bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity, Recreational Physical Activity, and Risk of Pancreatic Cancer In a Large U.S. Cohort
Authors: Patel Alpa V. , Rodriguez Carmen , Bernstein Leslie , Chao Ann , Thun Michael J. , Calle Eugenia E. 
Published: September 2005

Abstract
Background: Obesity and physical activity, in part through their effects on insulin sensitivity, may be modifiable risk factors for pancreatic cancer.
Methods: The authors analyzed data from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to examine the association between measures of adiposity, recreational physical activity, and pancreatic cancer risk. Information on current weight and weight at age 18, location of weight gain, and recreational physical activity were obtained at baseline in 1992 via a self-administered questionnaire for 145,627 men and women who were cancer-free at enrollment. During the 7 years of follow-up, 242 incident pancreatic cancer cases were identified among these participants. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including personal history of diabetes and smoking.
Results: We observed an increased risk of pancreatic cancer among obese [body mass index (BMI) ≥ 30] men and women compared with men and women of normal BMI [&lt;25; RR, 2.08; 95% confidence interval (95% CI), 1.48-2.93, Ptrend = 0.0001]. After adjustment for between BMI, risk of pancreatic cancer was independently increased among men and women who reported a tendency for central weight gain compared with men and women reporting a tendency for peripheral weight gain (RR, 1.45; 95% CI, 1.02-2.07). We observed no difference in pancreatic cancer incidence rates between men and women who were most active (&gt;31.5 metabolic equivalent hours per week) at baseline compared with men and women who reported no recreational physical activity (RR, 1.20; 95% CI, 0.63-2.27).
Conclusion: This study, along with several recent studies, supports the hypothesis that obesity and central adiposity are associated with pancreatic cancer risk.
Analyzing Patterns of Staining in Immunohistochemical Studies: Application to a Study of Prostate Cancer Recurrence
Authors: Etzioni Ruth , Hawley Sarah , Billheimer Dean , True Lawrence D. , Knudsen Beatrice 
Published: September 2005

Abstract
Background: Immunohistochemical studies use antibodies to stain tissues with the goal of quantifying protein expression. However, protein expression is often heterogeneous resulting in variable degrees and patterns of staining. This problem is particularly acute in prostate cancer, where tumors are infiltrative and heterogeneous in nature. In this article, we introduce analytic approaches that explicitly consider both the frequency and intensity of tissue staining.
Methods: Compositional data analysis is a technique used to analyze vectors of unit-sum proportions, such as those obtained from soil sample studies or species abundance surveys. We summarized specimen staining patterns by the proportion of cells staining at mild, moderate, and intense levels and used compositional data analysis to summarize and compare the resulting staining profiles.
Results: In a study of Syndecan-1 staining patterns among 44 localized prostate cancer cases with Gleason score 7 disease, compositional data analysis did not detect a statistically significant difference between the staining patterns in recurrent (n = 22) versus nonrecurrent (n = 22) patients. Results indicated only modest increases in the proportion of cells staining at a moderate intensity in the recurrent group. In contrast, an analysis that compared quantitative scores across groups indicated a (borderline) significant increase in staining in the recurrent group (P = 0.05, t test).
Conclusions: Compositional data analysis offers a novel analytic approach for immunohistochemical studies, providing greater insight into differences in staining patterns between groups, but possibly lower statistical power than existing, score-based methods. When appropriate, we recommend conducting a compositional data analysis in addition to a standard score-based analysis.
Safety and Efficacy of Weekly Oral Oltipraz in Chronic Smokers
Authors: Kelley Michael J. , Glaser Elizabeth M. , Herndon James E. , Becker Frank , Bhagat Rajesh , Zhang Yu-Jing , Santella Regina M. , Carmella Steven G. , Hecht Stephen S. , Gallot Lilia , Schilder Lawrence , Crowell James A. , Perloff Marjorie , Folz Rodney J. , Bergan Raymond C. 
Published: September 2005

Abstract
Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo. Endobronchial tissue and bronchoalveolar lavage were done before and after 12 weeks of drug treatment; peripheral blood, urine, and oral saline rinse were also collected. Toxicity was assessed every 4 weeks. Fifty-nine of the 77 enrolled subjects completed the study. Of those receiving oltipraz, 15% experienced grade 2/3 toxicity, which was predominantly gastrointestinal. All subject withdrawals occurred in the oltipraz groups. There was no significant difference between pre- and post-polycyclic aromatic hydrocarbon-DNA adduct levels in lung epithelial cells measured by immunoperoxidase staining between treatment and placebo groups. Likewise, no significant differences were found in polycyclic aromatic hydrocarbon or benzo(a)pyrene-7,8-diol-9,10-epoxide adducts measured in blood, oral lining cells, or bladder lining cells. There was also no increase in mRNA or enzymatic activity of phase II enzymes and no change in glutathione levels. Thus, despite moderate drug-related toxicity, there was no significant effect on pharmacodynamic or surrogate risk biomarkers. Other agents with lower toxicity and greater activity to induce phase II enzymes are needed to definitively test the detoxification-induction paradigm in smokers.
TheMTHFR 1298A&gt;CPolymorphism and Genomic DNA Methylation in Human Lymphocytes
Authors: Friso Simonetta , Girelli Domenico , Trabetti Elisabetta , Olivieri Oliviero , Guarini Patrizia , Pignatti Pier Franco , Corrocher Roberto , Choi Sang-Woon 
Published: September 2005

AbstractMethylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both implicated in carcinogenesis. Epidemiologic studies have shown that two functional polymorphisms in MTHFR gene, 677C&gt;T and 1298A&gt;C, are related to increased cancer risk. We aimed to analyze lymphocyte DNA from 198 subjects to evaluate the MTHFR 1298A&gt;C polymorphism and folate status affecting genomic DNA methylation as a possible mechanism underlying the relationship between MTHFR polymorphisms and cancer susceptibility. Carriers of the 1298AA wild-type genotype showed lower genomic DNA methylation compared with 1298AC or 1298CC genotypes [3.72 versus 8.59 or 6.79 ng 5-methyl-2′-deoxycytidine (5-mCyt)/μg DNA, P &lt; 0.0001 and P = 0.007, respectively]. When DNA methylation was evaluated according to plasma folate status, only 1298AA with low folate levels revealed diminished DNA methylation (P &lt; 0.0001). Moreover, when the two MTHFR polymorphisms were concomitantly evaluated at the low folate status, DNA methylation was reduced only in 1298AA/677TT compared with 1298AA/677CC (3.11 versus 7.29 ng 5-mCyt/μg DNA, P = 0.001) and 1298CC/677CC genotypes (3.11 versus 7.14 ng 5-mCyt/μg DNA, P = 0.004). However, the high prevalence of 677TT mutants within the 1298AA group (79%) and the similar biochemical features of 1298AA/677CC and 1298CC/677CC combined genotypes suggest that the gene-nutrient interaction affecting DNA methylation in 1298AA is mainly due to the coexistence of the 677TT genotype and that the 1298A&gt;C polymorphism may convey its protective effect not through this interaction but through another pathway in one-carbon metabolism. Further mechanistic studies are warranted to investigate how single polymorphisms as well as MTHFR combined genotypes exert their effect on cancer susceptibility.
Maternal Diet and Infant Leukemia: The DNA Topoisomerase II Inhibitor Hypothesis: A Report from the Children's Oncology Group
Authors: Spector Logan G. , Xie Yang , