bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive Metabolic Activation of the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Smokers
Authors: Stepanov Irina , Upadhyaya Pramod , Carmella Steven G. , Feuer Rachel , Jensen Joni , Hatsukami Dorothy K. , Hecht Stephen S. 
Published: July 2008

Abstract
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in both unburned tobacco and cigarette smoke. The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred to as total NNAL, is an established urinary biomarker of human NNK uptake. Metabolic activation of NNK to DNA adducts proceeds via α-hydroxylation pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid) are the principal end products of these pathways in rodents and primates. The purpose of this study was to determine NNK metabolic activation in smokers, as measured by the sum of keto acid and hydroxy acid, relative to total NNAL. To specifically identify NNK-derived keto acid and hydroxy acid, which are also formed from nicotine, we added [pyridine-D4]NNK to cigarettes that were originally low in NNK, and measured the deuterium-labeled metabolites in the urine of people who smoked these cigarettes. The total amount of [pyridine-D4]keto acid plus [pyridine-D4]hydroxy acid averaged 4.00 ± 2.49 nmol/24 h, whereas the average amount of total [pyridine-D4]NNAL was 0.511 ± 0.368 nmol/24 h. The results of this study show for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for ∼86% of total urinary excretion of NNK metabolites. The large interindividual variation in the excreted [pyridine-D4]keto acid and [pyridine-D4]hydroxy acid among 20 smokers strongly supports our hypothesis that some smokers activate NNK more extensively than others and that the ratio between biomarkers of metabolic activation and detoxification at a given dose of NNK could be a potential indicator of cancer risk.(Cancer Epidemiol Biomarkers Prev 2008;17(7):1764–73)
Performance of Amplified DNA in an Illumina GoldenGate BeadArray Assay
Authors: Cunningham Julie M. , Sellers Thomas A. , Schildkraut Joellen M. , Fredericksen Zachary S. , Vierkant Robert A. , Kelemen Linda E. , Gadre Madhura , Phelan Catherine M. , Huang Yifan , Meyer Jeffrey G. , Pankratz V. Shane , Goode Ellen L. 
Published: July 2008

Abstract
Whole genome amplification (WGA) offers a means to enrich DNA quantities for epidemiologic studies. We used an ovarian cancer study of 1,536 single nucleotide polymorphisms (SNPs) and 2,368 samples to assess performance of multiple displacement amplification (MDA) WGA using an Illumina GoldenGate BeadArray. Initial screening revealed successful genotyping for 93.4% of WGA samples and 99.3% of genomic samples, and 93.2% of SNPs for WGA samples and 96.3% of SNPs for genomic samples. SNP failure was predicted by Illumina-provided designability rank, %GC (P ≤ 0.002), and for WGA only, distance to telomere and Illumina-provided SNP score (P ≤ 0.002). Distance to telomere and %GC were highly correlated; adjustment for %GC removed the association between distance to telomere and SNP failure. Although universally high, per-SNP call rates were related to designability rank, SNP score, %GC, minor allele frequency, distance to telomere (P ≤ 0.01), and, for WGA only, Illumina-provided validation class (P &lt; 0.001). We found excellent concordance generally (&gt;99.0%) among 124 WGA:genomic replicates, 15 WGA replicates, 88 replicate aliquots of the same WGA preparation, and 25 genomic replicates. Where there was discordance, it was across WGA:genomic replicates but limited to only a few samples among other replicates suggesting the introduction of error. Designability rank and SNP score correlated with WGA:genomic concordance (P &lt; 0.001). In summary, use of MDA WGA DNA is feasible; however, caution is warranted regarding SNP selection and analysis. We recommend that biological SNP characteristics, notably distance to telomere and GC content (&lt;50% GC recommended), as well as Illumina-provided metrics be considered in the creation of GoldenGate assays using MDA WGA DNA. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1781–9)
A Prospective Study of Bowel Motility and Related Factors on Breast Cancer Risk
Authors: Maruti Sonia S. , Lampe Johanna W. , Potter John D. , Ready Ann , White Emily 
Published: July 2008

