bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2849: A functional promoter variant (rs2075533 C&gt;T) in TNFSF8 involved in apoptosis contributes to decreased risk of lung cancer — a finding from Texas lung cancer genome-wide association study
Authors: Wei Sheng , Niu Jiangong , Zhao Hui , Liu Zhensheng , Wang Li-E , Han Younghun , Amos Christopher I. , Spitz Margaret R. , Wei Qingyi 
Published: February 2011

Abstract
Although genome-wide association studies (GWASs) of lung cancer have identified several significant variants associated with risk of lung cancer, few variants in known biological pathways involved in the etiology of lung cancer have been yet implicated. In this study, we further explored the variants in the extrinsic apoptosis pathway, a fundamental pathway in lung cancer etiology, in 1,154 lung cancer cases and 1,137 cancer-free controls, all being ever-smokers, from the Texas lung cancer (TLC) GWAS (using the Illumina Human370 chip, in which 611 tagSNPs in 41 genes in the apoptosis extrinsic pathway were included. An association analysis using Plink1.06 showed that 10 of these 611 SNPs were associated with risk of lung cancer with a p value &lt;10−2. Among the tagSNPs with the smallest p values, we selected the TNFSF8 gene for further analysis. To search for the tagged functional SNPs, we applied MACH1.0 to impute 52 additional SNPs in the 48-kb region around TNFSF8 based on the genotypes of 10 tagSNPs from the TLC-GWAS database and the genotypes in the same region from the Hapmap database. With further SNP function prediction analyses using SNPinfo and TFSEARCH bioinformatics software, we found that a SNP, −861 C&gt;T (rs2075533), located in the promoter region of TNFSF8 may be a functional SNP. In subsequent functional validation by the luciferase transfection assay, the T allele of this SNP significantly decreased expression of the luciferase reporter constructs by 5-10 fold in all H1299, Hela and HCT116 cell lines tested, compared with the C allele. Our findings implicated a possible novel role of TNFSF8 in the development of lung cancer. Further investigation is warranted to determine whether TNFSF8 rs2075533 alone or in combination with other SNPs contribute to the risk of lung cancer. (Supported by NIH grants R01CA131274, CA055769, CA127219, and R01ES011740)
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 2849.
Abstract 2853: Genetic variation in IGF1, GHR, and IGFBP1 is associated with colorectal cancer
Authors: LeRoy Elizabeth C. , Jacobs Elizabeth T. , Ashbeck Erin L. , Martínez María Elena , Marchand Loic Le , Lance Peter , Duggan David , Thompson Patricia A. 
Published: February 2011

Abstract
Background
The insulin-like growth factor (IGF-1)/growth hormone (GH) pathway has been implicated in the development of colorectal cancer. Circulating IGF-1 increases cell proliferation and inhibits apoptosis. Genetic variation in the IGF pathway genes has been shown to alter circulating IGF-1 concentrations and has been associated with colorectal cancer. This risk may differ by anatomic location.
Methods
We used a principal components approach to evaluate the relationship between genetic variation in six IGF pathway genes (IGF1, IGF2, IGFBP1, IGFBP3, GHR, and GH1) and colorectal cancer in a family-based case-control study from the Colon Cancer Family Registry (CCFR). Cases were recruited from both high-risk clinics and population-based registries. Controls had no previous diagnosis of colorectal cancer and were full biologic siblings of the cases. Clinic-based (cases = 268, controls = 475) and population-based (cases = 1,802, controls = 2,874) data were analyzed separately and all models were adjusted for age and sex.
Results
There was no overall association between genetic variation in the IGF pathway genes and colorectal cancer. However, when the data were analyzed by colorectal cancer anatomic location, GH1 was associated with distal colon cancer (p=0.05) in the population-based families and IGF1 was associated with rectal cancer (p=0.004) in the clinic-based families. Furthermore, when the data were stratified by MSI-status, IGFBP1 was associated with MSI-low/stable tumors (p=0.017) in the clinic-based families.
