bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gilbert's Syndrome and Irinotecan Toxicity: Combination with UDP-Glucuronosyltransferase 1A7 Variants Increases Risk
Authors: Lankisch Tim O. , Schulz Christoph , Zwingers Thomas , Erichsen Thomas J. , Manns Michael P. , Heinemann Volker , Strassburg Christian P. 
Published: March 2008

AbstractBackground: Gilbert's syndrome is characterized by a functional promoter single nucleotide polymorphism (SNP) of the UDP-glucuronosyltransferase (UGT) 1A1 gene and represents a pharmacogenetic risk factor for irinotecan toxicity, but study data remain controversial. The active CPT-11 metabolite 7-ethyl-10-hydroxycamptothecin is detoxified by several UGT1A proteins, which include UGT1A7 with a high specific activity that may contribute to the risk of irinotecan toxicity in Gilbert's syndrome patients.Methods: Genotyping of the UGT1A1*28, UGT1A7 N129K/R131K, and UGT1A7-57T/G variants was done in 105 irinotecan-treated patients with metastatic colorectal cancer; adverse events were documented during all 297 treatment cycles and analyzed by Cochran-Mantel-Haenszel, Mann-Whitney, and χ2 tests.Results: The presence of UGT1A7 but not UGT1A1 variants was associated with at least one adverse event. In patients combining all three variants, thrombocytopenia and leukopenia were significantly more frequent. The overall incidence of adverse events was significantly higher (P = 0.0035) in carriers of the UGT1A risk alleles, who also had significantly higher rate of dose reductions.Conclusions: Irinotecan toxicity is more likely in patients with Gilbert's syndrome carrying the UGT1A1*28 allele combined with reduced function UGT1A7 N129K/R131K and UGT1A7-57T/G SNP. Based on the ability of UGT1A7 to metabolize and eliminate the active irinotecan metabolite 7-ethyl-10-hydroxycamptothecin, the UGT1A1/UGT1A7 SNP combination haplotype appears to be a superior risk predictor than Gilbert's syndrome alone. (Cancer Epidemiol Biomarkers Prev 2008;17(3):695–701)
Association of Genetic Variants at 8q24 with Breast Cancer Risk
Authors: Fletcher Olivia , Johnson Nichola , Gibson Lorna , Coupland Ben , Fraser Agnes , Leonard Angela , dos Santos Silva Isabel , Ashworth Alan , Houlston Richard , Peto Julian 
Published: March 2008

Abstract
Recent whole genome association studies of prostate, breast, and colorectal cancer have identified susceptibility loci on 8q24. We genotyped three variants associated with prostate cancer (rs10090154, rs13254738, and rs7000448), one associated with both prostate and colorectal cancer (rs6983267), and one associated with breast cancer (rs13281615) in a series of 1,499 breast cancer cases and 1,390 controls. 1,267 (85%) of the cases had two primary breast cancers. Our analysis provides further evidence of the relationship between rs13281615 and risk of breast cancer, with heterozygote odds ratio (OR) 1.30 95% confidence interval (CI) 1.09-1.54 and homozygote OR 1.52 (95% CI, 1.22-1.89; Ptrend = 0.00003), and confirms the prediction that the risk is substantially higher in this genetically enriched series (OR per allele, 1.24; 95% CI, 1.12-1.38) than in a large series of mainly unselected cases (reported OR per allele, 1.08; 95% CI, 1.05-1.11). We observed a protective effect of rs13254738 for breast cancer (allelic OR, 0.88; 95% CI, 0.78-0.98; P = 0.02), which is supported by the Cancer Genetic Markers of Susceptibility data (pooled allelic OR, 0.88; 95% CI, 0.81-0.96; P = 0.003). None of the other three single nucleotide polymorphisms, two associated with prostate (rs10090154 and rs7000448) and one with both prostate and colorectal cancers (rs6583267), was associated with breast cancer risk in our study. This evidence of a protective effect for breast cancer of one variant (rs13254738) that has been associated previously with a 1.25-fold increased risk of prostate cancer, with no effect for the two other variants, indicates that the effects of the risk alleles clustered at 8q24 are cancer site specific. (Cancer Epidemiol Biomarkers Prev 2008;17(3):702–5)
Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Gene Polymorphisms and Risk of Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma
Authors: Ferguson Heather R. , Wild Christopher P. , Anderson Lesley A. , Murphy Seamus J. , Johnston Brian T. , Murray Liam J. , Watson R.G. Peter , McGuigan Jim , Reynolds John V. , Hardie Laura J. 
Published: March 2008

