was unknown. Two of her cousins were also diagnosed with breast cancer at the age of 63 and 54 respectively (one is a bilateral ILBC, another unknown). There is no confirmed diffused gastric cancer diagnosis in the history of this family. The affected members, their offspring, and siblings were recruited for genetic consultation. Two independent blood samples were tested after signing informed consent for each family member. Complete screening of CDH1, BRCA1 and BRCA2 genes was performed on 7 cases by sequencing exons and intron-exon boundaries.
Results
No BRCA1 and BRCA2 mutations were found in the family. A CDH1 Q95X germ-line mutation was found in all the 3 living women with invasive lobular breast cancers (2 of them developed bilateral ILBCs) and a 71-year-old healthy male member (one of the brothers of the proband). The mutation is also present in an obligatory carrier woman who developed a pancreatic cancer at the age of 56. Gastrointestinal endoscopy was recommended for indicative living individuals during genetic consultations, when they harbored the CDH1 mutations. No suspected gastric lesion was found.
Conclusion
Our report demonstrates the first clear example of the involvement of a deleterious E-cadherine germ-line mutation in inherited invasive lobular breast carcinoma. Screening for CDH1 mutation should be considered in families with multiple ILBC cases, even in the absence of DGC cases; ILBC risk should be considered for female carriers during consultations; prophylactic gastrectomy may not be regularly recommended in CDH1 mutations carriers without family histories of DGC.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1842.
Abstract 1846: Identification of a germline mutation in PMS2, a DNA mismatch repair gene, in a large consanguineous family with a history of Pediatric GBMs
Authors: Killela Patrick J. , Rasheed Ahmed B. , Yan Hai 
Published: February 2011

Abstract
Glioblastoma multiforme (GBM) is the most frequent and malignant human brain tumor. It is widely accepted that human cancer is a genetic disease caused by sequential accumulation of cancer gene mutations. Specifically, the gene or genes which initiate GBM formation has yet to be identified. Through collaboration with the Pakistani National Genetic Institute we have identified a consanguineous family presenting with a history of Pediatric GBMs to conduct comprehensive genomic analysis in hopes of identifying this “gatekeeper” gene. In this pedigree four children are deceased from GBM while an additional five infants have died within 4 days of birth without diagnosis. GBM has been the only diagnosed cancer in this family, indicating the existence of a GBM-specific germline mutation as a causative agent for the GBM clinical phenotype. Comprehensive genomic analysis has been conducted to elucidate a genetic aberration which is inherited and can be attributed to the GBM presenting clinical phenotype. We have collected blood and tumor DNAs for this family and performed sequencing on numerous genes including TP53, APC, IDH1, IDH2, PMS2, MLH1, MSH2, and, MSH6. Sequencing has successfully identified a germline frame shift mutation (p.Y181X) in PMS2. All affected patients have a homozygous mutation while their parents are both heterozygous carriers, suggesting the homozygous inheritance of this mutation is a causative agent for the GBM clinical phenotype. Our study suggests that the PMS2 inherited homozygous mutation could be a critical event in GBM formation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1846.
Abstract 185: Protein expression of DNMT1, DNMT3a, and DNMT3b in human hepatocellular carcinoma
Authors: Endo Kanenori , Miyake Takanori , Honjo Soichiro , Tsujitani Shunichi , Hirooka Yasuaki , Ikeguchi Masahide 
Published: February 2011