Abstract
Background: Estrogen is an established risk factor for breast cancer. Greater bowel motility has been associated with increased estrogen excretion and lower serum estrogen levels, suggesting that it may influence breast cancer risk. However, only one other epidemiologic study thus far, to our knowledge, has examined the relation between bowel motility and breast cancer risk.
Methods: We prospectively examined whether bowel motility, measured by self-reported frequency of bowel movements, and related factors (constipation, laxative use, water consumption, and dietary fiber intake) were associated with incidence of breast cancer among 28,586 postmenopausal women, ages 50 to 76 years, in the Vitamins and Lifestyle study. Cox proportional hazards models were used to estimate multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). From 2000 to 2005, 507 incident invasive breast cancers among the cohort were identified.
Results: Women with very frequent (≥3/d) bowel movements had a 46% decreased risk compared with 1/d women (RR, 0.54; 95% CI, 0.31-0.92), but the test for linear trend was not significant (Ptrend = 0.41). Constipation was nonsignificantly associated with increased risk (RR, 1.30 for ≥1/wk versus &lt;1/y; 95% CI, 0.87-1.95). No statistically significant associations were observed for the other study exposures: 10-year chemical laxative use, 10-year use of fiber laxatives, water consumption, and dietary fiber intake.
Conclusion: This study adds limited support to the hypothesis that increased bowel motility lowers breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1746–50)
Successful Coordination and Execution of Nontherapeutic Studies in a Cooperative Group Setting: Lessons Learned from Children's Oncology Group Studies
Authors: Carter Andrea , Landier Wendy , Schad Amy , Moser Allison , Schaible Alexandra , Hanby Cara , Kurian Seira , Wong F. Lennie , Villaluna Doojduen , Bhatia Smita 
Published: July 2008

Abstract
The immense progress made in childhood cancer survival has been due to the systematic and efficient conduct of large multicenter therapeutic trials, using the infrastructure developed by national cooperative groups. These therapeutic trials have been successful, in part due to the high participation rates by the participating member institutions. However, participation in nontherapeutic trials in the cooperative group setting has lagged behind that of therapeutic trials for a variety of reasons, such as lack of institutional resources, leading to low priority given to such activities. The purpose of this report is to share some of the methods developed and successfully implemented by a coordinating center (City of Hope National Medical Center) to maximize institutional participation and patient enrollment and to standardize data collection and quality control, in order to ensure the successful execution of two large, extramurally funded, cooperative group nontherapeutic studies. To date, over 175 institutions have obtained regulatory approval for the protocols showcased here, accrual has been on target, and completeness and quality of the collected data have been excellent. The successful execution of these nontherapeutic studies shows the advantages of diverse study publicity techniques, detailed standardized operating procedures, and effective utilization of technological resources. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1665–73)
Diet, Autophagy, and Cancer: A Review
Authors: Singletary Keith , Milner John 
Published: July 2008

Abstract
A host of dietary factors can influence various cellular processes and thereby potentially influence overall cancer risk and tumor behavior. In many cases, these factors suppress cancer by stimulating programmed cell death. However, death not only can follow the well-characterized type I apoptotic pathway but also can proceed by nonapoptotic modes such as type II (macroautophagy-related) and type III (necrosis) or combinations thereof. In contrast to apoptosis, the induction of macroautophagy may contribute to either the survival or death of cells in response to a stressor. This review highlights current knowledge and gaps in our understanding of the interactions among bioactive food constituents, autophagy, and cancer. Whereas a variety of food components including vitamin D, selenium, curcumin, resveratrol, and genistein have been shown to stimulate autophagy vacuolization, it is often difficult to determine if this is a protumorigenic or antitumorigenic response. Additional studies are needed to examine dose and duration of exposures and tissue specificity in response to bioactive food components in transgenic and knockout models to resolve the physiologic implications of early changes in the autophagy process. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1596–610)
Testing a Multigene Signature of Prostate Cancer Death in the Swedish Watchful Waiting Cohort
Authors: Mucci Lorelei A. , Pawitan Yudi , Demichelis Francesca , Fall Katja , Stark Jennifer R. , Adami Hans-Olov , Andersson Swen-Olof , Andrén Ove , Eisenstein Anna , Holmberg Lars , Huang Wei , Kantoff Philip W. , Kim Robert , Perner Sven , Stampfer Meir J. , Johansson Jan-Erik , Rubin Mark A. 
Published: July 2008