Conclusion
In this family-based case-control study, genetic variation in IGF1, GHR, and IGFBP1 was associated with colorectal cancer differentially by anatomic location, population source, and tumor type. The clinic-based data represent families with high genetic risk in contrast to the population-based data which represent families of moderate to average genetic risk. These results replicate prior case-only analyses that suggest IGF1 is a modifier of colorectal cancer risk in high-risk families. Single SNP analyses and exploration of SNP x SNP interactions may further elucidate the significance of IGF pathway genes on colorectal cancer risk.
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 2853.
Abstract 2857: SULT1A1 gene copy number variations and functional polymorphism in relation to breast cancer risk
Authors: Li Guoliang , Ye Chuanzhong , Shu Xiao-Ou , Wen Wanqing , Lu Wei , Zheng Wei , Cai Qiuyin 
Published: February 2011

Abstract
Sulfotransferase (SULT) 1A1 enzyme plays an important role in the detoxification of environmental and dietary procarcinogens as well as the regulation of a number of steroid hormones, including estrogens. SULT1A1 gene is located in the short arm of chromosome 16, which has been shown to contain many repetitive sequences and to be highly duplicated. It has been suggested that SULT1A1 gene displays variations in copy number. In our previous study, a common functional polymorphism rs9282861 (213Arg&gt;His) in SULT1A1 was associated with an elevated risk of breast cancer in postmenopausal Caucasian women. In this study, we evaluated copy number variations and functional polymorphism rs9282861 of SULT1A1 gene in relation to breast cancer risk. Included in the study were 1,989 breast cancer cases and 1,918 controls from the Shanghai Breast Cancer Study II, a population-based, case-control study conducted among Chinese women. SULT1A1 gene copy number was determined by real-time PCR assays and genotyping was conducted using TaqMan assays. One to five copies of the SULT1A1 were observed in our population. Approximately 22.6% of these women were found to have more than 2-copy of the SULT1A1 gene and 1.7% of these women were found to have 1-copy of the gene. No woman was found to have null copy of SULT1A1 gene. No overall association of the SULT1A1 gene copy number variations with breast cancer risk was observed. We found that the A allele (213His) of rs9282861 was associated with a reduced risk of breast cancer risk. Women carrying GA/AA genotypes had an OR of 0.81 (95%CI=0.68-0.97) compared to women carrying GG genotype. The inverse association was constraint in pre-menopausal women with OR of 0.68 (95%CI=0.53-0.87) for women carrying GA/AA genotypes compared to those carrying GG genotype. There is no interaction between SULT1A1 gene copy number variations and polymorphism 213Arg&gt;His in relation to breast cancer risk. Our data suggest that functional 213Arg&gt;His polymorphism of SULT1A1 gene, not SULT1A1 gene copy number change, may play a role in the etiology of 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 2857.
