bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 910: Isothiocyanate-gene interactions and endometrial cancer risk: the California Teachers Study
Authors: Horn-Ross Pamela L. , Canchola Alison J. , Bernstein Leslie , Van Den Berg David , Ursin Giske 
Published: February 2011

Abstract
Background: Cruciferous vegetables may reduce the risk of endometrial cancer, although the evidence is mixed. However, as observed for other cancers, this association may be modified by polymorphic variation in phase I genes (e.g., CYP1A1 which also controls estrogen metabolism) and phase II genes (e.g., GSTs). Such interactions have not been previously examined for endometrial cancer.
Methods: A nested case-control study of type 1 invasive endometrial cancer was conducted within the California Teachers Study (CTS) cohort. 320 women (age≥50) with incident cancer, identified through the California Cancer Registry and diagnosed after joining the cohort and before January 2005, and 629 controls, frequency-matched on age, race/ethnicity, and broad geographic region of residence within California, provided a DNA sample and had complete epidemiologic data. Consumption of cruciferous vegetables was assessed using a validated food-frequency questionnaire at the time women joined the cohort in 1995-96. Isothiocyanate (ITC) consumption was estimated using values obtained from prior analysis of California foods and was based on frequency and portion size of usual consumption of cruciferous vegetables. Selected single nucleotide polymorphisms (SNP) in several phase I and II genes were genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for matching variables.
Results: Neither cruciferous vegetable or ITC intake, nor variants in CYP1A1 MspI (rs4646903), GSTM1, or GSTT1 were directly associated with endometrial cancer risk. The Val/Val genotype of GSTP1 Ile105Val was associated with increased endometrial cancer risk (OR=1.64, 95% CI: 1.07-2.53) and the Val/Val genotype of CYP1A1 Ile462Val was associated with reduced risk (OR=0.63, 95% CI: 0.37-1.08). There was no interaction, however, between cruciferous vegetable or ITC intake and any of these genes.
Conclusion: Consistent with some, but not all, previous studies we observed a significant reduction in risk associated with the Val/Val genotype of CYP1A1 Ile462Val. This study also confirms a single previous, but smaller report of an association between type I endometrial cancer and the Ile105Val SNP in GSTP1. However, while the prospective assessment of dietary intake minimizes recall bias, we found no evidence of an interaction between these genetic variants and ITC consumption.
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 910.
Abstract 913: 5,10-Methylenetetrahydrofolate reductase C677T allele frequency and childhood leukemia incidence in predominantly European ancestry countries
Authors: Johnson Kimberly J. , Spector Logan G. 
Published: February 2011

Abstract
5,10-Methylentetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been intensely studied as cancer susceptibility alleles. For childhood leukemia, data have indicated that the most commonly studied MTHFR SNP, C677T, is associated with a slightly reduced risk of acute lymphoblastic leukemia (ALL). Both childhood leukemia incidence and MTHFR allele frequencies show variation worldwide. Our objective was to conduct an ecologic study to determine whether the MTHFR C677T allele frequency and childhood leukemia incidence are associated. We used cancer incidence data collected by the International Agency for Cancer Research from 22 registries that captured 19,025 leukemia cases diagnosed between the ages of 0 and 14 years from the United States, Canada, Australia, and 18 European countries; data were restricted to registries with majority European ancestry populations in order to minimize confounding by ancestry. MTHFR allele frequencies were gathered from the literature to match as closely as possible the registry populations. We modeled the association between childhood leukemia incidence and MTHFR C677T allele frequency using Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs). Estimates of the minor C677T allele frequency ranged from 24% in Finland to 44% in Italy. There was a weak inverse correlation between leukemia incidence and MTHFR C677T allele frequency (r=0.19), that was stronger for ALL (r=0.30). Acute nonlymphoblastic leukemia (ANLL) incidence was positively correlated with MTHFR C677T allele frequency (r=0.36). Poisson regression results from linear models showed that the incidence of childhood leukemia decreased by 5% (95% CI 3%-6%) for every 5% increase in the C677T allele frequency. A similar pattern was observed for ALL with a RR of 0.93 (95% CI=0.92-0.95) but not acute non-lymphoblastic leukemia (ANLL) (RR=1.04, 95% CI=1.00-1.07). The significant inverse associations between the C677T allele frequency and leukemia and ALL incidence were specific to incidence rates for children diagnosed &lt;10 years. These results are consistent with the results of case-control studies of the association between childhood leukemia and MTHFR allele frequency suggesting a modest risk reduction in association with the C677T allele. The strengths and limitations of ecological vs. case control study designs will be discussed in the context of these results to provide insight into the causal relationship between the MTHFR minor allele frequency and childhood leukemia risk.
This research was supported by NIH grant T32 CA099936.
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 913.
Abstract 918: Glucuronidation genotypes and nicotine metabolic phenotypes: Importance of UGT2B10 and UGT2B17 knock-out polymorphisms
Authors: Chen Gang , Giambrone Nino E. , Dluzen Doug , Blevins-Primeau Andrea S. , Gallagher Carla , McCloskey Diane , Lazarus Philip 
Published: February 2011

