bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 894: Genetic variations in the angiogenesis pathway modulate clinical outcomes of bladder cancer
Authors: Chen Meng , Lerner Seth , McConkey David , Gu Jian , Kamat Ashish , Grossman H. Barton , Dinney Colin P. , Wu Xifeng 
Published: February 2011

Abstract
Bladder cancer is the fourth most common cancer in men in the United States. There is compelling evidence suggesting that a patient's genetic background contributes to bladder cancer clinical outcome. Angiogenesis is an essential process required for tumor development, growth, and metastasis. We hypothesized that genetic variations in the angiogenesis pathway may affect the overall survival of bladder cancer patients. We conducted a follow-up study of 397 non-muscle invasive and 320 muscle-invasive bladder cancer patients to systematically evaluate 458 single nucleotide polymorphisms (SNPs) in 24 angiogenesis pathway genes as predicators of prognosis and BCG response. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by multivariate Cox proportional hazard regression adjusting for age, gender, stage, grade, and treatment regimen. In non-muscle invasive bladder cancer patients, no significant SNPs were identified after correction for multiple comparisons. When stratified by BCG treatment, variant KIT rs11735550 was significantly associated with recurrence in patients who did not receive BCG treatment (HR=2.84, 95%CI: 1.67-4.83). In muscle-invasive bladder cancer patients, variant FLT4 rs11750142, rs2447737, rs13168072, and rs11739750 genotypes, and wild-type rs11957360 were significantly associated with increased risk of dying. These SNPs are not in linkage disequilibrium suggesting that each one independently modulates survival. In addition, a significant gene dosage effect was observed for increased risk with increasing number of unfavorable genotypes (P for trend&lt;0.001). Compared to the low-risk group (0-1 unfavorable genotypes), median-risk group (2-3 unfavorable genotypes) and high-risk group (4-5 unfavorable genotypes) showed 1.34- (95%CI: 0.86-2.11) and 2.60-fold (95%CI: 1.66-4.09) increased risk of dying, respectively. In Kaplan-Meier estimates, the low-, median-, and high-risk groups had significantly different median survival time (MST) of 81.9, 67.9, and 31.3 months, respectively (logrank P &lt;0.01). These results support the hypothesis that genetic variations in the angiogenesis pathway modulate clinical outcomes for bladder cancer patients. These findings warrant further replication in independent populations, and could be useful in disease management and the development of targeted therapies for bladder 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 894.
Abstract 895: NFκB and IκBKB polymorphisms and colorectal cancer survival in the Seattle Colon Cancer Family Registry
Authors: Coghill Anna E. , Newcomb Polly A. , Poole Elizabeth M. , Duggan Dave , Makar Karen W. , Ulrich Cornelia M. 
Published: February 2011

Abstract
Introduction: IκBKB and NFκB are regulatory enzymes that interact with the prostaglandin synthesis pathway, which plays a key role in inflammation and colorectal carcinogenesis. Transcriptional targets of the nuclear factor NFκB have been linked to cellular proliferation, angiogenesis, and metastasis. IκBKB binds NFκB within the cytoplasm and can prevent its nuclear localization. The role of variability in these genes in relation to colorectal cancer (CRC) survival has not been investigated; we therefore examined polymorphisms in both IκBKB and NFκB in relation to CRC survival.
Methods: CRC cases were ascertained from 1997-2002 from the Seattle Colon Cancer Family Registry and were matched through linkages to the National Death Index records to obtain date and cause of death. A subgroup of CRC cases was genotyped for selected tagSNPs (9 in IκBKB; 44 in NFκB), including non-synonymous candidate polymorphisms (IκBKB: rs17875749, rs2272736; NFκB: rs4648072, rs4648099). Cox proportional hazards regression models were used to estimate hazard ratios investigating the relationship between polymorphisms in IκBKB and NFκB and CRC-specific mortality.
Results: We observed statistically significant inverse associations between four SNPs in IκBKB (rs11986055, rs2272733, rs6474387, and rs9694958) and the risk of CRC mortality after diagnosis. The observed survival benefit ranged from 86% reduced CRC mortality risk for rs11986055 (HR AA vs. AC or CC: 0.14, 95% CI 0.02-1.03) to 59% reduced CRC mortality risk for rs2272733 (HR GG vs. GA or AA: 0.41, 95% CI 0.20-0.82). The functional significance of these SNPs is unknown; none of these SNPs were in high linkage disequilibrium, with all r2 values &lt; 0.7. No SNPs investigated in NFκB were significantly associated with colorectal cancer survival.
Conclusion: These data suggest that certain polymorphisms in IκBKB may be associated with mortality from colorectal cancer after diagnosis.Associations between IκBKB polymorphisms and CRC survival Hazard Ratio95% CIp-valueAliveDeaadrs11986055 A&gt;C AA1.00Ref. 20279AC or CC0.140.02-1.030.05241rs2272733 G&gt;A GG1.00Ref. 17571GA or AA0.410.20-0.820.01519rs6474387 C&gt;T CC1.00Ref. 18875CT or TT0.400.16-1.000.05365rs9694958 A&gt;G AA1.00Ref. 18874AG or GG0.370.16-0.860.02386All models reported above adjusted for age, sex, and stage of disease at diagnosis
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 895.
Abstract 896: Pre-diagnostic blood fatty acid levels and prostate cancer mortality
Authors: Chavarro Jorge E. , Stampfer Meir J. , Campos Hannia , Sesso Howard D. , Ma Jing 
Published: February 2011

