bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 912: Soy isoflavone intake, MDM2 gene polymorphism and breast cancer risk among Chinese women in Singapore
Authors: Koh Woon-Puay , Wang Renwei , Van Den Berg David , Yuan Jian-Min , Yu Mimi C. 
Published: February 2011

Abstract
Epidemiologic studies among populations that consume moderate to high amount of soy have shown that soy isoflavones may reduce breast cancer risk, and the chemopreventive effects are postulated to be related to the anti-estrogenic properties of soy isoflavones. Recently, experimental studies have revealed that dietary isoflavones may also down-regulate the expression of the MDM2 oncogene, and the inhibition of the expression of the MDM2 oncoprotein has in turn been associated with antitumor activities in breast cancer models. Furthermore, a polymorphism in the promoter region of MDM2 SNP309 (T&gt;G change at nucleotide 309 in the first intron; rs2279744) leads to increased expression of the oncogene and has been associated with earlier onset of breast cancer. We have previously shown that postmenopausal women with a higher than median intake of soy have a reduced risk of breast cancer compared with those with a lower intake. If down-regulation of the MDM2 oncogene is one of the mechanistic pathways for the chemopreventive effects of soy isoflavones in breast cancer, we postulate that the protective effect of soy isoflavones on breast cancer will be stronger in those possessing the high-activity MDM2 genotype. To confirm this hypothesis, we conducted a nested case-control study among 281 incident, postmenopausal breast cancer cases and 462 postmenopausal control subjects within the Singapore Chinese Health Study Cohort. Overall, there was no significant association between MDM2 gene polymorphism and breast cancer risk. Postmenopausal women who had a higher than median intake of soy had a reduced risk of breast cancer [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.56-1.03]. This inverse association was principally noted among women homozygous for the high activity MDM2 allele (GG genotype). There was a statistically significant, roughly 50% reduction in breast cancer risk between above versus below median level of soy consumption in this subgroup of women (OR, 0.52; 95% confidence interval, 0.28-0.98). On the other hand, a much weaker, and statistically nonsignificant association was noted among women possessing the lower-activity MDM2 genotypes (OR, 0.86, 95% CI, 0.59-1.24). Our findings suggest that the ability of soy isoflavones to down-regulate the MDM2 oncoprotein may be one etiologic mechanism through which the intake of soy is associated with breast cancer protection.
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 912.
Abstract 915: Xenobiotic metabolizing gene variants, occupational chemical exposures, and renal cell cancer
Authors: Heck Julia E. , Lee Yuan-Chin A. , McKay James D. , Hung Rayjean J. , Karami Sara , Gaborieau Valerie , Szeszenia-Dabrowska Neonila , Zaridze David G. , Lissowska Jolanta , Rudnai Peter , Mates Dana , Foretova Lenka , Janout Vladimir , Bencko Vladimir , Chow Wong-Ho , Rothman Nathaniel , Moore Lee E. , Brennan Paul , Boffetta Paolo 
Published: February 2011