Abstract
Glucuronidation is an important pathway in the metabolism of nicotine, with ∼28% of urinary nicotine metabolites in the form of glucuronidated compounds. Recent in vitro studies have suggested that the UGTs 2B10 and 2B17 play major roles in nicotine glucuronidation with polymorphisms in both enzymes shown to significantly alter the levels of nicotine-, cotinine-, and trans-3-hydroxy-cotinine (3HC)-glucuronides in human liver microsomes in vitro. In the present study, the relationship between the levels of urinary nicotine metabolites and functional polymorphisms in UGTs 2B10 and 2B17 were analyzed in urine specimens from 104 Caucasian smokers. The levels of nicotine-glucuronide and cotinine-glucuronide were 47 (p&lt;0.0005) and 47% (p&lt;0.0001) lower, respectively, in urine from smokers exhibiting the UGT2B10 (*1/*2) genotype, and 98 (p&lt;0.0001) and 99 (p&lt;0.0001), respectively, in urine from smokers with the UGT2B10 (*2/*2) genotype, as compared to the urinary levels in wild-type UGT2B10 smokers. The levels of 3HC-glucuronide was 64% (p&lt;0.0001) lower in the urine from smokers exhibiting the homozygous UGT2B17 (*2/*2) deletion genotype as compared to the levels in urine from wild-type UGT2B17 subjects. These data are consistent with previous in vitro studies and demonstrate that UGTs 2B10 and 2B17 play important roles in the glucuronidation of nicotine, cotinine and 3HC in vivo, and suggest the UGT2B10 codon 67 SNP and the UGT2B17 deletion significantly reduce overall glucuronidation rates of nicotine and its major metabolites in smokers.
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 918.
Abstract 925: Common variants in genes related to immune response and childhood leukemia risk
Authors: Han Sohee , Lan Qing , Park Ae Kyung , Lee Kyoung-Mu , Park Sue K. , Ahn Hyo Seop , Shin Hee Young , Kang Hyoung Jin , Koo Hong Hoe , Seo Jong Jin , Choi Ji Eun , Ahn Yoon-Ok , Chanock Stephen J. , Kim Ho , Rothman Nathaniel , Kang Daehee 
Published: February 2011