Abstract
Background/Aims: DNA methylation plays an important roles in the regulation of gene expression. Gene silencing by aberrant hypermethylation of CpG islands in gene promoter regions in frequently found in human cancers. By the assistance of DNA methyltransferases (DNMTs), methyl groups are transferred to promoter CpG islands, many tumor suppressor gene can be silenced by promoter CpG islands methylation. However, studies on DNMTs in hepatocellular carcinoma (HCC) are rare, and there are no immunohistochemical studies on the correlations with these expressions and HCC patient's suvival.
Methods : We immunohistochemically examined the expression of DNMT1, DNMT3a and DNMT3b and the relationships between these expressions and histological grade, clinicopathological parameters and patient's survival in 95 patients with HCC.
Results : DNMT1, DNMT3a and DNMT3b immunoreactivities were presented in nuclei of HCC cells. In the tumorous lesion, the number of positive immunoreactivities was 95/95 (100%) for DNMT1, 87/95 (92%) for DNMT3a and 81/95 (85%) for DNMT3b. The degree of each protein expression significantly correlated with tumor differentiation and intrahepatic metastasis, and only DNMT3a protein expression significantly correlated with portal vein imvolvement of tumor. Though there were no relations between the DNMTs expression and tumor size, over-expressions of DNMT3a and 3b proteins were associated with poor prognosis of HCC's patients. Moreover, the overall survival rate of patients group that showed over-expression of three DNMTs in tumorous lesion was significantly lower than it of other patients groups.
Conclusion : DNMTs are involved in HCC progression, and their overexpression is associated with poor prognosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 185.
Abstract 1851: Investigation of the Birt-Hogg-Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer
Authors: Nahorski Michael S. , Lim Derek Hk , Martin Lynn , Gille Johan JP , Mckay Kirstin , Rehal Pauline K. , Ploeger Martijn , van Steensel Maurice , Tomlinson Ian P. , Latif Farida , Menko Fred H. , Maher Eamonn R. 
Published: February 2011

Abstract
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially to be part of the BHD phenotype, some recent studies have not confirmed this association. We undertook a series of clinical and laboratory studies to investigate possible relationships between colorectal neoplasia and the BHD gene (FLCN). Thus we investigated whether individuals with familial colorectal cancer of unknown cause might have unsuspected germline FLCN mutations, looked for somatic FLCN C8 tract mutations in microsatellite unstable sporadic colorectal cancers and assessed the risk of colorectal neoplasia and possible genotype-phenotype correlations in BHD patients. Although we found previously that germline FLCN mutations can be detected in ∼5% of patients with familial renal cell carcinoma, we did not detect germline FLCN mutations in 50 patients with familial non-syndromic colorectal cancer. Analysis of genotype-phenotype correlations for two recurrent FLCN mutations identified in a subset of 51 families with BHD demonstrated a significantly higher risk of colorectal neoplasia in c.1285dupC mutation (within the exon 11 C8 mononucleotide tract) carriers than in c.610delGCinsTA mutation carriers (χ2=5.78 P=0.016). Somatic frameshift mutations in the FLCN exon 11 C8 mononucleotide tract were detected in 23% of sporadic colorectal cancers with microsatellite instability suggesting that FLCN inactivation might contribute to colorectal tumourigenesis. Our findings suggest that the previously reported clinical heterogeneity for colorectal neoplasia may reflect allelic heterogeneity and the risk of colorectal neoplasia in BHD syndrome requires further investigation.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1851.
Abstract 1853: Monoclonal B-cell Lymphocytosis (MBL) has increased incidence in non-Hodgkin lymphoma (NHL) Families
Authors: Slager Susan L. , Rabe Kari G. , Achenbach Sara J. , Call Timothy G. , Vachon Celine M. , Habermann Thomas M. , Kay Neil E. , Ansell Stephen M. , Shanafelt Tait D. , Cerhan James R. , Hanson Curtis A. 
Published: February 2011