Abstract
The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer. Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer.
The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case-control study conducted between 1998 and 2003 across seven centers in central and eastern Europe. The study centers were in the Czech Republic (Ceske, Prague, Olomouc, Brno), Poland (Lodz), Romania (Bucharest), and Russia (Moscow). Incident cases of primary kidney cancer were recruited and underwent an in-person interview in which detailed data were collected on demographics as well as work history and occupational exposure to chemical agents. Genes (cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT)) were selected for the present analysis based on their putative role in xenobiotic metabolism. Genotyping (874 cases and 2396 controls) was conducted with a GoldenGate® Oligo Pool All (OPA) assay by Illumina® and the 5’ nuclease assay (Taqman, Applied Biosystems). Haplotypes were calculated using fastPhase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusted for country of residence, age, and sex.
We observed an increased risk of renal cell cancer (RCC) with two NAT1 SNPs (NAT1A40T, OR=1.36, CI 1.00, 1.86; NAT1R187Q, OR=1.65, CI 1.01, 2.71) and with CYP1B1V432L (OR=1.14, CI 1.01, 1.28). The slow (NAT1*14) phenotype was associated with increased risk of RCC (OR=1.69, CI 1.00-2.86) in comparison to normal phenotype (NAT1*4, *3, *11). Among persons with NAT1*14 phenotype, occupational exposure to trichloroethylene (OR=9.94, CI 1.15, 86.1) and chlorinated solvents (OR=9.79, CI 1.13, 84.8) conferred an increased risk of RCC. Among those with the CYP1B1V432L variant, occupational exposure to trichloroethylene (OR=1.68, CI 1.21, 2.34) and chlorinated solvents (OR=1.58, CI 1.14, 2.19) also had increased risk of RCC.
These results require replication, but provide evidence that the relationship between certain agents and RCC may be modified by particular variants in xenobiotic metabolism genes.
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 915.
Abstract 917: Polymorphic analysis of MUC4 minisatellites and its relation to cancer
Authors: Lee Se-Ra , Yoon Se-Lyun , Ahn Myoung-Hyun , Chu In-Sun , Leem Sun-Hee 
Published: February 2011

Abstract
The membrane-bound mucins belong to O-glycoproteins family and they are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signalling and in modulating biological properties of cancer cells. Among them, MUC4 is well characterized and their altered expression in cancer indicates an important role for these membrane-bound mucins in tumour progression and metastasis; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified seven novel minisatellites from the entire MUC4 region and investigated how allelic variation in these minisatellites may affect susceptibility to cancers. We analyzed genomic DNA from the blood of normal healthy individuals and five (MUC4-MS2, MS3, MS4, MS6, MS7) among the seven minisatellites exhibited polymorphism. Furthermore, a case-control study was performed that compared genomic DNA from 351 cancer-free controls with DNA from individuals with 352 gastric cancers. A statistically significant association was identified between long alleles of MUC4-MS3 and the odds of gastric cancer: odds ratio (OR), 1.3; 95% confidence interval (CI), 1.02-1.59; and p = 0.03. Moreover, MUC4-MS3 alleles showed the highest heterozygosity (h = 0.74) among seven minisatellites that may play a role in its chromosomal instability. This idea was examined by comparing the polymorphic alleles of hypervariable MUC4-MS3 minisatellites in the blood and cancer tissues from 36 patients with gastric cancer and 27 patients with liver cancer. The frequency of rearrangement in MUC4-MS3 was shown each as 27% and 11% in gastric and liver cancer tissues. Furthermore, these rearrangements were detected significantly higher in long alleles than in short alleles. These observations suggest that the long MUC4-MS3 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC4 function in cancer cells.
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 917.
Abstract 919: The influence of haplotype of interleukin-10 gene on the susceptibility and clinical outcome of non-Hodgkin lymphoma
Authors: Eom Hyeon-Seok , Han Mi Hwa , Park Sohee , Park Weon-Seo , Yun Tak , Kim Hyun-Ju , Sun-Young Kong 
Published: February 2011