Abstract
Although prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Örebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the markers in tumor tissue by immunohistochemistry and stratified the cohort by quintiles according to risk classification. We accounted for clinical variables (age, Gleason, nuclear grade, and tumor volume) using Cox regression and calculated receiver operator curves to compare discriminatory ability. The hazard ratio of prostate cancer death increased with increasing risk classification by the multigene model, with a 16-fold greater risk comparing highest-risk versus lowest-risk strata, and predicted outcome independent of clinical factors (P = 0.002). The best discrimination came from combining information from the multigene markers and clinical data, which perfectly classified the lowest-risk stratum where no one developed lethal disease; using the two lowest-risk groups as reference, the hazard ratio (95% confidence interval) was 11.3 (4.0-32.8) for the highest-risk group and difference in mortality at 15 years was 60% (50-70%). The combined model provided greater discriminatory ability (area under the curve = 0.78) than the clinical model alone (area under the curve = 0.71; P = 0.04). Molecular tumor markers can add to clinical variables to help distinguish lethal and indolent prostate cancer and hold promise to guide treatment decisions. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1682–8)
No Reduction in C-Reactive Protein following a 12-Month Randomized Controlled Trial of Exercise in Men and Women
Authors: Campbell Kristin L. , Campbell Peter T. , Ulrich Cornelia M. , Wener Mark , Alfano Catherine M. , Foster-Schubert Karen , Rudolph Rebecca E. , Potter John D. , McTiernan Anne 
Published: July 2008

Abstract
Low-grade systemic inflammation is suggested to play a role in the development of several chronic diseases including cancer. Higher levels of physical activity and lower adiposity have been associated with reduced levels of markers of systemic inflammation, such as C-reactive protein (CRP); however, reductions in CRP have not been consistently observed in randomized controlled trials of exercise.
Purpose: To examine the effect of a 12-month aerobic exercise intervention on CRP levels in men and women.
Methods: One hundred two men and 100 women, sedentary and of ages 40 to 75 years, with mean body mass index (BMI) of 29.9 and 28.7 kg/m2, respectively, were randomly assigned to a 12-month moderate-to-vigorous aerobic exercise intervention (6 d/wk, 60 min/d, 60-85% maximum heart rate) or control group. Fasting blood samples were collected at baseline and at 12 months. CRP levels were measured by high-sensitivity latex-enhanced nephelometry.
Results: At baseline, CRP was 1.16 and 2.11 mg/L for men and women, respectively, and CRP was correlated with percent body fat (r = 0.48, P ≤0.001), BMI (r = 0.37, P ≤ 0.001), and aerobic fitness (r = −0.49, P ≤ 0.001). No intervention effects were observed for CRP in men or women, or when stratified by baseline BMI (&lt;30 versus ≥30 kg/m2), baseline CRP (&lt;3 versus ≥3 mg/L), or change in body weight, body composition, or aerobic fitness.
Conclusion: A 12-month moderate-to-vigorous aerobic exercise intervention did not affect CRP levels in previously sedentary men or women with average-risk CRP values at baseline. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1714–8)
Ethnicity and Risk for Colorectal Cancers Showing Somatic BRAF V600E Mutation or CpG Island Methylator Phenotype
Authors: English Dallas R. , Young Joanne P. , Simpson Julie A. , Jenkins Mark A. , Southey Melissa C. , Walsh Michael D. , Buchanan Daniel D. , Barker Melissa A. , Haydon Andrew M. , Royce Simon G. , Roberts Aedan , Parry Susan , Hopper John L. , Jass Jeremy J. , Giles Graham G. 
Published: July 2008