Abstract
Background. MBL is defined as a monoclonal expansion of B lymphocytes (&lt; 5 × 109/L) in the blood without associated lymphadenopathy or organomegaly; MBLs with a chronic lymphocytic leukemia (CLL) immunophenotype have been termed as CLL-like MBL. The prevalence of CLL-like MBL in the general population is 3.5-12% but increases with age; however, the frequency is even higher (∼13-18%) among unaffected relatives from CLL families (i.e., families with two or more CLL members). We and others have found that a small proportion of individuals with CLL-like MBL individuals and lymphocytosis will progress to CLL requiring treatment (∼1.1% per year). Because CLL and NHL have been shown to aggregate together within families, suggesting a shared pathogenesis, we evaluated the frequency of MBL in NHL families.
Methods. Individuals were obtained from an ongoing study of NHL families (i.e., families with 2 or more NHL members). However, we limited to NHL families with at most 1 individual with CLL due to the known increased frequency of MBL in CLL families. Multi-color flow cytometry was performed on fresh peripheral blood samples. A CBC and differential count was simultaneously obtained using an automated blood cell counter. Five possible flow diagnoses were defined as: CLL-like MBL (CD5+CD20dim), atypical MBL (CD5+CD20bright), non-CLL like MBL (CD5−), and normal immunophenotype (NIPT). Medical records of NHL cases were reviewed to confirm disease.
Results. A total of 30 individuals from 16 NHL families had available flow cytometry results. The mean age at flow analysis was 56 years (range 37− 83 years). We identified 5 individuals with MBL from 4 families: 3 of the 6 had CLL-like MBL, 1 had atypical MBL, and 1 had non-CLL like MBL. The remaining 25 individuals had a NIPT. Thus, the MBL rate in NHL families is 17% (5/30). Among the CD5+ MBL (both CLL-like and atypical MBL) individuals, all were female and the mean absolute lymphocyte count was 1.4 × 109/L. Of interest, 1 of the CLL-like MBL individuals is from a family where two members had monoclonal gammopathy of uncertain significance (MGUS).
Conclusion: Our data show that MBLs of various phenotypes can be found at a higher prevalence in NHL families than that of the general population. Further, the frequency of MBL in NHL families is comparable to that of CLL families. Although more work is needed, our results suggest that MBL may be clustering within NHL families, and thus support a possible common inherited predisposition of NHL and CLL, with MBL signifying a shared early pathogenetic step.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1853.
Abstract 186: Methyl binding domain protien 2 (MBD2) promotes epithelial dedifferentiation in breast cancer
Authors: Mian Omar , Ginder Gordon 
Published: February 2011

Abstract
Purpose: Methyl-CpG Binding Proteins (MCBPs) are thought to function as the interpreters of epigenetic information encoded in cytosine methylation. Their ability to translate DNA methylation into local transcriptional repression has sparked interest in the role MCBPs play in cancer. We have studied the function of Methyl-Binding Domain Proteins (MBDs) in human mammary epithelial cancers, where repatterning of CpG methylation is common.
Results: We find Methyl Binding Domain Protein 2 (MBD2) promotes the abnormal multi-cellular morphology characteristic of tumor cells. Stable MBD2 knockdown in MCF7 cells leads to an increased proportion of differentiated epithelial structures (e.g. acinii, 70%, [CI=0.55-0.83]) in 3D culture when compared to untransfected (46%, [CI=0.39-0.53], p ≤ 0.038) or control shRNA transfected (37%, [CI=0.29-0.45], p ≤ 0.012) populations. To identify the genes underlying this MBD2 dependant phenotype, high throughput quantitative PCR data were probed using self organizing map (SOM) analysis. We found only a small subset of the breast cancer specific tumor suppressors known to be silenced by promoter hypermethylation were regulated by MBD2 alone (n=7, 15%). Several genes previously shown (by us and others) to be MBD2 bound by chromatin immunoprecipitation (ChIP) were not induced by MBD2 knockdown, suggesting MBD2 exhibits tumor and tissue-type specificity. Moreover, gene sets activated by the DNA methylation inhibitor, 2-deoxy-5-aza-cytidine (4uM, n=30, 67%), and MBD2 knockdown (n=18, 40%) were different, suggesting pleiotropic activity; for example at loci that exhibit additive induction (n=11, 24%) and those that do not. MBD2 dependant genes were rapidly re-suppressed upon rescue with a shRNA binding site variant MBD2 and ChIP studies confirmed binding of MBD2 at all genes examined within the MBD2 dependant cluster. Transient siRNA mediated knockdown of individual MBD2 dependant genes did not restore the dedifferentiated phenotype, suggesting coordinate regulation by multiple downstream targets of MBD2.
Conclusion: Our studies show MBD2 promotes tumor suppressor silencing and dedifferentiation in breast cancer and intimate a role for MBD2 in fine-tuning mammary epithelial gene expression patterns.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 186.
Abstract 1860: Association of esophageal cancer risk with genetic polymorphisms of xenobiotic metabolizing genes, DNA repair genes, and inflammation-regulating genes in Huaian, China
Authors: Xu Li , Wang Zemin , Tang Lili , Wang Shaokang , Hu Xu , Sun Guiju , Wang Jia-Sheng 
Published: February 2011