Abstract
Purpose: Fatty acid metabolism, particularly de novo lipogenesis, may be an important determinant of prostate cancer progression and mortality. However, epidemiologic data regarding the role of circulating fatty acids, as biomarkers of fatty acid intake and metabolism, on prostate cancer progression and mortality is scarce.
Methods: We conducted a prospective cohort study among 582 Physicans’ Health Study participants who provided a blood sample in 1982 and who were later diagnosed with prostate cancer, between 1982 and 2006. Blood samples were kept frozen until they were assayed. Men were followed from the date of prostate cancer diagnosis until death or the end of follow-up (March 31, 2009). Blood levels of major types of fatty acids were measured using gas chromatography and expressed as percentage of total fatty acids. Men were categorized according to quintiles of blood fatty acid levels. Proportional hazards regression was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of prostate cancer specific mortality in a given quintile of fatty acid level in relation to the lowest quintile.
Results: During 7,414 person-years of follow-up, 94 men died of prostate cancer. The median time between diagnosis and prostate cancer death was 14 years. The median time between blood draw and prostate cancer diagnosis was 9.5 years. Blood levels of all the mono-unsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids examined were unrelated to prostate cancer mortality. However, compared to men in the lowest quintile, the RRs (95% CIs) of prostate cancer mortality for men in increasing quintiles of blood stearic acid (18:0) levels were 1.90 (0.81-4.50), 3.61 (1.55-8.42), 2.29 (0.96-5.43) and 4.96 (2.10-11.7) (P, trend &lt;0.001) after adjusting for age at diagnosis, race, body mass index, smoking status, clinical stage and tumor grade at diagnosis, and time between blood draw and prostate cancer diagnosis. Blood levels of the remaining saturated fatty acids examined were unrelated to prostate cancer mortality.
Conclusions: Pre-diagnostic blood levels of stearic acid, a saturated fatty acid, are positively related to prostate cancer mortality. Since blood stearic acid levels are usually unrelated to diet, these data suggest that differences in fatty acid metabolism might be responsible for this association. It remains to be determined whether this finding is due to between-person differences in the activity of de novo lipogenesis enzymes or other metabolic factors that result in higher blood levels of stearic acid.
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 896.
Abstract 902: Associations between methylenetetrahydrofolate reductase polymorphisms and survival in patients with colorectal cancer treated with 5-FU-based adjuvant chemotherapy: A thirteen years follow-up study
Authors: Yeh Chih-Ching , Chang Shih-Ni , Sung Fung-Chang , Hsieh Ling-Ling , Tang Reiping 
Published: February 2011

Abstract
PURPOSE
The study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and overall survival (OS) of patients with colorectal cancer (CRC) treated with 5-Fluorouracil (5-FU)-based chemotherapy.
PATIENTS AND METHODS
We genotyped MTHFR polymorphisms (C677T and A1298C) for 530 CRC patients treated with 5-FU-based chemotherapy after receiving surgery between 1995 and 1999. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. The association between MTHFR genotypes and survival was analyzed using Cox proportional hazard models and haplotype analysis.
RESULTS
After 13 years follow-up, the median survival year was 4.77 (95% CI, 4.0 to 6.1). The OS was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR = 0.77; 95% CI, 0.61 to 0.98). Although no association was found between the MTHFR A1298C polymorphism and OS in CRC, this polymorphism showed significant differences in OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with the AC+CC genotypes than those with the AA genotype (HR = 1.94; 95% CI, 1.34 to 2.80). In haplotype analysis, better survival was related to colon patients carrying the MTHFR 677T-1298A haplotype, but worse survival was linked to rectal cancer carrying the MTHFR 677C-1298C haplotype.
CONCLUSION
To our knowledge, our study is the largest to investigate the relationship between MTHFR polymorphisms and OR in CRC patients in a Chinese population. Our findings suggest that MTHFR genotypes provide prognostic information in CRC patients treated with 5-FU-based chemotherapy.
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 902.
Abstract 903: Long-term survivors in advanced non-small cell lung cancer
Authors: Fujiuchi Satoru , Fujita Yuka , Nishigaki Yutaka , Nakanishi Kyoko , Yamamoto Yasushi , Takeda Akinori , Yamazaki Yasuhiro , Fujikane Toshiaki 
Published: February 2011