Abstract 2858: Relation of androgen receptor polymorphisms and prostate cancer risk by level of sex steroid hormones
Authors: Sakoda Lori C. , Weiss Noel S. , Barnett Matt , Goodman Gary E. , Chen Chu 
Published: February 2011

Abstract
Given that androgens exert their effects on target tissues through androgen receptor (AR) binding, polymorphic variation in the AR gene may influence prostate cancer development. Studies examining the AR CAG and GGC repeat polymorphisms in relation to prostate cancer risk, however, have yielded conflicting results. In a case-control study of prostate cancer nested in the β-carotene and Retinol Efficacy Trial, we previously found suggestive evidence of reduced risk in men with a small number of AR CAG [&lt;22 versus ≥22: odds ratio (OR), 0.89; 95% confidence interval (CI): 0.65-1.23] or GGC [≤17 versus &gt;17: OR, 0.80; 95% CI: 0.57-1.12] repeats. The possibility that these associations are more pronounced in certain subgroups of men, with respect to level of circulating sex steroid hormones, has not yet been examined. In the same population of 300 cases and 300 controls, we now explore whether prostate cancer risk associated with CAG or GGC repeat length may differ by levels of serum testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, 3α-androstanediol glucuronide, and sex hormone binding globulin concentrations. To cases diagnosed from 1987-1998 who had blood drawn from 0.5 to 8.5 (mean: 3) years prior, controls who were free of prostate and lung cancer were matched on the basis of age, race, study center, time of blood draw, time from enrollment to blood draw, and year of randomization. We found no trend in prostate cancer risk associated with short (≤17) GGC repeat length across thirds of the distribution of the hormones, except for estradiol. For men in the lowest, middle, and highest third of total estradiol, the ORs (95% CIs) were 1.16 (0.65-2.10), 0.87 (0.50-1.72), and 0.50 (0.27-0.92), respectively (p-interaction=0.14). A similar, but weaker association pattern was noted across thirds of free estradiol. No clear differences in the relation of CAG repeat length and prostate cancer risk across levels of each hormone were found. Since the observed positive results may be due to chance, further investigation is needed to determine whether AR GGC repeat length and circulating sex steroid hormone levels interact to alter prostate cancer risk.
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 2858.
Abstract 286: Expression and role of fibroblast growth factor receptor2 IIIc in human uterine cervical intraepithelial neoplasia (CIN) and invasive cervical cancer
Authors: Kawase Rieko , Ishiwata Toshiyuki , Matsuda Yoko , Onda Munehiko , Teduka Kiyoshi , Kawahara Kiyoko , Takeshita Toshiyuki , Naito Zenya 
Published: February 2011

Abstract
Fibroblast growth factor receptors (FGFR) FGFR1 through FGFR3 possess IIIb and IIIc isoforms as the result of alternative splicing of the immunoglobulin-like domain. The IIIb isoforms are mainly expressed in normal epithelial cells, and IIIc isoforms are expressed in mesenchymal cells. Single nucleotide polymorphisms (SNPs) of the FGFR2 gene are associated with endometrial cancer, and missense mutations or copy number gains of the FGFR2 gene occur in breast cancer. In uterine cervical cancer, FGFR2 IIIb, also known as keratinocyte growth factor receptor (KGFR), was reported to be highly expressed in squamous cell carcinoma (SCC), which accounts for 90% of all cervical cancer patients. However, there has been no report on the expression and roles of FGFR2 IIIc in cervical cancer. In the present study, we determined the expression and roles of FGFR2 IIIc in CIN and cervical SCC. In noncancerous cervical tissues, FGFR2 IIIc immunoreactivity was either not present or very faintly localized in squamous epithelial cells. In CINs 1 and 2, FGFR2 IIIc was localized at the basal to lower two-thirds of squamous epithelium, whereas FGFR2 IIIc was strongly expressed in most of the squamous epithelium, except for the superficial layer in CIN 3. FGFR2 IIIc protein was detected in keratinizing and non-keratinizing types of SCC in all cervical cancer patients examined (8 and 21 cases, respectively). In situ hybridization (ISH) analysis using an FGFR2 IIIc-specific antisense RNA probe showed that the expression patterns of FGFR2 IIIc mRNA are similar to those of FGFR2 IIIc protein in noncancerous and CIN tissues. In addition, FGFR2 IIIc mRNA was strongly expressed in the invasive fronts of cancer cell nests in cancer tissues. Moreover, full-length FGFR2 IIIc cDNA, subcloned to pIRES2-EGFP vector, was stably transfected into CaSki cells, which are derived from a well-differentiated type of SCC. The growth rates of the FGFR2 IIIc-transfected CaSki cells were higher than those of mock cells in vitro. Cell migration assays did not show any differences between FGFR2 IIIc-transfected CaSki cells and mock cells. To assess the effect of FGFR2 IIIc expression on tumorigenicity, the CaSki cells were injected into nude mice. The FGFR2 IIIc-transfected CaSki cells tended to form larger subcutaneous tumors than mock cells in nude mice. These findings suggest that FGFR2 IIIc plays important roles in the carcinogenesis and proliferation of cervical cancer cells. FGFR2 IIIc is considered to be a novel therapeutic target for inhibiting the growth of CIN and cervical 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 286.