Abstract
Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. Few epidemiologic studies have investigated risk factors for these tumors. We conducted a cohort study of 41,328 residents of Melbourne, Australia that included 9,939 participants of southern European origin and 31,389 of Anglo-Celtic origin. Colorectal adenocarcinomas were identified from population-based cancer registries. BRAF V600E mutation in tumors was determined using a PCR-based allelic discrimination method. Tumors were classified as CIMP positive when at least three of five markers (RUNX3, CACNA1G, SOCS1, NEUROG1, and IGF2) were methylated according to MethyLight analysis. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression with adjustment for risk factors for colorectal cancer. During follow-up, 718 participants were diagnosed with colorectal cancer. CIMP assays were done for 579 and BRAF V600E mutation testing for 582. After adjustment for other risk factors, when compared with people of Anglo-Celtic origin, those of southern European origin had lower incidence of colorectal cancer that had CIMP (HR, 0.32; 95% CI, 0.16-0.67) or BRAF mutations (HR, 0.30; 95% CI, 0.16-0.58) but similar incidence of colorectal cancer without CIMP (HR, 0.86; 95% CI, 0.70-1.05) or BRAF (HR, 0.90; 95% CI, 0.74-1.11). People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1774–80)
GSTM1 and GSTT1 Gene Deletions and the Risk for Nasopharyngeal Carcinoma in Han Chinese
Authors: Guo Xiuchan , O'Brien Stephen J. , Zeng Yi , Nelson George W. , Winkler Cheryl A. 
Published: July 2008

Abstract
Southern China is a major nasopharyngeal carcinoma–endemic region. Environmental factors and genetic susceptibility contribute to nasopharyngeal carcinoma development in this area. Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be a risk factor for nasopharyngeal carcinoma. To investigate the roles of genetic variations of GSTM1 and GSTT1 in nasopharyngeal carcinoma susceptibility in the Chinese population, we conducted a case-control study of 350 nasopharyngeal carcinoma cases and 622 controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assays. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% CI). No significant association was observed for either GSTM1- or GSTT1-null genotype independently in the contribution to nasopharyngeal carcinoma risk. To explore possible joint effects of the GSTM1- and GSTT1-null polymorphisms with each other and with other risk factors for nasopharyngeal carcinoma, we examined the association between each combined genotype and the risk for nasopharyngeal carcinoma stratified by gender and EBV replication status. We found that individuals who carried GSTM1/GSTT1–double null genotype had a higher risk for nasopharyngeal carcinoma in the male population (odds ratio, 1.76; 95% confidence interval, 1.04-2.97; P = 0.03); however, this was not significant after correction for multiple comparisons. No statistical difference was found between cases and controls in females and the subpopulation positive for immunoglobulin A antibodies to EBV capsid antigen for combined genotypes. Our results suggest that the GSTM1/GSTT1–double null genotype may be a risk factor for nasopharyngeal carcinoma among males in southern China, but this result warrants confirmation in other studies. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1760–3)
Polymorphisms in Genes Involved in Sex Hormone Metabolism, Estrogen Plus Progestin Hormone Therapy Use, and Risk of Postmenopausal Breast Cancer
Authors: Diergaarde Brenda , Potter John D. , Jupe Eldon R. , Manjeshwar Sharmila , Shimasaki Craig D. , Pugh Thomas W. , DeFreese Daniele C. , Gramling Bobby A. , Evans Ilonka , White Emily 
Published: July 2008

