bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Genome Amplification Enables Accurate Genotyping for Microarray-Based High-Density Single Nucleotide Polymorphism Array
Authors: Jasmine Farzana , Ahsan Habibul , Andrulis Irene L. , John Esther M. , Chang-Claude Jenny , Kibriya Muhammad G. 
Published: December 2008

Abstract
In large-scale genome-wide association studies based on high-density single nucleotide polymorphism (SNP) genotyping array, the quantity and quality of available genomic DNA (gDNA) is a practical problem. We examined the feasibility of using the Multiple Displacement Amplification (MDA) method of whole-genome amplification (WGA) for such a platform. The Affymetrix Early Access Mendel Nsp 250K GeneChip was used for genotyping 224,940 SNPs per sample for 28 DNA samples. We compared the call concordance using 14 gDNA samples and their corresponding 14 WGA samples. The overall mean genotype call rates in gDNA and the corresponding WGA samples were comparable at 97.07% [95% confidence interval (CI), 96.17-97.97] versus 97.77% (95% CI, 97.26-98.28; P = 0.154), respectively. Reproducibility of the platform, calculated as concordance in duplicate samples, was 99.45%. Overall genotypes for 97.74% (95% CI, 97.03-98.44) of SNPs were concordant between gDNA and WGA samples. When the analysis was restricted to well-performing SNPs (successful genotyping in gDNA and WGA in &gt;90% of samples), 99.11% (95% CI, 98.80-99.42) of the SNPs, on average, were concordant, and overall a SNP showed a discordant call in 0.92% (95% CI, 0.90-0.94) of paired samples. In a pair of gDNA and WGA DNA, similar concordance was reproducible on Illumina's Infinium 610 Quad platform as well. Although copy number analysis revealed a total of seven small telomeric regions in six chromosomes with loss of copy number, the estimated genome representation was 99.29%. In conclusion, our study confirms that high-density oligonucleotide array-based genotyping can yield reproducible data and MDA-WGA DNA products can be effectively used for genome-wide SNP genotyping analysis. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3499–508)
Effect of Physical Activity on Breast Cancer Risk: Findings of the Japan Collaborative Cohort Study
Authors: Suzuki Sadao , Kojima Masayo , Tokudome Shinkan , Mori Mitsuru , Sakauchi Fumio , Fujino Yoshihisa , Wakai Kenji , Lin Yingsong , Kikuchi Shogo , Tamakoshi Koji , Yatsuya Hiroshi , Tamakoshi Akiko ,   for the Japan Collaborative Cohort Study Group
Published: December 2008