Abstract
Background: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, and single-nucleotide polymorphisms (SNP) of this gene have been reported to affect transcription and production of IL-10. Although the association between SNP and Non-Hodgkin lymphoma (NHL) and increased serum IL-10 levels in NHL patients than controls have been known, there were a few reports in context of haplotypes of whole IL-10 gene. In this study, we investigated the association between haplotype of IL-10 gene and the risk of NHL. Moreover, we investigated the association between IL-10 haplotype, and the overall survival and prognostic factors.
Methods: A total of 209 NHL patients and 418 sex- and age- matched controls was included in this study. Through database searching 4 tagging SNPs covering 2.6 kb of IL-10 gene (rs3021094, rs1554286, rs1800872, and rs1800896) were selected considering ethnicity. Analysis was done using TaqMan probe or sequencing. Haplotype and linkage disequilibrium (LD) was analyzed by PHASE and Haploview program. We compared each genotype or haplotype frequency in controls with that in patients. Genotype was tested for its association with overall survival, clinical characteristics (e.g., cell lineage) and international prognostic indices including age, performance, LDH, stage and extra-nodal involvement.
Results: All studied SNP were in Hardy-Weinburg equation in controls. There is no strong LD between four SNPs with r2 ranged from 0.002 to 0.211. Among 15 haplotypes identified by PHASE analysis, haplotype 1 (Ht1, TATT at rs3021094, rs1554286, rs1800872, and rs1800896) composed with all of dominant polymorphisms showed a significantly increased risk for developing NHL with odds ratios (OR) of 2.08 [95% confidence interval (CI); 1.47-2.96] and 5.17 [95% CI; 2.45-10.93] in single or both allele carrier of Ht1 than other haplotypes. There was no significant association between the haplotype of IL-10 and risk factors of NHL. Furthermore, Ht1 was shown to be associated with a significantly worse overall survival in patients with diffuse large B cell lymphoma (DLBCL) with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone, n=37) chemotherapy done before introduction of rituximab therapy (p=0.04), while not significant in patients treated by R-CHOP (Rituximab plus CHOP, n=86) chemotherapy (p=0.27).
Conclusions: This study showed that the IL-10 haplotype is a susceptibility marker for the development of NHL, and it was a significant prognostic indicator for DLBCL patients treated with CHOP. However, IL-10 haplotype was not a risk factor in DLBCL patients treated with R-CHOP.
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 919.
Abstract 923: Association of TGF-β1 genetic variants with HPV16-positive oropharyngeal cancer
Authors: Li Guojun , Sturgis Erich M. , Lei Dapeng , Zhang Yang , Wei Qingyi 
Published: February 2011

Abstract
Purpose: Transforming growth factor-β1 (TGF-β1) plays an important role in inflammation and immune responses, which control the HPV clearance and escape of immune surveillance, and may contribute to genetic susceptibility to HPV16 infection.
Experimental Design: In this case series study, we analyzed the HPV16 status in tumor specimens and genotyped three TGF-β1 polymorphisms using genomic DNA from blood of 200 squamous cell carcinoma of the oropharynx (SCCOP). We calculated odds ratio (OR) and 95% confidence intervals (CIs) in univariate and multivariable logistic regression models to examine the association between the TGF-β1 polymorphisms and HPV16 status in SCCOP.
Results: Compared with those with the common homozygous genotype, the TGF-β1 T869C variant genotypes were significantly associated with HPV16-positive tumor status among patients with SCCOP (OR, 1.97; 95% CI, 1.03 − 3.76) but no significant association was observed for the TGF-β1 C509T or G915C polymorphism. However, when all variant genotypes were combined, SCCOP patients carrying genotypes with any of these TGF-β1 variant were more than twice as likely to have an HPV16-positive tumor (OR, 2.28; 95% CI, 1.16-4.50) as patients with no variant genotypes. When stratified by demographic and clinical characteristics, those under 54 years of age, non-Hispanic white patients, never smokers, and never drinkers with any variant TGF-β1 genotypes were also more likely to have HPV16-positive tumors. Conclusions: TGF-β1 polymorphisms may serve as a susceptibility marker for tumor HPV16 status among SCCOP patients, particularly those who were never smokers and never drinkers. Large studies are needed to validate our findings.
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 923.
Abstract 930: A simple and inexpensive approach to allelotyping the HLA region in a case-control study of non-Hodgkin lymphoma
Authors: Akers Nicholas K. , Curry John D. , Smith Martyn T. , Conde Lucia , Bracci Paige M. , Skibola Christine F. 
Published: February 2011