Abstract
The incidence of esophageal adenocarcinoma has increased in recent years, and Barrett's esophagus is a recognized risk factor. Gastroesophageal reflux of acid and/or bile is linked to these conditions and to reflux esophagitis. Inflammatory disorders can lead to carcinogenesis through activation of “prosurvival genes,” including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Increased expression of these enzymes has been found in esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Polymorphic variants in COX-2 and iNOS genes may be modifiers of risk of these conditions. In a population-based case-control study, we examined associations of the COX-2 8473 T&gt;C and iNOS Ser608 Leu (C&gt;T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), and reflux esophagitis (n = 230) and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. The presence of at least one COX-2 8473 C allele was associated with a significantly increased risk of esophageal adenocarcinoma (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.40). There was no significant association between this polymorphism and risk of Barrett's esophagus or reflux esophagitis or between the iNOS Ser608 Leu polymorphism and risk of these esophageal conditions. Our study suggests that the COX-2 8473 C allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(3):727–31)
Meta-analysis of Colorectal Cancer Gene Expression Profiling Studies Identifies Consistently Reported Candidate Biomarkers
Authors: Chan Simon K. , Griffith Obi L. , Tai Isabella T. , Jones Steven J.M. 
Published: March 2008

Abstract
Purpose: Elucidation of candidate colorectal cancer biomarkers often begins by comparing the expression profiles of cancerous and normal tissue by performing gene expression profiling. Although many such studies have been done, the resulting lists of differentially expressed genes tend to be inconsistent with each other, suggesting that there are some false positives and false negatives. One solution is to take the intersection of the lists from independent studies. However, often times, the statistical significance of the observed intersection are not assessed.
Methods: Recently, we developed a meta-analysis method that ranked differentially expressed genes in thyroid cancer based on the intersection among studies, total sample sizes, average fold change, and direction of differential expression. We applied an improved version of the method to 25 independent colorectal cancer profiling studies that compared cancer versus normal, adenoma versus normal, and cancer versus adenoma to highlight genes that were consistently reported as differentially expressed at a statistically significant frequency.
Results: We observed that some genes were consistently reported as differentially expressed with a statistically significant frequency (P &lt; 0.05) in cancer versus normal and adenoma versus normal comparisons but not in the cancer versus adenoma comparison.
Conclusion: Our meta-analysis method identified genes that were consistently reported as differentially expressed. A review of some of the candidates revealed genes described previously as having diagnostic and/or prognostic value as well as novel candidate biomarkers. The genes presented here will aid in the identification of highly sensitive and specific biomarkers in colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):543–52)
Cancer Risk in Children with Birth Defects and in Their Families: A Population Based Cohort Study of 5.2 Million Children from Norway and Sweden
Authors: Bjørge Tone , Cnattingius Sven , Lie Rolv Terje , Tretli Steinar , Engeland Anders 
Published: March 2008