AbstractPurpose: This study aimed to examine prospectively the association between physical activity and breast cancer risk in a non-Western population.Methods: We analyzed data from the Japan Collaborative Cohort Study, which included 30,157 women, ages 40 to 69 years at baseline (1988-1990), who reported no previous history of breast cancer, and provided information on their walking and exercise habits. The subjects were followed prospectively from enrollment until 2001 (median follow-up period, 12.4 years). Breast cancer incidence during this period was confirmed using records held at population-based cancer registries. The Cox proportional hazards model was used to estimate the hazard ratio (HR) for the association of breast cancer incidence with physical activity.Results: During the 340,055 person-years of follow-up, we identified 207 incident cases of breast cancer. The most physically active group (who walked for ≥1 hour per day and exercised for ≥1 hour per week) had a lower risk of breast cancer (HR, 0.45; 95% confidence interval, 0.25-0.78) compared with the least active group after adjusting for potential confounding factors. The inverse association of exercise on breast cancer was stronger among those who walked for ≥1 hour per day than those who walked for &lt;1 hour per day (P = 0.042). These results were not significantly modified by menopausal status or body mass index (BMI).Conclusions: Our analysis provided evidence that physical activity decreased the risk of breast cancer. Walking for 1 hour per day and undertaking additional weekly exercise both seemed to be protective against breast cancer, regardless of menopausal status or BMI. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3396–401)
Polymorphism in theIL18Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women
Authors: Palmieri Rachel T. , Wilson Melanie A. , Iversen Edwin S. , Clyde Merlise A. , Calingaert Brian , Moorman Patricia G. , Poole Charles , Anderson A. Rebecca , Anderson Stephanie , Anton-Culver Hoda , Beesley Jonathan , Hogdall Estrid , Brewster Wendy , Carney Michael E. , Chen Xiaoqing , Chenevix-Trench Georgia , Chang-Claude Jenny , Cunningham Julie M. , DiCioccio Richard A. , Doherty Jennifer A. , Easton Douglas F. , Edlund Christopher K. , Gayther Simon A. , Gentry-Maharaj Aleksandra , Goode Ellen L. , Goodman Marc T. , Kjaer Susanne Kruger , Hogdall Claus K. , Hopkins Michael P. , Jenison Eric L. , Blaakaer Jan , Lurie Galina , McGuire Valerie , Menon Usha , Moysich Kirsten B. , Ness Roberta B. , Pearce Celeste Leigh , Pharoah Paul D.P. , Pike Malcolm C. , Ramus Susan J. , Rossing Mary Anne , Song Honglin , Terada Keith Y. , VanDenBerg David , Vierkant Robert A. , Wang-Gohrke Shan , Webb Penelope M. , Whittemore Alice S. , Wu Anna H. , Ziogas Argyrios , Berchuck Andrew , Schildkraut Joellen M. ,   On behalf of the Ovarian Cancer Association Consortium; Australian Cancer Study (Ovarian Cancer Group); Australian Ovarian Cancer Study Group
Published: December 2008

AbstractOver 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a &lt;25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567–72)
Common Single-Nucleotide Polymorphisms in DNA Double-Strand Break Repair Genes and Breast Cancer Risk
Authors: Pooley Karen A. , Baynes Caroline , Driver Kristy E. , Tyrer Jonathan , Azzato Elizabeth M. , Pharoah Paul D.P. , Easton Douglas F. , Ponder Bruce A.J. , Dunning Alison M. 
Published: December 2008

AbstractThe proteins involved in homologous recombination are instrumental in the error-free repair of dsDNA breakages, and common germ-line variations in these genes are, therefore, potential candidates for involvement in breast cancer development and progression. We carried out a search for common, low-penetrance susceptibility alleles by tagging the common variation in 13 genes in this pathway in a two-stage case-control study. We genotyped 100 single-nucleotide polymorphisms (SNP), tagging the 655 common SNPs in these genes, in up to 4,470 cases and 4,560 controls from the SEARCH study. None of these tagging SNPs was associated with breast cancer risk, with the exception of XRCC2 rs3218536, R188H, which showed some evidence of a protective association for the rare allele [per allele odds ratio, 0.89; 95% confidence intervals (95% CI), 0.80-0.99; P trend = 0.03]. Further analyses showed that this effect was confined to a risk of progesterone receptor positive tumors (per rare allele odds ratio, 0.78; 95% CI, 0.66-0.91; P trend = 0.002). Several other SNPs also showed receptor status-specific susceptibility and evidence of roles in long-term survival, with the rare allele of BRIP1 rs2191249 showing evidence of association with a poorer prognosis (hazard ratio per minor allele, 1.20; 95% CI, 1.07-1.36; P trend = 0.002). In summary, there was little evidence of breast cancer susceptibility with any of the SNPs studied, but larger studies would be needed to confirm subgroup effects. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3482–9)
Melatonin as a Biomarker of Circadian Dysregulation
Authors: Mirick Dana K. , Davis Scott 
Published: December 2008