AbstractHormone therapy, estrogen plus progestin (E+P) particularly, is associated with increased risk of breast cancer. Functionally relevant polymorphisms in genes involved in sex hormone metabolism may alter exposure to exogenous sex hormones and affect risk of postmenopausal breast cancer. We evaluated associations of common polymorphisms in genes involved in estrogen and/or progesterone metabolism, E+P use, and their interactions with breast cancer risk in a case-control study of postmenopausal women (324 cases; 651 controls) nested within the VITAL cohort. None of the polymorphisms studied was, by itself, statistically significantly associated with breast cancer risk. E+P use was significantly associated with increased breast cancer risk (≥10 years versus never; odds ratio, 1.9; 95% confidence interval, 1.3-2.8; Ptrend = 0.0002). Statistically significant interactions between CYP1A1 Ile462Val (Pinteraction = 0.04), CYP1A1 MspI (Pinteraction = 0.003), CYP1B1 Val432Leu (Pinteraction = 0.007), CYP1B1 Asn453Ser (Pinteraction = 0.04) and PGR Val660Leu (Pinteraction = 0.01), and E+P use were observed. The increased risk of breast cancer associated with E+P use was greater among women with at least one rare allele of the CYP1A1 Ile462Val, CYP1A1 MspI, CYP1B1 Asn453Ser, and PGR Val660Leu polymorphisms than among women homozygous for the common allele of these polymorphisms. Risk of breast cancer increased little with increasing years of E+P use among women with at least one CYP1B1 Val432 allele; a large increase in risk was seen among women homozygous for CYP1B1 Leu432. Our results support the hypothesis that specific polymorphisms in genes involved in sex hormone metabolism may modify the effect of E+P use on breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1751–9)
Limits of Detection of Chemopreventive Efficacy: Karyometry of Skin Biopsies
Authors: Bartels Peter H. , Yozwiak Michael L. , Bartels Hubert G. , Liu Yun , Hess Lisa M. , Alberts David S. 
Published: July 2008

Abstract
Objective: This study was designed to establish estimates of the smallest effects due to chemopreventive intervention detectable by karyometry in skin biopsies.
Methods: Estimates of the smallest change of statistical significance and estimates of the power of the test were derived for several key features descriptive of the distribution of nuclear chromatin. Results from triplicate biopsies from the same case were used to provide estimates of the within-case, biopsy-to-biopsy variance.
Results: Generally, a change in feature value due to chemopreventive intervention can be statistically secured when it amounts to 5% to 10%. In clinical trials where matched baseline and end of study biopsies from the same cases are available, paired comparison ANOVA can detect a 2% change on samples of 25 cases. Establishing efficacy in individual cases requires a change in feature values on the order of 10% to 15%.
Conclusions: Karyometry provides a sensitive, quantitative method for the assessment of efficacy of chemoprevention. The effects of within-case, biopsy-to-biopsy variance need to be considered only in the evaluation of individual cases and are on the order of 5% in skin biopsies. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1689–95)
Genetic Polymorphisms of CYP2E1 and Risk of Colorectal Adenomas in the Self Defense Forces Health Study
Authors: Morita Makiko , Tabata Shinji , Tajima Osamu , Yin Guang , Abe Hiroshi , Kono Suminori 
Published: July 2008

Abstract
CYP2E1 is an enzyme involved in the metabolism of N-nitrosamines and other carcinogenic substances. Functional RsaI and 96-bp insertion polymorphisms in 5′-flanking region have drawn interest in relation to the risk of colorectal cancer. We investigated the relation of these genetic polymorphisms and colorectal adenoma, a well-established precursor lesion of colorectal cancer. Subjects were 455 cases of colorectal adenomas and 1,052 controls of normal colonoscopy among men receiving a preretirement health examination in the Self Defense Forces. Genotypes were determined by either PCR-RFLP or PCR method. Statistical adjustment was made for smoking, alcohol use, body mass index, physical activity, and others. Individuals with RsaI c2 allele showed a decreased risk of proximal colon adenomas; adjusted odds ratios (95% confidence interval) of proximal and distal adenomas for the c1/c2 or c2/c2 genotype versus c1/c1 was 0.61 (0.41-0.88) and 0.95 (0.71-1.27), respectively. CYP2E1 96-bp insertion allele was associated with an increased risk of large (≥ 5 mm) adenomas; adjusted odds ratios (95% confidence interval) of large and small adenomas for having at least one insertion allele were 1.41 (1.03-1.94) and 0.94 (0.71-1.25), respectively. A suggestive effect modification was noted for alcohol consumption on the association between RsaI polymorphism and proximal adenomas (Pinteraction = 0.09) as well as on the association between 96-bp insertion and large adenomas (Pinteraction = 0.05). These findings indicate that variation in activity and inducibility of CYP2E1 contribute to the development of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1800–7)