bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2802: Altered expression and the missense polymorphism of the human base excision repair gene NTH1 in gastric cancer
Authors: Goto Masanori , Shinmura Kazuya , Konno Hiroyuki , Sugimura Haruhiko 
Published: February 2011

Abstract
Reactive oxygen species generated in living cells during normal cellular metabolism and in response to exogenous inducers cause the formation of oxidatively damaged bases in DNA. These oxidized base lesions are primarily removed by the base excision repair (BER) pathway. A BER enzyme, NTH1, has activity that is capable of removing oxidized pyrimidines, such as thymine glycol, from DNA. To clarify whether the NTH1 gene is involved in gastric carcinogenesis, we first examined the NTH1 expression level in eight gastric cancer cell lines, and the results showed that NTH1 expression was downregulated in all of them, including cell line AGS. Next, a comparison of excisional repair activity against thymine glycol by empty-vector-transfected AGS clones and FLAG-NTH1-expressing AGS clones showed that a low NTH1 expression level led to low capacity to repair the damaged base in the gastric epithelial cells. Reduced mRNA expression of NTH1 was also detected in 36% (18/50) of primary gastric cancers. Moreover, immunohistochemical analysis revealed that NTH1 was predominantly localized in the cytoplasm in 24% (12/50) of the primary gastric cancers in contrast to the nuclear localization in non-cancerous tissue, suggesting impaired excisional repair ability for nuclear DNA. Next, we found two novel genetic polymorphisms, i.e., c. −163C&gt;G and c. −241_-221del, in the NTH1 promoter region, and a luciferase assay showed that both were associated with reduced promoter activity. However, there were no associations between the polymorphisms and risk of gastric cancer in a gastric cancer case-control study. Next, all the coding exons of the NTH1 gene and their boundary regions in DNAs of 23 Japanese patients with gastric cancer was searched for genetic polymorphisms by direct sequencing. A novel variant, c. −31A&gt;G, and a single nucleotide polymorphism, c.98G&gt;A (Arg33Lys, rs2302172) were detected at an allele frequency of 2.2%, and 4.3%, respectively. However, the c. −31A&gt;G polymorphism did not affect reduction of promoter activity. We are going to reveal functional characterization of c.98G&gt;A and to examine excisional repair activity against new substrates, such as oligonucleotide containing etheno adducts. Our data suggested that downregulation of NTH1 expression, abnormal localization of NTH1 and the missense polymorphism may be involved in the pathogenesis of a subset of gastric cancers.
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 2802.
Abstract 2803: A pooled analysis of circulating 25(OH)D and upper gastrointestinal cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers
Authors: Abnet Christian C. , Chen Yu , Chow Wong-Ho , Gao Yu-Tang , Helzlsouer Kathy J. , Marchand Loic Le , McCullough Marjorie L. , Shikany James M. , Shu Xiao-Ou ,   for the Vitamin D Pooling Project Investigators.
Published: February 2011

Abstract
Upper gastrointestinal (UGI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but are uncommon in Western countries. While it is clear that vitamin D plays important roles in human health, only one prospective study has examined the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and risk of UGI cancers. This study examines the association in eight prospective cohort studies from China, Finland, and the USA that are part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. 25(OH)D concentrations in serum or plasma were measured from 1065 UGI cancer cases and 1066 age-, sex-, race-, and season of blood draw-matched controls. In controls, the median (interquartile range) of circulating 25(OH)D was 39.1 (25.8-56.7) nmol/L, while in cases it was 39.4 (26.3-56.1). 25(OH)D exposure was categorized as six clinically defined categories. A meta-analytic approach showed no significant heterogeneity of effect among the included studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with UGI cancer risk. Compared to the referent group, 50 to &lt;75 nmol/l, those in the lowest (&lt;25 nmol/L) or highest (&gt;=100 nmol/L) categories had odds ratios (95% confidence intervals (CI)) of 0.90 (0.65-1.24) and 0.81 (0.39-1.69), respectively. Subgroup analysis by race showed that among Asians, being in the lowest category was associated with a statistically significant decreased risk of UGI cancer with odds ratio (95% CI) = 0.53 (0.31-0.91) compared to the referent group, but no association in Caucasians, odds ratio (95% CI) = 0.98 (0.67-1.44). Never smokers with concentrations &lt;25 nmol/L were also at lower risk of UGI cancers with odds ratio (95% CI) = 0.55 (0.31-0.96). These results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to lower risk of these highly fatal cancers.
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 2803.
Abstract 281: Insulin-like growth factor II differential activation of the IGF-1 and insulin receptors in African-American and Caucasian breast cancer tissues
Authors: Singh Sharda Kalla , Tan Qianwei , Leon Marino De , Leon Daisy De 
Published: February 2011