AbstractIt would be most useful to identify a biomarker of circadian dysregulation that could be used in epidemiologic studies of the effects of circadian disruption in humans. An indicator of circulating melatonin level has been shown to be a good biomarker of circadian dysregulation and has been associated with nightshift work and exposure to light-at-night in both laboratory-based and field studies. Among other circadian markers (such as core body temperature), it remains comparatively robust in the presence of various external influences. It can be reliably measured directly and indirectly through its metabolites in urine, blood, and saliva. Urinary melatonin has been shown to be stable over time, making it useful in epidemiologic studies in which laboratory processing is not immediately available, as well as studies of cancer with long latency periods. Several studies have shown melatonin to be useful in measuring diurnal type, which is of increasing interest as it becomes more apparent that successful adaptation to shift work may be dependent on diurnal preference. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3306–13)
Influence of Evolution in Tumor Biobanking on the Interpretation of Translational Research
Authors: Barnes Rebecca O. , Parisien Michelle , Murphy Leigh C. , Watson Peter H. 
Published: December 2008

AbstractPurpose: Translational cancer research increasingly relies on human tissue biospecimens and this has coincided with a shift in tissue biobanking approach. Newer biobanks (post year 2000) deploy standard operating procedures to reduce variability around biospecimen collection. Because current translational research is based on pre-2000 and post-2000 era biospecimens, we consider whether the collection era may influence gene expression data.Design: We compared the range of breast tumor collection times from pre-2000 and post-2000 era biobanks and compared estrogen receptor (ER) protein expression with collection time. We then collected 10 breast tumor biospecimens under a standardized protocol and examined whether the expression of c-myc and ER was influenced by storage on ice ≤24 hours.Results: The range of collection times achieved at a pre-2000 versus post-2000 era biobank differed. Thirty-two percent of biospecimens were cryopreserved within 30 minutes at the pre-2000 era biobank versus 76% at the post-2000 era biobank. Collection time and ER protein level was inversely correlated (r = −0.19, P = 0.025; n = 137). We observed a wide range in initial c-myc and ER mRNA levels (50- versus 130-fold). Although mRNA levels of both genes declined with increasing collection time, the rate of change differed because c-myc was significantly reduced after 24 hours (mean reduction to 79% of initial) versus ER (94% of initial).Conclusion: The overall shift in biobanking around the year 2000 is reflected in the ranges of collection times associated with pre-2000 and post-2000 era biobanks. Because collection time can differentially alter gene expression, the biospecimen collection era should be considered in gene expression studies. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3344–50)
Risk Factors for Classical Kaposi Sarcoma in a Population-based Case-control Study in Sicily
Authors: Anderson Lesley A. , Lauria Carmela , Romano Nino , Brown Elizabeth E. , Whitby Denise , Graubard Barry I. , Li Yan , Messina Angelo , Gafà Lorenzo , Vitale Francesco , Goedert James J. 
Published: December 2008

Abstract
Background: Classical Kaposi sarcoma is a rare complication of Kaposi sarcoma-associated herpes virus (KSHV) infection. We conducted a population-based, frequency-matched case-control study in Sicily to further investigate the reported inverse relationship between smoking and classical Kaposi sarcoma and to identify other factors associated with altered risk.
Methods: All incident, histologically confirmed classical Kaposi sarcoma cases in Sicily were eligible. A two-stage cluster sample design was applied to select population controls. KSHV seropositivity was determined using four antibody assays (K8.1 and orf73 enzyme immunoassays and two immunofluorenscence assays). Using SAS-callable SUDAAN, we compared the characteristics of classical Kaposi sarcoma cases and KSHV-seropositive controls. Odds ratios (OR) and 95% confidence intervals (CI) are presented.
Results: In total, 142 classical Kaposi sarcoma cases and 123 KSHV-seropositive controls were recruited. Current cigarette smoking was associated with reduced risk of classical Kaposi sarcoma amongst males (OR, 0.20; 95% CI, 0.06-0.67). Edema was associated with classical Kaposi sarcoma, but only when it presented on the lower extremities (OR, 3.65; 95% CI, 1.62-8.23). Irrespective of presentation site, diabetes and oral corticosteroid medications were associated with increased risk (OR, 4.73; 95% CI, 2.02-11.1 and OR, 2.34; 95% CI, 1.23-4.45, respectively). Never smoking, diabetes, and oral corticosteroid medication use were all independently associated with classical Kaposi sarcoma risk.
Discussion: We confirmed previous reports that cigarette smoking was associated with a reduced risk of classical Kaposi sarcoma, and we found that risk was lowest among current smokers. We also found that classical Kaposi sarcoma risk was strongly and independently associated with oral corticosteroid use and diabetes. Corroboration of these observations and investigation of possible underlying mechanisms are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3435–43)
Folate Intake and Risk of Breast Cancer by Estrogen and Progesterone Receptor Status in a Swedish Cohort
Authors: Larsson Susanna C. , Bergkvist Leif , Wolk Alicja 
Published: December 2008