Abstract 2874: A γ-tocopherol-rich mixture of tocopherols inhibits chemically induced lung tumorigenesis in A/J mice and xenograft tumor growth
Authors: Lu Gang , Xiao Hang , Li GuangXun , Picinich Sonia C. , Chen Yu-Kuo , Liu Anna , Li Mao-Jung , Loy Shea , Yang Chung S. 
Published: February 2011

Abstract
The present study investigated the effects of a preparation of a γ-tocopherol (γ-T)-rich mixture of tocopherols (γ-TmT) and its combination with EGCG on chemically induced lung tumorigenesis in female A/J mice and the growth of H1299 human lung cancer cell xenograft tumors. In the A/J mouse model, the lung tumors were induced by either 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; i.p. injections with 100 and 75 mg/kg on Week 1 and 2, respectively) or NNK plus benzo[a]pyrene (B[a]P) (8 weekly gavages of 2 μmol each from Week 1 to 8). The NNK plus B[a]P treatment induced 21 tumors per lung on Week 19; dietary 0.3% γ-TmT treatment during the entire experimental period significantly lowered tumor multiplicity, tumor volume and tumor burden (by 30%, 51% and 60%, respectively; P&lt;0.05). For three groups of mice treated with NNK alone, the γ-TmT diet was given during the initiation stage (Week 0 to 3), the post-initiation stage (Week 3 to 19), or the entire experimental period, and tumor multiplicity was reduced by 17.8%, 19.7%, or 29.3%, respectively (P&lt;0.05). γ-TmT treatment during the tumor initiation stage or throughout the entire period of the experiment also significantly reduced tumor burden (by 36% or 43%, respectively). In the xenograft tumor model of human lung cancer H1299 cells in NCr-nu/nu mice, 0.3% dietary γ-TmT treatment significantly reduced tumor volume and tumor weight by 56% and 47%, respectively (P&lt;0.05). In both the carcinogenesis and tumor growth models, the inhibitory action of γ-TmT was associated with enhanced apoptosis and lowered levels of 8-hydroxydeoxyguanine, γ-H2AX and nitrotyrosine in the tumors of the γ-TmT-treated mice. These results demonstrate the inhibitory effect of γ-TmT against lung tumorigenesis and the growth of xenograft tumors of human lung cancer cells. The inhibitory activity may be due mainly to the actions of δ-T and γ-T. We further studied the tumor inhibitory effects of a combination of γ-TmT and EGCG in the above mentioned NNK-induced lung tumorigenesis model. The treatment with γ-TmT (0.3%), EGCG (0.4%), and the combination at half doses (0.15% γ-TmT plus 0.2% EGCG) all significantly reduced the tumor multiplicity in the NNK-induced model. In this experiment, we observed by immunohistochemistry that dietary γ-TmT treatment increased the glutathione peroxidase and superoxide dismutase levels, but EGCG treatment had no effect on these two enzymes. The levels of catalase, heme oxigenase-1 and Nrf2 were not changed by either agent (Supported by NIH grants CA122474 and CA 133021).
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 2874.
Abstract 2877: TRAMP-injected mice fed a no-carbohydrate ketogenic diet demonstrate prolonged survival and decreased tumor volumes compared to mice fed western or low-fat diets
Authors: Whitley Brian M. , Masko Elizabeth M. , Thomas Jean A. , Kim Howard S. , Poulton Susan A. , Phillips Tameika E. , Freedland Stephen J. 