Abstract
Objective: In order to investigate possible genetic contribution to childhood leukemia in the immune system, we evaluated the associations between 786 SNPs in 68 genes/gene regions related to immune response and childhood leukemia risk.
Methods: Incident childhood leukemia cases (n=136) and non-cancer controls (n=254) were recruited from three teaching hospitals in Seoul between 2003 and 2006. Candidate genes/gene regions were selected based on SNP databases (CGAP and SNP500 database), and genotype assay was performed using GoldenGate (Illumina) oligonucleotide pool assay (OPA). First, we selected SNPs with dose response effect (Ptrend&lt;0.001). The 16 SNPs deemed unusable due to failure of genotyping or monomorphism (9 SNPs), low yield (2 SNPs), HWE p &lt;0.001 (5 SNPs) in each case and control were excluded from the analysis. A gene-level minP was computed using a permutation-based re-sampling procedure (10,000 permutations) taking all SNPs in each gene/gene region into account. We considered minP &lt;0.05 as noteworthy. Childhood leukemia risk was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, gender and birth weight.
Results: Among the 786 SNPs, 134 SNPs in 7 genes/gene regions were significantly associated with childhood leukemia risk (Ptrend &lt;0.001). Five out of 7 genes/gene regions of immune response (MDM2 (murine double minute 2), CD81 (CD81 molecule), IL-2 (interleukin 2), TNF/LTA (tumor necrosis factor-a (TNF) and lymphotoxin-a), RELB (v-rel reticuloendotheliosis viral oncogene homolog B)) were significantly associated with childhood leukemia risk (minP &lt;0.01).
Discussion: Our results suggest that genetic polymorphisms in immune regulatory may play a role in childhood leukemia development. Further large study is warranted confirm our findings.
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 925.
Abstract 937: Nicotinic acetylcholine receptor polymorphisms, secondhand smoke and lung cancer risk
Authors: Asomaning Kofi , Zhai Rihong , Sheu Chau-Chyun , Heist Rebecca , Chen Feng , Liu Geoffrey , Su Li , Lin Xihong , Christiani David 
Published: February 2011

Abstract
Introduction: Passive or secondhand smoke (SHS) exposure is an independent risk factor for adult non-small cell lung cancer (NSCLC). In 2008, three genome wide association studies (GWAS) identified a locus on chromosome region 15q24-25.1 that was strongly associated with lung cancer. In this study, we assessed the interaction of the two most significant single nucleotide polymorphisms (SNPs) reported (rs8034191, rs1051730) with SHS on lung cancer risk. We hypothesize that after adjusting for active cigarette smoking, individuals with the risk alleles and the highest cumulative exposure to SHS are at the greatest risk of lung cancer.
Methods: This study population is derived from a large ongoing case control study evaluating the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital. The polymorphisms were genotyped by the 5V nuclease assay (Taqman) using the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA). Interviewer-administered questionnaires collected information on demographics, and detailed smoking histories from each subject. Second hand smoke exposure duration and frequency was self-reported for three different activities (leisure, work and at home). The cumulative SHS exposure was the sum of all durations multiplied by their frequency weight. We used the co-dominant genetic model for individual SNPs, controlling for age, gender, pack years, years since smoking cessation and smoking status. We tested for interaction using the Likelihood Ratio Test by incorporating cross product interaction terms of indicator variables for each SNP and quartiles of cumulative exposure.
Results: A total of 2071 cases and 1506 controls were analyzed. Among cases, exposure to SHS at home 1924(93%), work 1727 (83%), leisure 1791 (86%); among controls 1328 (88%), 1044 (69%) and 1233 (82%) respectively. In stratified analysis, for study participants in the highest quartile of cumulative SHS exposure and comparing the homozygous variant to the wildtype, the adjusted odds ratio (AOR) for lung cancer was 1.55 (0.99-2.44) (rs8034191) and 1.66 (1.05-2.62) (rs1051730). In the lowest quartile of SHS exposure the corresponding results were 0.94 (0.47-1.89) (rs8034191) and 0.91(0.45-1.84) (rs1051730). There was no evidence for gene-SHS interaction.
Conclusion: Our results indicate that secondhand smoke does not modify the association of rs1051730 and rs8034191 with non-small cell lung 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 937.
Abstract 939: Chemoprevention of familial adenomatous polyposis by EM011 in the ApcMin/+ mouse model
Authors: Li Shiwang , Ghaleb Amy M. , He Jing , Bughani Usha , Bialkowska Agnieszka B. , Yang Vincent W. , Joshi Harish C. 
Published: February 2011