Abstract
African-American (AA) women with breast cancer are more likely to have advanced disease at diagnosis, higher risk of recurrence and poorer prognosis than Caucasian (CA) females.
Insulin-like growth factor- II (IGF-II) is a potent mitogen that induces cell proliferation and survival signals through activation of the IGF-I (IGF-IR), insulin (INSR) and hybrid receptors. We hypothesize that differential expression of the IGF1R and INSR isoforms (IR-A, IR-B) between AA and CA women potentiates IGF-II mitogenic effects, thus contributing to the health disparity observed between these ethnic groups. We examined IGF-II, IGF1R and INSR isoforms protein expression and phosphorylation in paired breast tissue samples from AA and CA women by western blot analysis, immunohistochemistry and ELISA techniques. IGF-II expression was significantly higher in AA cell lines and tissue samples when compared to Caucasians. Furthermore, significantly increased expression of IGF1R was observed in AA normal tissues as compared to CA normal tissues, while IGF1R expression was similar between AA normal and malignant tissues. Moreover, AA tumor samples expressed significantly lower levels of IR-B protein than CA tumor samples. IGF1R, INSR, IRS-1 and Shc phosphorylation were significantly higher in AA tumor samples. We conclude that the differential expression and phosphorylation of IGF-II, IGF1R and INSR between AA and CA females coupled with differential activation of downstream signaling pathways may contribute to the increased risk of malignant transformation seen in young AA females, and the more aggressive breast cancer phenotype observed among AA breast cancer patients and represent, along with IGF-II, potential therapeutic targets against health disparities in 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 281.
Abstract 2810: Physical activity and colorectal adenomatous polyps: The Minnesota cancer prevention research unit case-control study
Authors: Tu Huakang , Bostick Roberd M. 
Published: February 2011

Abstract
Background: Although it is well established that greater physical activity is associated with lower risk of colorectal cancer, there have been few studies of its association with adenomatous polyps, precursors of colorectal cancer.
Methods: The 1991-1994 Minnesota Cancer Prevention Research Unit case-control study of 566 colonoscopy-positive adenomatous polyp cases, 687 colonoscopy-negative controls, and 535 community controls investigated the association of physical activity with risk of incident, sporadic colorectal adenomatous polyps. Daily hours of moderate and vigorous physical activity were elicited by a standardized questionnaire and metabolic equivalent (MET) hours were calculated.
Results: The age- and sex-adjusted odds ratios (ORs) for adenomas comparing the highest to the lowest quartile of MET hours were 1.02 (95% confidence interval [CI]: 0.73, 1.44) using colonoscopy-negative controls, and 0.96 (95% CI: 0.69, 1.34) using community controls; after multivariate-adjustment the corresponding ORs were 1.11 (95% CI: 0.77, 1.60) and 1.00 (95% CI: 0.70, 1.43). Analyses stratified by nonsteroidal anti-inflammatory drug (NSAID) use excluding aspirin, adenoma size, and adenoma location did not any yield statistically significant results.
Conclusions: Taken together with the strong, consistent inverse associations of physical activity with colorectal cancer, our null results suggest the possibility that physical activity may be more related to risk for transitioning from colorectal adenoma to carcinoma than to adenoma genesis.
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 2810.
Abstract 2815: Soy increases risk of rectal cancer among Singapore Chinese women
Authors: Butler Lesley M. , Koh Woon-Puay , Wang Renwei , Yuan Jian-Min , Yu Mimi C. 
Published: February 2011