Abstract
Background: Cancer and birth defects may share factors that influence risk. A malformation may involve physiologic changes or changes in lifestyle that might affect cancer risks.
Methods: In Norway and Sweden, the population-based medical birth and cancer registries were linked to identify subsequent cancer occurrence in children with birth defects and among their parents and siblings. Altogether, 5.2 million children and their families were included. The standardized incidence ratio (SIR) served as a measure of relative risk.
Results: There was an increased overall cancer risk in individuals with birth defects in the two countries [SIR, 1.7; 95% confidence interval (95% CI), 1.6-1.9], and the increased risk remained into early adulthood. Individuals with malformations in the nervous system were at increased risk of developing cancer in the brain/nervous system (Norway: SIR, 58; 95% CI, 41-80; Sweden: SIR, 8.3; 95% CI, 4.0-15), individuals with Down syndrome were at an increased risk of leukemia (Norway: SIR, 36; 95% CI, 26-48; Sweden: SIR, 36; 95% CI, 28-46), and there was an increased overall cancer risk for individuals with multiple birth defects (Norway: SIR, 5.5; 95% CI, 3.3-8.7; Sweden: SIR, 3.6; 95% CI, 2.2-5.4). There was no increased overall cancer risk among mothers (SIR, 1.0; 95% CI, 1.0-1.0), fathers (SIR, 1.0; 95% CI, 0.9-1.0), and siblings (SIR, 1.0; 95% CI, 0.9-1.1) of children with birth defects.
Conclusions: We observed an increased overall cancer risk in individuals with birth defects. The highest risks were seen for individuals with malformations in the nervous system, Down syndrome, and multiple defects. No increased overall cancer risk was seen among their parents or siblings. (Cancer Epidemiol Biomarkers Prev 2008;17(3):500–6)
NAT2*7 Allele Is a Potential Risk Factor for Adult Brain Tumors in Taiwanese Population
Authors: Liu H. Eugene , Hsiao Pei-Yu , Lee Ching-Chen , Lee Jen-Ai , Chen Hsiang-Yin 
Published: March 2008

Abstract
Arylamine N-acetyltransferase-2 (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and toxic compounds such as amine carcinogens. The association of NAT2 polymorphisms with adult brain tumors has been unclear. To investigate whether the NAT2 genotype is a risk factor of brain tumors, we determined the frequencies of three common polymorphisms in the NAT2 gene, NAT2*5 (T341C), NAT2*6 (G590A), and NAT2*7(G857A), in brain tumor patients and in age- and gender-matched control subjects (n = 27 in each group). Genotyping was carried out using PCR-RFLP and subjects were phenotyped as a fast or slow acetylator based on the genotypes. The odds ratio of NAT2*7 allele frequency was significantly higher in patients with brain tumor than in controls (odds ratio, 6.786; 95% confidence interval, 2.06-22.37; P = 0.003); in the mean time, NAT2*4/*7 genotype was significantly more common in the patient group than in controls (odds ratio, 6.19; 95% confidence interval, 1.68-22.79; P = 0.0039). The tumors in the patients with NAT2*7 allele tended to be high-grade astrocytoma or glioblastoma multiforme (P = 0.016). In conclusion, these data suggest that the presence of NAT2*7 allele might be a potential risk factor for the development of brain tumors in Taiwan. (Cancer Epidemiol Biomarkers Prev 2008;17(3):661–5)
Effect of Tissue Shipping on Plasma Cell Isolation, Viability, and RNA Integrity in the Context of a Centralized Good Laboratory Practice–Certified Tissue Banking Facility
Authors: Ahmann Gregory J. , Chng Wee Joo , Henderson Kimberly J. , Price-Troska Tammy L. , DeGoey Roberta W. , Timm Michael M. , Dispenzieri Angela , Greipp Philip R. , Sable-Hunt Alicia , Bergsagel Leif , Fonseca Rafael 
Published: March 2008

Abstract
The Multiple Myeloma Research Consortium has established a tissue bank for the deposition of bone marrow samples from patients with multiple myeloma to be mailed and processed under good laboratory practices. To date, over 1,000 samples have been collected. At this time, limited information is available on shipped bone marrow aspirates in regards to cell viability, yield, purity, and subsequent RNA yield and quality. To test these determinants, we did a pilot study on behalf of the Multiple Myeloma Research Consortium where samples were drawn at Mayo Clinic Rochester (MCR) pooled and split into two equal aliquots. One-half of each sample was processed following good laboratory practices compliant standard operating procedures, immediately after sample procurement, at MCR. The CD138+ cells were stored at -80°C as a Trizol lysate. The other half of the aspirate was sent overnight to Mayo Clinic Scottsdale where they were processed using identical standard operating procedures. The RNA was extracted and analyzed in a single batch at MCR. At both locations, samples were assayed for the following quality determinants: Viability was assessed using a three-color flow cytometric method (CD45, CD38, and 7-AAD). Cell counts were done to determine plasma cell recovery and post-sort purity determined by means of a slide-based immunofluorescent assay. RNA recovery and integrity was assessed using the Agilent Bioanalyzer. Lastly, gene expression profiles were compared to determine the signature emanating from the shipment of samples. Despite minor differences, our results suggest that shipment of samples did not significantly affect these quality determinants in aggregate. (Cancer Epidemiol Biomarkers Prev 2008;17(3):666–73)
International Correlation between Human Papillomavirus Prevalence and Cervical Cancer Incidence
Authors: Maucort-Boulch Delphine , Franceschi Silvia , Plummer Martyn ,   the IARC HPV Prevalence Surveys Study Group
Published: March 2008