Abstract
Background:
It is known that chemotherapy for advanced non small-cell lung cancer (NSCLC) improves the prognosis, however, with regard to 2-year survival rate of inoperable stage III/IV patients is up to 20%. The contribution of chemotherapies for survival is not fully satisfied yet.
Purpose:
The aim of this study is to evaluate the rate of long-term survival of more than 2 years in patients with advanced NSCLC and elucidate clinical factors that affect long-term survival in those patients.
Methods:
We retrospectively reviewed 103 patients with inoperable, stage III/IV NSCLC treated with chemotherapy from January 2005 to December 2006 at Dohoku National Hospital. These included 69 adenocarcinomas, 22 squamous cell carcinomas, 9 large cell carcinomas and 3 others. These patients were divided into two groups: those who survived more than 2 years (long-term survivors; LTS) and the others (non long-term survivors; non LTS). We analyzed the prognostic factors that affect the survival in this setting. The difference of characteristics between two groups was tested with the Mann-Whitney U test, the chi-square test or Fisher's exact test. Survival curves were calculated according to Kaplan-Meier method. The correlations of variables with survival were analyzed by multivariate analysis using a Cox proportional hazards model.
Results:
There were 27 (26.2%) patients who survived more than 2 years (LTS). All of them had performance status (PS) 0 or 1. These LTS included 13 females, 11 non-smoker, 21 adenocarcinomas and 17 stage IV disease. LTS showed significant correlation with gender, smoking status, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), and response of gefitinib (SD or better) (p=0.0008, p=0.0457, p=0.0317, p=0.0004 and p=0.0026, respectively). Patients who respond to initial chemotherapy (SD or better) as well as gefitinib showed favorable course. Univariate analyses showed that PS 0-1, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), response of gefitinib (SD or better) were significantly associated with better prognosis (p=0.0036, p=0.0203, p&lt;0.0001 and p=0.0090, respectively). Multivariate analyses showed absence of bone metastases, response of 1st-line chemotherapy (SD or better), response of gefitinib (SD or better) were significantly associated with good prognosis (p=0.0031, p&lt;0.0001 and p=0.0028, respectively). Conclusions: Absence of bone metastases, response of 1st-line chemotherapy and response of gefitinib are the significant factors to predict better prognosis in patients with advanced 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 903.
Abstract 905: Associations with breast cancer survival replicated for three SNPs: A report from the Shanghai Breast Cancer Survival Study and Shanghai Breast Cancer Study
Authors: Beeghly-Fadiel Alicia C. , Long Jirong , Gao Yutang , Zheng Ying , Cai Qiuyin , Gu Kai , Chen Zhi , Lu Wei , Zheng Wei , Shu Xiao Ou 
Published: February 2011

Abstract
We have previously reported associations between nine single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (SBCS, Stage I). We evaluated these SNPs in association with overall survival (OS) and disease free-survival (DFS) among participants of the Shanghai Breast Cancer Survival Study (SBCSS) and participants of the second phase of SBCS (Stage 2). The mean follow-up time of the 1,115 Stage 1 participants was 6.5 years; the mean follow-up time of the 5,381 Stage 2 participants was 4.2 years. Models of effect and subgroup analyses were conducted based on published results from Stage 1. A missense SNP in exon 1 of TGFβ1 (rs1800470) was associated with improved overall survival in a recessive fashion (p-value = 0.028). Minor allele homozygotes (TT) fared slightly better than major allele carriers (CT and CC) (OS hazard ratio (HR): 0.8, 95% confidence interval (CI): 0.6-1.0); this effect was slightly attenuated after adjustment for known prognostic factors including age, disease stage, tumor estrogen and progesterone receptor status, and disease treatment (p-value = 0.052). A SNP downstream of the MMP7 gene (rs11225297), in high linkage disequilibrium with a nearby functional SNP, was associated with improved overall survival in an additive manner (p-value = 0.013). Compared to major allele homozygotes (AA), heterozygotes (AT) fared moderately better (OS HR: 0.8, 95% CI: 0.7-1.0), while homozygotes (TT) fared much better (OS HR: 0.5, 95% CI: 0.3-1.0); this affect was strengthened by adjusting for known covariates (p-value = 0.002). Finally, a functional promoter SNP in MMP8 (rs11225395) was found to be associated with better prognosis among early stage patients (TNM less than 3) in a dominant manner (p-value = 0.007). Early stage minor allele carriers (CT and TT) had better survival (DFS and OS HRs: 0.7, 95% CI: 0.5-0.9); these effects were unaltered by adjusting for covariates (p-values = 0.012). In summary, we were able to replicate associations with breast cancer survival for three of nine previously reported SNPs. These findings suggest that genetic polymorphism in genes governing the tumor microenvironment may play an important role in breast cancer prognosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 905.
Abstract 908: Genetic variants in one-carbon metabolism related genes contribute to NSCLC prognosis in a Chinese population
Authors: Guangfu Jin , Hu Zhibin , Shen Hongbing 
Published: February 2011