Abstract
Background. Estrogens are thought to play a protective role in colorectal carcinogenesis, however, recent findings for positive associations with circulating estrogens and colorectal cancer risk among postmenopausal women suggest otherwise. Soy isoflavones are phytoestrogens that can display either estrogenic or antiestrogenic properties depending on estrogen receptor signaling, as well as the estrogen milieu. Inconsistent findings for soy and colorectal cancer risk from observational studies may be due to the relatively low and mainly adulthood intake, as well as differences in the estrogen milieu levels in the most studied populations.
Methods. We examined the relationship between soy isoflavone intake and colorectal cancer in a population-based cohort of 61,314 Singapore Chinese men and women that was established between 1993 and 1998. As of December 31, 2007, 1,167 (640 male and 527 female) incident colorectal cancer cases had been diagnosed. Diet was assessed at baseline with a validated 165-item quantitative food frequency questionnaire. We used Cox regression methods to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age at baseline, interview year, dialect group, education level, smoking, alcohol use, body mass index (BMI), physical activity, family history of colorectal cancer and total energy intake.
Results. No association was observed between total soy isoflavone intake and risk of colorectal, colon or rectal cancer, overall or among men. Among women, we observed a 43% increase in rectal cancer risk (HR=1.43; 95% CI: 0.92, 2.21; P for trend = 0.11), comparing 4th to 1st quartile of intake (P for interaction by sex=0.04). The association with soy isoflavones was stronger among women who were postmenopausal at baseline (HR=1.64; 95% CI: 1.03, 2.60; P for trend = 0.01). The associations for rectal cancer among postmenopausal women were similar with individual soy isoflavones, soyfoods and soy protein intake. The estrogen milieu was low among postmenopausal women in our cohort. For example, only 6% reported ever use of exogenous hormones and the median BMI was 23.2 kg/m2.
Conclusion. We report a detrimental effect for dietary soy isoflavones on rectal cancer risk among postmenopausal women. Our finding suggests that in a low estrogen milieu phytoestrogens have procarcinogenic effects in the rectum that require lifelong exposure to relatively high levels of intake.
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 2815.
Abstract 2816: Low-carbohydrate diets and prostate cancer growth: How low is “low enough”
Authors: Masko Elizabeth M. , Thomas Jean A. , Antonelli Jodi A. , Lloyd Jessica C. , Phillips Tameika E. , Poulton Susan H. , Pizzo Salvatore V. , Freedland Stephen J. 
Published: February 2011

Abstract
Introduction: Previous dietary studies indicate carbohydrate intake may influence prostate cancer biology, as LAPC-4 and LNCaP xenograft mice fed a no-carbohydrate ketogenic diet (NCKD; 84% fat-0% carbohydrate-16% protein kcal) had significantly smaller tumors and longer survival times compared to mice fed a Western diet (40% fat-44% carbohydrate-16% protein kcal). The NCKD mice were also found to have higher levels of circulating IGFBP-3 and the lowest levels of insulin, IGF-1, and IGF-1:IGFBP-3 ratio despite consuming more calories than the Western group. As it is nearly impossible for a human to consume and maintain a no-carbohydrate diet similar to that in the previous xenograft studies, we sought to determine whether diets containing 10% or 20% kcal from carbohydrates could slow tumor growth in a similar manner to the NCKD in a xenograft model.
METHODS: A total of 150 male SCID mice were injected with LAPC-4 cells and placed on a Western diet (35% fat-49% carbohydrate-16% protein kcal) ad libitum. Two weeks post-injection, all mice were randomized to one of three arms: NCKD, 10% carbohydrate, or 20% carbohydrate. Ten mice not injected with tumor were fed an ad libitum low-fat diet (12% fat-72% carbohydrate-16% protein kcal) and served as the reference group in a modified-paired feeding protocol for the other three groups. Calorie intake and body weights were measured thrice weekly and tumor volumes twice per week. Mice were sacrificed when tumors reached 1,000mm3.
RESULTS: Despite consuming 5-10% extra calories on average, all mice receiving low-carbohydrate diets were significantly lighter than the mice consuming the low-fat diet (p&lt;0.04). Overall, the mice fed a NCKD were significantly lighter than the other two arms at multiple time points (p&lt;0.05). There were no significant differences in tumor volumes among groups at any time except at Day 52 and 59, where 10% carbohydrate mice had larger tumors (p&lt;0.05). However, after adjusting for the fact that tumor volumes were compared at multiple time points (i.e. multiple comparisons), these were no longer significant. Dietary treatment did not impact overall survival (p=0.34). NCKD mice had significantly higher glucose levels at sacrifice compared to the mice fed 10% and 20% carbohydrates (p=0.001), but similar levels of urinary ketones (p=0.37).
CONCLUSIONS: LAPC-4 xenograft mice fed a low-carbohydrate diet (10-20% carbohydrate kcal) had similar survival to mice consuming a NCKD (0% carbohydrate kcal). Thus, the survival benefit of a NCKD may be achievable with less restrictive low-carbohydrate diets.
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 2816.
Abstract 2819: Serum parietal cell antibodies, gastrin G17 concentration and risk of gastric cancer: A 15 year prospective assessment
Authors: Roth Mark , Qiao You-Lin , Kamangar Farin , Fan Jin-Hu , Diaw Lena , Ren Jian-Song , Taylor Philip R. , Giffen Carol A. , Dawsey Sanford M. , Abnet Christian C. 
Published: February 2011