AbstractData from population-based human papillomavirus (HPV) surveys in regions of low, intermediate, and high cervical cancer incidence were used to study the ecologic correlation between high-risk HPV prevalence and cervical cancer incidence. All the surveys were conducted by the IARC according to a standardized protocol for the collection of female population samples and detection of HPV DNA using PCR assay in a central laboratory. Cervical cancer incidence data were extracted, when available, from a cancer registry covering the surrounding or nearby area of the prevalence survey. Thirteen areas were included in this analysis. The relation between high-risk HPV prevalence and cervical cancer incidence was investigated within 10-year age groups from age 25 to 65 years. A Poisson regression model was used to predict cervical cancer incidence from HPV prevalence, and the strength of the correlation was assessed using Spearman’s rank correlation coefficient. The rank correlation was weakest in women ages 25 to 34 years and strongest in women ages 55 to 64 years. In addition, the prevalence of high-risk HPV was not able to predict cervical cancer incidence accurately in every country. Nevertheless, our data raise a concern about the cervical cancer burden in areas where reliable cervical cancer statistics do not exist but where the prevalence of high-risk HPV in women over age 45 is high. (Cancer Epidemiol Biomarkers Prev 2008;17(3):717–20)
Urinary 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine in Patients with Parasite Infection and Effect of Antiparasitic Drug in Relation to Cholangiocarcinogenesis
Authors: Thanan Raynoo , Murata Mariko , Pinlaor Somchai , Sithithaworn Paiboon , Khuntikeo Narong , Tangkanakul Walaluk , Hiraku Yusuke , Oikawa Shinji , Yongvanit Puangrat , Kawanishi Shosuke 
Published: March 2008

Abstract
Parasite infection of Opisthorchis viverrini is a major risk factor for cholangiocarcinoma. Our previous immunohistochemical studies showed that O. viverrini infection induced oxidative DNA lesions in the bile duct epithelium during cholangiocarcinoma development. The current study assessed the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), an oxidative DNA lesion, in the urine and leukocytes of O. viverrini–infected subjects and cholangiocarcinoma patients. Forty-nine O. viverrini–infected patients, 55 cholangiocarcinoma patients, and 17 healthy controls were enrolled in the study. We measured 8-oxodG levels in the urine and leukocytes of these subjects using an electrochemical detector coupled to high-performance liquid chromatography. O. viverrini–infected patients were assessed before treatment and 2 months and 1 year after praziquantel treatment. Urinary 8-oxodG levels were significantly higher in cholangiocarcinoma patients (6.83 ± 1.00 μg/g creatinine) than in O. viverrini–infected patients (4.45 ± 0.25 μg/g creatinine; P &lt; 0.05) and healthy subjects (3.03 ± 0.24 μg/g creatinine; P &lt; 0.01) and higher in O. viverrini–infected subjects than in healthy subjects (P &lt; 0.01). The urinary 8-oxodG levels in O. viverrini–infected patients significantly decreased 2 months after praziquantel treatment and were comparable with levels in healthy subjects 1 year after treatment. Urinary 8-oxodG levels were significantly correlated with leukocyte 8-oxodG levels, plasma nitrate/nitrite levels, and aspartate aminotransferase activity. In conclusion, this study, in addition to our previous studies, indicates that 8-oxodG formation by parasite infection may play an important role in cholangiocarcinoma development. Urinary 8-oxodG may be a useful biomarker to monitor not only infection but also carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(3):518–24)
Nonsteroidal Anti-inflammatory Drug Use and Serum Total Estradiol in Postmenopausal Women
Authors: Hudson Alana G. , Gierach Gretchen L. , Modugno Francesmary , Simpson Jennifer , Wilson John W. , Evans Rhobert W. , Vogel Victor G. , Weissfeld Joel L. 
Published: March 2008

AbstractLaboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index–adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(3):680–7)
Metabolism of the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone to Its Biomarker Total NNAL in Smokeless Tobacco Users
Authors: Hecht Stephen S. , Carmella Steven G. , Stepanov Irina , Jensen Joni , Anderson Amanda , Hatsukami Dorothy K. 
Published: March 2008

Abstract
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogens in smokeless tobacco products. NNK uptake by measurement of the urinary metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL) has been reported in many studies, but there are no data in the literature on the percentage of the NNK dose that is converted to NNAL in smokeless tobacco users. In this study, 15 male subjects abstained from tobacco use for 3 weeks before placing 2 g smokeless tobacco between their cheeks and gums for 30 min. They then continued abstinence and collected three consecutive 24-h urine samples. The amount of NNK in the tobacco before and after use was determined along with the amount in expectorated saliva. The NNK dose thus calculated was compared with the amount of total NNAL excreted in the next 72 h. These data, taken together with previous pharmacokinetic data, show that the percent conversion of NNK to total NNAL in smokeless tobacco users is ∼14% to 17%. This figure can be used to calculate daily exposure to NNK in smokeless tobacco users (∼6 μg). The results of this study also indicate that metabolic activation of NNK to intermediates that can react with DNA is its major pathway of metabolism in smokeless tobacco users. (Cancer Epidemiol Biomarkers Prev 2008;17(3):732–5)
Mutation of human plasminogen kringle 1–5 enhances antiangiogenic action via increased interaction with integrin αvβ3
Authors: Chang Po-Chiao , Chang Yu-Jia , Wu Hua-Lin , Chang Chin-Wei , Lin Chung-I. , Wang Wei-Chih , Shi Guey-Yueh 
Published: March 2008

SummaryAngiogenesis plays a primary role in tumor growth and metastasis. Angiostatin, a proteolytic fragment containing the first four kringle domains of human plasminogen, can inhibit angiogenesis. The anti-angiogenic activities of kringle 1–5 (K1–5) and kringle 5 fragments of plasminogen are greater than angiostatin in inhibiting angiogenesis and angiogenesis-dependent tumor growth. To further optimize kringle fragment anti-angiogenic activities, mutations were created at the potential glycosylation sites Asn-289 and Thr-346 and the Lys binding site, Leu-532, at kringle 5, including K1–5N289A (replacing Asn by Ala at residue 289), K1–5T346A, K1–5L532R, K1–5N289A/T346A, K1–5T346A/ L532R, K1–5N289A/L532R, and K1–5N289A/T346A/L532R. Wild-type and mutant K1–5 proteins were expressed successfully by the Pichia pastoris expression system. Native K1–5 from proteolytic cleavage and wild-type K1–5 have similar activity in inhibiting basic fibroblast growth factor-induced endothelial cell proliferation. Among these mutated proteins, K1–5N289A/ T346A/L532R exhibited the greatest effect in inhibiting endothelial cell proliferation and in inducing endothelial cell apoptosis. Integrin αvβ3-mediated adhesion of K1–5N289A/ T346A/L532R to endothelial cells was more greatly enhanced when compared to wild type K1–5. Furthermore, K1–5N289A/ T346A/L532R was most potent in inhibiting basic fibroblast growth factor-induced angiogenesis in Matrigel assay in vivo. Angiogenesis-dependent tumor growth was inhibited by systemically injected K1–5N289A/T346A/L532R into mice. These results demonstrate that alteration of glycosylation and Lys binding properties could increase the anti-angiogenic action of K1–5, possibly via enhanced interaction with integrin αvβ3 in endothelial cells.