Abstract
One-carbon metabolism plays a critical role in both DNA methylation and DNA synthesis. Genetic variants of genes coding enzymes involved in one-carbon metabolism may result in aberrant methylation and/or DNA synthesis inhibition, and ultimately modulate the initiation and progression of tumors. In the present study, we hypothesized that polymorphisms in one-carbon metabolism related genes may contribute to the prognosis of non-small cell lung cancer (NSCLC). To test this hypothesis, we screened 57 potentially functional single nucleotide polymorphisms (SNPs) from 11 candidate genes involved in one-carbon metabolism and genotyped them in a cohort of 568 NSCLC patients by using Illumina Golden Gate platform. Kaplan-Meier method with log-rank test and Cox proportional hazard models were used for the survival analyses. We found that variant alleles were significantly associated with favorable survivals of NSCLC for MTR rs3768160 A&gt;G (allelic hazards ratio (HR) = 0.78, 95% confidence interval (CI): 0.62-0.98), MTRR rs2966952 G&gt;A (allelic HR = 0.84, 95%CI: 0.71-0.99) and DHFR rs1650697 G&gt;A (allelic HR = 0.83, 95%CI: 0.70-0.99), and with unfavorable prognosis for MTHFD1 rs1950902 G&gt;A with borderline significance (allelic HR = 1.18, 95%CI: 0.99-1.40). In addition, the combined genotypes of above four SNPs showed a locus-dosage effect on NSCLC survival (P for trend = 6.9 × 10−5). In the final multivariate Cox regression model, combined genotypes were identified as an independent prognostic factor for NSCLC with adjusted HR of 0.78 (95% CI: 0.66-0.92; P = 3.7 × 10−3). These findings indicate that genetic variants in one-carbon metabolism pathway may be candidate biomarkers for NSCLC prognosis.
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 908.
Abstract 911: Genetic variations in the one-carbon transfer pathway and aberrant DNA methylation in prostate cancer
Authors: Watanabe Masatoshi , Hirokawa Yoshifumi , Suzuki Hiroyoshi , Ichikawa Tomohiko , Katoh Takahiko , Sugimura Yoshiki , Shiraishi Taizo 
Published: February 2011

Abstract
Many molecular studies have indicated that genetic and epigenetic alterations are important for carcinogenesis in the prostate. Alterations in the one-carbon metabolism pathway can influence DNA synthesis and DNA methylation. Polymorphisms in the genes for the methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), serine hydroxymethyltransferase (SHMT) have been reported to be associated with some forms of malignancies. In a case-control study of 300 cases and 240 controls, we investigated whether four common polymorphisms in the MTHFR (C677T and A1298T), MTR (A2756G), SHMT1 (C1420T), MTRR (A66G), reduced folate carrier (RFC-1, A80G), and methylenetetrahydrofolate-dehydrogenase (MTHFD, G1958A) may have a role in altering prostate cancer susceptibility. The genotype was mainly determined by the PCR-RFLP method. The MTHFR 677TT genotype was associated with a significant decrease in the risk with an adjusted odds ratio of 0.57 (95% confidence interval: 0.34-0.94). The RFC-1 80GG genotype was associated with a significant increase in the risk with an adjusted odds ratio of 1.75 (95% confidence interval: 1.07-2.87). However, the MTHFR A1298C, MTR A2756G and SHMT1 C1420T, MTRR A66G and MTHFD G1958A were not associated with prostate cancer risk. We also analyzed CpG island hypermethylation in five genes (GSTP1, RARβ2, AR, DAPK, TIMP-3 and hMLH1) and its association with these polymorphisms in 100 prostate cancers. However no significant association was detected. These findings suggest that polymorphism of the MTHFR may be involved in carcinogenesis of the prostate.
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 911.