Abstract
Background: We conducted a prospective nested case-cohort analysis within a high-risk Chinese population to determine if baseline serum PCAs or gastrin was associated with an increased risk of gastric or esophageal cancer during 15 years of follow-up.
Methods: The study included 200 cases of gastric cardia adenocarcinoma (GCA), 200 gastric non-cardia adenocarcinomas (GNCA), 100 esophageal squamous cell carcinomas (ESCC), and a 400 person subcohort of the Linxian General Population Nutritional Intervention Trial cohort. Serum PCA and gastrin G17 concentrations were measured using enzyme-linked immunosorbent assays. Mean sample concentrations were calculated by averaging duplicate optical density measures. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs), using case-cohort models. Models assessed high PCA (Q4 vs Q1) or low gastrin G17 (Q1 vs Q4) and cancer risk. H. pylori status and pepsinogen serology were previously determined (Kamangar et al. Br J. Ca 2007, Ren et al. Gut 2009).
Results: The average time from baseline to cancer diagnosis was 8.1 years. Serum PCA concentrations were non-significantly lower in those who developed GCA than in the subcohort, and were inversely associated with GCA risk. Serum gastrin G17 concentrations were significantly lower in those who developed GNCA than in the subcohort, and were inversely associated with GNCA risk. Neither serum PCA nor gastrin G17 concentration was associated with ESCC risk. These associations were independent of gender, age, smoking, serum pepsinogen I and II concentrations, and H. pylori status. PCA concentration, median (IQR)PwilcoxonPCA Q4 vs Q1PtrendSubcohort (N= 424)0.84 (0.26-5.8)---ESCC (N=95)1.02 (0.32-6.3)0.231.28 (0.65-2.53)&gt;0.5Cardia (N=193)0.59 (0.23-3.2)0.0700.53 (0.30-0.93)0.013Noncardia (N=193)0.85 (0.27-5.4)0.830.76 (0.42-1.35)&gt;0.5 G17 concentration median (IQR)PwilcoxonG17 Q1 vs Q4PtrendSubcohort (N= 424)3.16 (0.78-8.33)-- ESCC (N=95)3.23 (0.57-10.39)0.731.06 (0.55-2.03)0.91Cardia (N=193)3.23 (0.87-6.89)0.681.54 (0.83-2.87)0.30Noncardia (N=193)2.20 (0.30-5.70)0.00203.72 (1.83-7.57)0.00020
Conclusion: High serum parietal cell antibodies were associated with a decreased risk of GCA, and low serum gastrin G17 levels were associated with an increased risk of GNCA in this high-risk population.
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 2819.
Abstract 282: FGF receptor signaling accelerates Wnt-1 mammary tumorigenesis and enhances translation of Wnt/β-catenin target oncogenes
Authors: Pond Adam C. , Herschkowitz Jason I. , Hilsenbeck Susan , Creighton Chad , Lloyd Richard E. , Rosen Jeffrey M. 
Published: February 2011