AbstractBackground: Folate is a B vitamin involved in one-carbon metabolism and has been postulated to influence the risk of breast cancer. However, epidemiologic studies of folate intake in relation to breast cancer risk are inconclusive. We examined the association between dietary folate intake and the risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumor in the Swedish Mammography Cohort.Methods: Our study population consisted of 61,433 women who completed a food frequency questionnaire at baseline (1987-1990) and again in 1997. Cox proportional hazards models were used to estimate rate ratios (RR) with 95% confidence intervals (95% CI).Results: During an average of 17.4 years of follow-up, 2,952 incident cases of invasive breast cancer were ascertained. We observed no association between dietary folate intake and risk of total breast cancer or ER+/PR+ or ER-/PR- tumors. The multivariate RR of total breast cancer comparing extreme quintiles of folate intake was 1.01 (95% CI, 0.90-1.13; Ptrend = 0.84). However, folate intake was inversely associated with risk of ER+/PR- breast cancer (n = 417 cases; RR for highest versus lowest quintile, 0.79; 95% CI, 0.59-1.07; Ptrend = 0.01). Results did not vary by alcohol intake or menopausal status.Conclusions: These findings do not support an overall association between folate intake and risk of breast cancer but suggest that folate intake may be inversely associated with ER+/PR− tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3444–9)
Perils in the Use of Linkage Disequilibrium for Fine Gene Mapping: Simple Insights from Population Genetics
Authors: Gorroochurn Prakash 
Published: December 2008

Abstract
It is generally believed that genome-wide association (GWA) studies stand a good chance for finding susceptibility genes for common complex diseases. Although the results thus far have been somewhat promising, there are still many inherent difficulties and many initial associations do not get replicated. The common strategy in GWA studies has been that of selecting the most statistically significant single nucleotide polymorphisms with the hope that these will be very physically close to causal variants because of strong linkage disequilibrium (LD). Using simple ideas from population genetics, this commentary explains why this strategy can be misleading. It argues that there is an intrinsic problem in the way LD is currently used for fine-mapping. This is because most of the metrics that are currently used to measure LD are inadequate, as they do not take into account evolutionary variables that shape the LD structure of the human genome. Recent research on another metric, based on Malécot's model for isolation by distance, holds considerable promise for GWA studies and merits more serious consideration by geneticists. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3292–7)
Correlation between the Urine Profile of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone Metabolites and N7-Methylguanine in Urothelial Carcinoma Patients
Authors: Lee Hui-Ling , Hsueh Yu-Mei , Chung Chi-Jung , Pu Yeong-Shiau , Chang Louis W. , Hsieh Dennis Paul Hsientang , Liou Saou-Hsing , Lin Pinpin 
Published: December 2008