Abstract
Abstract
Germline mutation of the tumor suppressor gene, adenomatous polyposis coli (APC), is responsible for familial adenomatous polyposis (FAP) with nearly 100% risk for colon cancer at an early age. Although FAP is involved in only 1% of all colon cancer cases, over 80% of sporadic cancers harbor somatic mutations of APC. We show here that 9-bro-noscapine (EM011), a rationally-designed synthetic derivative of a natural non-toxic tubulin-binding alkaloid−noscapine, that reduces the dynamics of microtubules, causes a reversible G2/M arrest in wild type mouse embryonic fibroblasts (MEFs), but an aberrant exit from a brief mitotic block, followed by apoptosis in MEFs isolated from ApcMin/+ mice. Furthermore, both β-catenin levels and activity fell to half the original levels with a concomitant reduction of cell proliferation-inducing cyclin D1, c-Myc, and induction of cytostatic protein p21 prior to caspase-3 activation. Additionally, we show a statistically significant reduction in the number of newly emerging intestinal polyps (to 35% compared with untreated mice) as well as the mean size of polyps (to 42% compared with untreated mice) in EM011-treated ApcMin/+ mice as compared to their sham-treated control littermates. The remaining polyps in the EM011 treated group of ApcMin/+ mice showed evidence of elevated apoptosis as revealed by immunohistochemistry. We failed to detect any evidence of histopathological and hematological toxicities following EM011 treatment. Taken together, our data are persuasive that a clinical trial of EM011 is possible for the prevention/amelioration of polyposis in FAP patients.
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 939.
Abstract 944: Preventive effects of UV radiation and dietary vitamin D on autochthonous murine mammary tumors
Authors: Davari Parastoo , Gorouhi Farzam , Green Jeffrey E. , Epstein Ervin H. 
Published: February 2011

Abstract
Epidemiologic studies support an inverse correlation between solar UV radiation and breast cancer incidence and mortality, a matter of some concern in a society being urged to avoid sun exposure. We assessed directly whether UV radiation of skin has any preventive effect on mammary tumor carcinogenesis in the C3(1)SV40 Tag transgenic mouse. Mice fed diets depleted of vitamin D (+ rescue minerals) were treated with 0 [group A] or 350mJ/cm2 UV 3 times a week without [Group B] or with [Group C] topical 7-dehydrocholesterol, the precursor of cutaneous vitamin D3. Control mice were fed an otherwise identical diet but containing normal levels of vitamin D (1,000IU/kg + rescue minerals) [Group D]. We also fed mice a separate diet containing high (20,000IU/kg) [Group E] or normal (1,000IU/kg) [Group F] vitamin D. We examined mice and excised all palpable tumors (“lumpectomies”) every two weeks at ages 16-28 weeks. Blood was collected at the end of the study. Analyses were performed using Krusskal Wallis test, Mann Whitney test, Spearman's test, life table survival analysis, and log rank test. Circulating 25-hydroxyvitamin D3 (25D3) levels in 59 mice, measured in ng/mL [median (interquartile range)] in groups A-F were 3.0(1.0) 34.0(26.3), 26.0(18.0), 28.0(13.0), 121.0(82.5), and 42.0(15.5), respectively (p&lt;0.001). We found no significant correlation among groups between 25D3 levels and tumor number, mean size, or total tumor volume/mouse. Mice fed the vitamin D depleted diet had a tumor burden that was reduced by UV radiation or by addition of dietary vitamin D, and UV-treated mice had a longer tumor free survival than did the D-depleted mice not so treated. By contrast, the high vitamin D diet, despite tripling the circulating 25D3 level, by comparison to the control diet did not influence mammary tumor number or size or tumor free survival. We interpret these data to suggest that although UV can inhibit development of autochthonous murine mammary tumors, the failure of tumor development to correlate strictly with circulating 25OH D3 levels suggests that its effects may be mediated in part by non-obvious pathways and/or that the anti-mammary cancer effects of vitamin D may plateau.
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 944.
Abstract 955: n-3 polyunsaturated fatty acids promote apoptosis in oxidatively stressed transgenic mouse models
Authors: Fan Yang-Yi , Toyokuni Shinya , Callaway Evelyn S. , Ran Qitao , Lupton Joanne R. , Chapkin Robert S. 
Published: February 2011