Abstract
The fibroblast growth factor pathway is known to cooperate with the Wnt/B-catenin pathway in mouse mammary tumorigenesis, and both of these pathways have been implicated in the etiology of human breast cancer. Despite this evidence, little is known about the molecular mechanism contributing to FGF/Wnt pathway cooperation. To investigate the mechanisms involved in this cooperativity, we used genetically engineered mice expressing a drug-inducible model for FGF Receptor signaling (iFGFR) crossed with the well-characterized MMTV-Wnt-1 mouse model. In these bigenic mice, iFGFR1 activation resulted in a dramatic enhancement of mammary tumorigenesis. Tumor microarray analysis did not reveal transcriptional enhancement of Wnt/B-catenin targets, but instead identified a protein translational gene signature that also correlated with elevated FGFR1 and FGFR2 expression in several human breast cancer data sets. Additionally, iFGFR1 activation resulted in enhanced polysome recruitment and a marked increase in protein expression of several different Wnt/B-catenin target oncogenes. Rapid FGFR1-induced ERK activation and phosphorylation of key translation regulators was observed both in vivo in the transgenic mouse model, and in a human breast cancer cell line treated with exogenous FGF. These studies suggest that translational regulation is a key rate-limiting step required for oncogenic cooperativity between the Wnt and FGF pathways. These results not only demonstrate the oncogenic potential of FGFR1 signaling, but also highlight a possible mode of cooperation between FGF and Wnt signaling, involving synergism between two fundamental levels of gene regulation, transcription and translation. FGFRs, provide drugable targets for adjuvant therapy and several known FGFR inhibitors are currently in clinical trials. Additionally, key downstream regulators of translation initiation may also serve as potential therapeutic targets for breast cancers with enhanced FGF signaling.
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 282.
Abstract 2822: Dietary factors and risk of chronic lymphocytic leukemia and small lymphocytic leukemia: A population-based prospective study
Authors: Tsai Huei-Ting , Cross Amanda J. , Graubard Barry I. , Oken Martin , Caporaso Neil E. 
Published: February 2011

Abstract
Background: Chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL) is the most common leukemia in the western hemisphere. Age (advanced), race (Caucasian&gt;Asian) and gender (male) are established risk factors and familial and migration studies strongly support a genetic component. No unequivocal extrinsic environmental risk factors have been reproducibly identified. Using prospective data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, we assessed the effect of diet on CLL/SLL risk.
Methods: Usual dietary intake was assessed in both the intervention and control arms of the trial using a food-frequency questionnaire. We compared distributions of energy-adjusted food intake by CLL/SLL status using Wilcoxon-Rank tests. We categorized dietary intake by quartiles and computed p-values to assess trend effects in ordinal covariates. We used Cox proportional hazards regression, with age as the underlying time metric, to estimate relative risks (RR) and 95% confidence intervals (CIs).
Results: Among 90,414 healthy participants in the PLCO trial, we identified 229 incident cases of CLL/SLL (median age of diagnosis was 71 years; 58% of cases were male) during up to 10 years of follow-up (median: 7 years). Comparing the highest to the lowest quartile of intake, we found no associations for red meat (OR=0.71, 95% CI= 0.47, 1.08), white meat (OR=1.28, 95%.C.I.= 0.87, 1.88),vegetables (OR=1.06, 95% CI= 0.70, 1.61), fruit (OR=0.99, 95% CI= 0.65, 1.51), fiber (OR=1.26, 95% CI= 0.84, 1.90) or fat (OR=0.98, 95% CI= 0.66, 1.46). When we assessed body mass index (BMI), we observed a suggestive increased risk of CLL/SLL, although the effects did not reach statistical significance (OR=1.19, 95% CI= 0.86, 1.64 for pre-obese (25&lt;BMI ≤30); OR=1.20, 95% CI= 0.83, 1.75 for obese (BMI&gt;30), compared to normal weight (18.5&lt;BMI ≤25).
Conclusions: We found no associations between diet and CLL/SLL. The observed tendency for an increase in BMI to be associated with CLL/SLL risk requires further follow-up.
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 2822.