Abstract
Background: Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy of B- and T-cells. NHL is the fifth most common cancer in the US and NHL incidence rates are increasing, having doubled since the 1970s. As a result, finding causative factors, whether genetic or environmental, remains an important task.
The human leukocyte antigen (HLA) region has a long track record of genetic association with autoimmune disease. Our group has recently published findings that indicate a genetic link between follicular lymphoma and a locus at chr6p21.33, in the HLA Class 3 region. Extended haplotypes are typical in this region, and the overall data implicate a possible genetic association between NHL and distant, yet linked, HLA alleles.
Due to high genetic complexity, it is difficult to assess allelotype information in the HLA region without using genetic sequencing approaches. However, sequencing is expensive both in terms of dollars and DNA, making it unfeasible for pilot study work. To circumvent these research limitations and quickly and easily explore our hypothesis, we set out to create an assay that is high-throughput, inexpensive, uses minimal DNA, and gives meaningful HLA allelotype information.
Results: Using multiplexed ligation-dependent probe amplification (MLPA) we have developed an assay that is able to obtain specific allelic information for one complex HLA gene. One to two digit, bi-allelic typing requires only 100ng of genomic DNA and can be run on 96-well plates over the course of 2 days. Samples are run through an Applied Biosystems 3730xl capillary DNA analyzer to obtain raw data. Analysis is simple relative to sequencing-based typing approaches; there is no need for expensive computer programs and translating raw data to allelotypes is trivial. Compared to sequencing, this is a very affordable assay that gives broad indications of allele associations, making it an ideal methodology for pilot studies. We are currently applying MLPA technology to screen for HLA allelotypes associated with risk of NHL.
Discussion: MLPA is a useful tool that can be applied to conduct HLA allelotyping. This technology is an economically feasible approach for large-scale genotyping of closely related alleles and represents a key intermediate research tool that is more specific than genome-wide analysis and more affordable than sequencing. This assay may aid in the discovery of key HLA allelotypes associated with lymphoma, as well as help to eliminate false positive results.
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 930.
Abstract 932: Molecular characterization of transcription factors binding to the cancer-related interleukin-1 B gene polymorphisms
Authors: Landvik Nina Elisabeth , Haugen Aage , Zienolddiny Shan 
Published: February 2011

Abstract
Pulmonary inflammation together with chemical exposure may potentiate the carcinogenic process, underlining the importance of inflammation in cancer development. Interleukin-1beta (IL-1β) encoded by the IL1B gene, has been associated with chronic inflammation and plays an important role in lung inflammatory diseases, including COPD and lung cancer. Elevated levels of IL-1β will greatly enhance the intensity of the inflammatory response. There are large inter-individual differences in IL1B gene expression, which may be explained genetically by presence of single-nucleotide polymorphisms (SNPs) scattered throughout the regulatory region (rSNPs) of the gene. These rSNPs may affect IL1B expression by changing the binding affinity of transcription factors or creating novel transcription binding sites. Our studies have shown that several polymorphisms located in the promoter and the enhancer regions of the IL1B gene may affect risk of non-small cell lung cancer. Notably, rSNPs at −3893 G, −1464 G, −511 C and −31 T position formed a specific haplotype (GGCT) with near complete linkage disequilibrium in lung cancer patients, but not in controls where the risk haplotype (GGCT) was present in 65% of cases compared with 36% of controls. The risk haplotype was correlated with significantly higher IL1B mRNA levels in the lung of lung cancer patients. Particularly, we found that the T to C SNP at the −31 position which is located close to the transcription start site of the gene resulted in binding of different transcription factors to the C and T variants. We have further characterized the specific transcription factors binding to the −31 SNP. In DNA-protein interaction studies using Electrophoretic Mobility Shift Assay (EMSA) and human lung epithelial cells we found evidence that the transcription factor Ying Yang 1 (YY1) bound preferentially to the C SNP. The binding of YY1 to the C SNP was further confirmed using Chromatin Immunoprecipitation (ChIP) assay in human lung epithelial cells.
In summary, we have characterized transcription factors that may interact differentially with base changes in the SNPs and thereby may explain the biological effects of the SNPs in modifying the risk to cancer (supported by the Norwegian Cancer Society).
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 932.
Abstract 940: Mucin depleted foci as a biomarker for colon precancerous lesions in estrogen receptor β knockout mice
Authors: Saleiro Diana , Murillo Genoveva , Kopelovich Levy , Mehta Rajendra G. 
Published: February 2011