Abstract
Colorectal cancer is the second most common cause of cancer death in the United States. An increase in reactive oxygen species (ROS) generated from oxidative stress is generally associated with abnormal cancer cell growth and reflects a disruption of redox homeostasis. Manganese superoxide dismutase (SOD2) and glutathione peroxidase 4 (Gpx4) are two of the most important antioxidant defense enzymes that protect cells against oxidative stress. Interestingly, we have recently demonstrated that n-3 polyunsaturated fatty acids (PUFA) enhance apoptosis, a useful marker of colorectal cancer risk, in colonocytes by enhancing phospholipid oxidation. In order to elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, we fed SOD2het, Gpx4het and Gpx4 over-expressing (Gpx4TG) transgenic mouse models diets containing either n-3 or n-6 PUFA (control). Animals were fed diets containing either 15% corn oil by weight (CO, enriched in n-6 PUFA) or 3.5% CO + 11.5% fish oil (FO, enriched in n-3 PUFA) for 4 wk. Apoptotic cells in the distal colon were enumerated in situ. Relative to their respective wild type siblings, Gpx4het and SOD2het mice had significantly (P&lt;0.05) enhanced levels of colonocyte apoptosis, 63% and 20%, respectively. In contrast, apoptosis in Gpx4TG mice was significantly (P&lt;0.05) reduced by 16% compared to wild type siblings. FO vs CO feeding further increased (P&lt;0.05) apoptosis in Gpx4het and SOD2het mice by 42% and 18%, respectively. In addition, n-3 PUFA elevated apoptosis in Gpx4TG mice back to a level comparable with wild type (control) siblings. These data indicate that dietary and/or genetic pre-deposition to oxidative stress facilitates apoptosis in the colon, thereby reducing colon cancer risk. Supported in part by NIH grants CA59034, CA129444, P30ES09106, and USDA 2008-34402-19195, “Designing Foods for Health” through the Vegetable & Fruit Improvement Center.
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 955.
Abstract 959: Sulindac resistant colon tumors possess an altered molecular phenotype
Authors: Greenspan Emily J. , Nichols Frank C. , Rosenberg Daniel W. 
Published: February 2011

Abstract
Although non-steroidal anti-inflammatory drugs (NSAIDs), including sulindac, have been used extensively as chemopreventive agents for colorectal cancer (CRC), results are not consistent. NSAIDs, most reportedly sulindac, often do not cause a complete regression of adenomas and some patients develop resistance to NSAID treatment. In this study we evaluated the effect of sulindac on colon tumorigenesis in the ApcMin/+ mouse model. Sulindac (180 ppm) given in drinking water for 9 weeks to ApcMin/+ mice significantly reduced the size of colon tumors, but actually caused an increase in colon tumor multiplicity relative to untreated controls (average of 5.5 vs. 1.6 tumors/mouse, respectively; P&lt;0.0001). This indicated that the drug could inhibit colon tumor progression but not initiation. In the small intestine, sulindac significantly reduced tumor size and multiplicity relative to untreated controls (average of 2.3 vs. 42.0 tumors/mouse, respectively; P&lt;0.0001). Generation of a panel of prostanoids was comparably suppressed in the small intestine and colon by sulindac treatment. Sulindac is also known to have many non-COX targets, including p21, β-catenin, E-cadherin, mitochondrial apoptotic proteins and PPARγ. Our goal was to determine whether alterations in these cellular mediators might be responsible for the observed increase in tumor multiplicity in the colon. We found that sulindac treatment protected against E-cadherin loss in colon tumors, with associated inhibition of nuclear β-catenin accumulation. Importantly, p21WAF1/cip1 and PPARγ expression were absent in colon tumors from sulindac-treated mice, suggesting that loss of these proteins is necessary for lack of response to sulindac. Together, these observations may be translatable to designing novel clinical therapies utilizing combinations of agents that target multiple molecular pathways to overcome sulindac resistance.
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 959.