Published: February 2011

Abstract
Introduction and Objective: In multiple previous studies, we have shown that mice injected with subcutaneous prostate cancer cells (LNCaP or LAPC-4) and fed a no-carbohydrate ketogenic diet (NCKD, 84% fat, 0% carbohydrate, 16% protein) have significantly decreased tumor volume and significantly prolonged survival, compared to mice fed a western diet (WD, 40% fat, 44% carbohydrate, 16% protein). All previous studies utilized a human prostate cancer cell line, requiring the use of immunodeficient mice. We sought to replicate these previous studies to determine whether diet affected tumor progression and survival in an immunocompetent model.
Methods: In this treatment model, 75 male C57bl/6 mice were initially fed WD ad libitum for a period of 14 days. After this 14 day period, all mice were injected subcutaneously with 2.5×105 TRAMP cells and randomized to one of three diets: WD, NCKD, or low-fat diet (LF, 12% fat, 72% carbohydrate, 16% protein). Mice receiving LF diet were fed ad libitum, and served as the reference group in paired-feeding protocols for mice receiving WD and NCKD. Tumor volumes were assessed twice weekly, and mice were sacrificed when tumor volumes reached 1000mm3. Survival was calculated using a Log-rank test and tumor volumes were compared among dietary groups using Kruskal-Wallis test for significance.
Results: Mice fed a NCKD demonstrated a trend towards decreased tumor volumes compared to mice fed WD and LF. Median tumor volume at study day 66 for mice fed WD, LF, and NCKD were 1091.2 mm3, 1082.9 mm3, and 661.5mm3 respectively. While the tumor volumes were smaller in mice fed NCKD versus LF or WD, these differences did not reach statistical significance (WD vs. NCKD, p=0.06; LF vs. NCKD, p=0.12). There was no significant difference between tumor volumes among mice fed WD compared to LF (p=0.95). Additionally, a trend towards improved survival was seen in mice fed NCKD vs. WD (p=0.09).
Conclusion: This study in an immunocompetent xenograft model supports the findings of multiple previous studies. Mice fed a NCKD demonstrated a trend towards prolonged survival and decreased tumor volume compared to mice fed WD.
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 2877.
Abstract 2878: Dietary stearate inhibits tumor development and tumor burden in the N-nitroso-N-methylurea (NMU) rat breast cancer carcinogen model
Authors: Hardy Robert W. , Toline Eric , Evans Lynda M. , Desmond Renee , Ibrahim-Hashim Arig , Siegal Gene P. 
Published: February 2011

Abstract
The goal of the present study was to test the effectiveness of dietary stearate at inhibiting breast cancer development in a carcinogen induced breast cancer model. Three diets were used; a 17% stearate diet, the key being that highly purified stearate was added directly to the diet, a linoleate diet (SF) containing 17% safflower oil as the source of linoleate and a low fat control diet (LF) with a reduced amount of fat (5%) from corn oil. All three diets had adequate essential fatty acids. These 3 diets were initiated 1 week prior to the rats receiving NMU and followed out 100 days. There was no difference in the weight of the rats among groups throughout the study. Approximately 40% fewer animals on the stearate and safflower diets developed palpable tumors compared to the LF (n=30-35 animals/diet; p&lt;0.05). No difference was observed among the three diets as to the time for first tumor appearance. Stearate decreased the average number of tumors per rat compared to the LF (n=30-35 animals per diet; p&lt;0.05) and had less tumors per rat than the SF although this was not statistically significant. Stearate also significantly reduced tumor burden as defined by tumor weight by ∼50% compared to LF and SF (p&lt;0.001) and large tumors compared to the LF (∼47% reduction in tumors over 0.25 g, p= 0.02). In those rats that did develop tumors, the stearate diet group had a similar number of adenocarcinomas compared to other diets; however the stearate and SF groups had lower numbers of DCIS/microinvasive disease as compared to the LF. The dietary groups tended to have similar numbers of the other precursor lesions classified although the dietary stearate group had the least number of “tubular adenomas”. Dietary stearate may be useful as an alternative/complementary therapy or preventative agent against 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 2878.