Abstract
The role of the estrogen receptor β (ERβ) in the colon has received considerable interest, yet in vivo models are needed to better define its protective actions. In the present study, wild-type (WT), ERα and ERβ knockout (αERKO and βERKO) mice were injected with azoxymethane (AOM). Fourteen weeks after the AOM exposure the incidence of aberrant crypt foci (ACF) was assessed by methylene blue staining. βERKO mice showed significantly higher incidence (p &lt; 0.001) of ACF (15.0 ± 5.5) as compared to αERKO (3.4 ± 2.2) and WT (4.6 ± 2.8) mice. The colons in some βERKO mice had increased thickness and loss of normal morphology. It has been reported that ERβ has a role in maintenance of the colonic crypt architecture; this may explain the loss of crypt organization in the colonic epithelium of βERKO mice. The presence of mucin depleted foci (MDF) has been reported, both in humans and in rodents, as an early event in colon cancer. Therefore, in order to surpass the limitations with ACF scoring, we performed alcian blue-neutral red staining to assess the presence of MDF. This staining allowed the assessment of precancerous lesions on all the βERKO mice colons (38.3 ± 8.2; p &lt; 0.001), comparing to WT and αERKO mice (6.9 ± 3.6, and 10.0 ± 4.3, respectively), and served to confirm the ACF results. Together these results support the use of MDF staining as a biomarker for precancerous lesions, and the protective role of ERβ in colon carcinogenesis. (Supported by NIH K01 CA103861, Fulbright Portugal Commission, and FCT (MCET and FSE).
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 940.
Abstract 945: Sca-1 deficiency enhances the chemopreventive activity of a peroxisome proliferator-activated receptorγ (PPARγ) agonist
Authors: Yuan Hongyan , Upadhyay Geeta , Yin Yuzhi , Pollock Claire , Kopelovich Levy , Glazer Robert I. 
Published: February 2011

Abstract
Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored membrane protein that was first identified as a murine marker of activated lymphocytes with stem cell-like properties. Although Sca-1 is widely used to enrich for stem cells in various tissues, little is known about its function and associated signaling pathways in development and tumorigenesis. Therefore, the role of Sca-1 in mammary gland development and tumorigenesis was undertaken using Sca-1 null mice. Sca-1-deficient animals exhibited slower ductal development in an age-dependent manner, and expressed increased p21Cip1 and reduced pRB, as well as a diminished response to progestin and estrogen stimulation. Mammary epithelium from Sca-1-null mice expressed increased PTEN, and reduced PDK1, AKT and c-Src activation. Significantly, the Sca-1 null mammary gland expressed increased PPARγ and reduced PPARδ, which resulted in a 10-fold increase in the ratio of PPARγ to PPARδ. In concordance with this phenotype, Sca-1 null mice exhibited a delay in progestin/DMBA-mediated mammary carcinogenesis, and were highly sensitive to the chemopreventive effects of PPARγ agonist GW7845, where tumorigenesis was inhibited by 90%. In contrast, tumor formation in Sca-1 null mice was unaffected by PPARδ agonist GW501516. Since GPI-anchored receptors are known to be associated with members of the c-Src tyrosine kinase family, we assessed if reduction of Sca-1 by RNAi affected c-Src activity, and if reduced c-Src activity may have contributed to increased GW7845 sensitivity. Lentivirus-mediated expression of Sca-1 shRNA in mammary tumor cells markedly reduced c-Src activation. In contrast, overexpression of c-Src, but not kinase-dead c-Src, inhibited PPARγ-dependent reporter gene activity and associated with PPARγ. These data suggest for the first time that loss of Sca-1 upregulates PTEN, attenuates c-Src and enhances PPARγ agonist sensitivity. Thus, targeting Sca-1 or its human homolog may be a useful approach to amplify the chemopreventive activity of PPARγ agonists.
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 945.