Abstract
A major carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is present in cigarette smoke and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), is used as an exposure biomarker for environmental tobacco smoke (ETS). This metabolite (NNAL) can be either detoxified into glucuronidated NNAL (NNAL-Gluc) or activated into an unstable reactive metabolite that methylates DNA along with formation of 4-hydroxy-4-(3-pyridyl)-butyric acid [hydroxy acid (HA)]. Therefore, the carcinogenic risk associated with ETS exposure is greatly modulated by individual variations in metabolic activation and detoxification capabilities. In this study, we defined the urinary HA/total NNAL [HA/total NNAL] ratio as the activation index and NNAL-Gluc/free NNAL [(total NNAL-free NNAL)/free NNAL] ratio as the detoxification index of NNK. The major methylated DNA adduct N7-methylguanine (N7-MeG), considered as the carcinogenic biomarker for cigarette smoking, was excreted in urine. The objective of this study was to investigate the effects of these metabolic indexes of NNK on N7-MeG urinary excretion in a population of urothelial carcinoma patients. Urinary levels of total NNAL (free NNAL plus NNAL-Gluc), free NNAL, HA, and N7-MeG were positively correlated with smoking. Furthermore, activation index and detoxification index correlated positively and negatively with N7-MeG levels, respectively. Our results suggest that these metabolic indices may represent the phenotype of individual metabolism capability and modulate the carcinogenic risk of ETS exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3390–5)
No Association of Single Nucleotide Polymorphisms in One-Carbon Metabolism Genes with Prostate Cancer Risk
Authors: Stevens Victoria L. , Rodriguez Carmen , Sun Juzhong , Talbot Jeffrey T. , Thun Michael J. , Calle Eugenia E. 
Published: December 2008

AbstractOne-carbon metabolism mediates the interconversion of folates for the synthesis of precursors used in DNA synthesis, repair, and methylation. Inadequate folate nutrition or compromised metabolism can disrupt these processes and facilitate carcinogenesis. In this study, we investigated associations of 39 candidate single nucleotide polymorphisms (SNP) in 9 one-carbon metabolism genes with risk of prostate cancer using 1,144 cases and 1,144 controls from the Cancer Prevention Study-II Nutrition Cohort. None of these SNPs were significantly associated with prostate cancer risk, either overall or in cases with advanced prostate cancer. Thus, our findings do not support the hypothesis that common genetic variation in one-carbon metabolism genes influences prostate cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3612–4)
Gene Signaling Pathways Mediating the Opposite Effects of Prepubertal Low-Fat and High-Fat n-3 Polyunsaturated Fatty Acid Diets on Mammary Cancer Risk
Authors: Olivo-Marston Susan E. , Zhu Yuelin , Lee Richard Y. , Cabanes Anna , Khan Galam , Zwart Alan , Wang Yue , Clarke Robert , Hilakivi-Clarke Leena 
Published: December 2008

AbstractIn rats, prepubertal exposure to low-fat diet containing n-3 polyunsaturated fatty acids (PUFA) reduces mammary cell proliferation, increases apoptosis, and lowers risk of mammary tumors in adulthood, whereas prepubertal high-fat n-3 PUFA exposure has opposite effects. To identify signaling pathways mediating these effects, we performed gene microarray analyses and determined protein levels of genes related to mammary epithelial cell proliferation. Nursing female rats and rat pups were fed low-fat (16% energy from fat) or high-fat (39% energy from fat) n-3 or n-6 PUFA diets between postnatal days 5 and 24. cDNA gene expression microarrays were used to identify global changes in the mammary glands of 50-day-old rats. Differences in gene expression were confirmed by real-time quantitative PCR, and immunohistochemistry was used to assess changes in the peroxisome proliferator–activated receptor γ and cyclin D1 levels. DNA damage was determined by 8-hydroxy-2′-deoxyguanosine assay. Expressions of the antioxidant genes thioredoxin, heme oxygenase, NADP-dependent isocitrate dehydrogenase, and metallothionein III, as well as peroxisome proliferator–activated receptor γ protein, were increased in the mammary glands of 50-day-old rats prepubertally fed the low-fat n-3 PUFA diet. Prepubertal exposure to the high-fat n-3 PUFA diet increased DNA damage and cyclin D1 protein and reduced expression of BRCA1 and cardiotrophin-1. Reduction in mammary tumorigenesis among rats prepubertally fed a low-fat n-3 PUFA diet was associated with an up-regulation of antioxidant genes, whereas the increase in mammary tumorigenesis in the high-fat n-3 PUFA fed rats was linked to up-regulation of genes that induce cell proliferation and down-regulation of genes that repair DNA damage and induce apoptosis.