Abstract
Accumulating evidences suggest that both exposure to environmental carcinogens and individual susceptibility factors contribute to the formation of esophageal cancer. Huaian City is one of the highest risk areas of esophageal cancer in China with the annual incidence over 100/100,000 people. To explore etiological risk factors contributing to the high rate of esophageal cancer, a population-based case-control study was conducted in 185 esophageal squamous cell carcinoma (ESCC) cases and 515 age-, gender-, and residency-matched healthy controls in Huaian. Our previous study found an association between dietary fumonisin exposure and ESCC risk in this population. In the present study, we further investigated the association between ESCC and polymorphic genes involving in xenobiotic metabolizing activities, DNA repair, and inflammation regulation including GSTM1, GSTT1, XPD (Lys751Gln), hOGG1 (Ser326Cys), TNF-α (G308A), NF-κB (−94ins/delATTG), COX-2 (G765C), and iNOS (Ser608Leu). Genetic polymorphisms of GSTM1 and GSTT1 were determined by multiplex PCR and other polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP) analysis using genomic DNA samples obtained from lymphocytes of study subjects. The prevalence of GSTT1 null genotype was significantly higher in cases (53.51%) than in controls (41.94%) (p=0.0067), with an age- and gender-adjusted odds ratio (OR) of 1.68 and 95% confidence interval (CI) of 1.18 − 2.39. After stratifying by gender, GSTT1 null type was found more prevalent in male cases (57.14%) than in male controls (42.64%) (p=0.0117). XPD Lys751Gln polymorphism was associated with increased ESCC risk (age- and gender-adjusted OR=1.74, 95% CI: 1.11-2.74). XPD heterozygous and mutant genotypes (Lys/Gln+Gln/Gln) were more prevalent in cases (20.54%) than in controls (14.26%) (p=0.0453), and in female cases (24.32%) than in female controls (13.01%) (p=0.0187). Heterozygous genotype of TNF-α was found in 12.97% of cases and 7.65% of controls, showing a marginal increased risk of ESCC (adjusted OR=1.68, 95% CI: 0.95-2.98). These results suggest that polymorphisms of GSTT1, XPD and TNF-α gene may contribute to ESCC risk in this high-risk population. (Supported by NIH/NCI grants, CA94683 and CA90997).
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1860.
Abstract 1866: Polymorphisms in DNA double-strand break repair genes and end-joining capacity from sisters discordant for breast cancer from the New York site of the BCFR
Authors: Wu Hui-Chen , Machella Nicola , Wang Qiao , Senie Ruby T. , Santella Regina M. , Terry Mary Beth 
Published: February 2011

Abstract
Dysfunction in DNA double strand break (DSB) repair increases breast cancer risk. Genetic variation could be an important factor in determining DSB capacity. However, data on the association of single nucleotide polymorphisms (SNPs) of DSB repair genes with phenotype and with breast cancer risk are limited. We determined genotypes for 25 DSB repair SNPs in a total of 298 families with discordant sisters for breast cancer, including 85 families with end-joining (EJ) capacity data available from the New York site of the Breast Cancer Family Registry (BCFR). We observed that XRCC4 variant (rs1056503) was associated with increased breast cancer risk with age-adjusted odds ratios (OR) of 1.67 (95% confidence interval (CI)=1.02-2.74) and a significant inverse effect of an XRCC5 variant (rs1051677) with an age-adjusted OR of 0.07 (95% CI=0.009-0.58). EJ capacities differed by different genotypes of BRCA1 among controls, and different genotypes of XRCC5 among cases and controls. However, in a final multivariable conditional logistic model, including RAD52 (rs11226), XRCC4 (rs1056503) and XRCC5 (rs3834), we did not observed any statistically significant genetic effect of DSB repair genes on breast cancer risk. Although these findings suggest that selected polymorphisms of DSB pathway genes were associated with EJ capacity, there were no main associations with breast cancer suggesting that DSB phenotype rather than genotype may be more important in predicting breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1866.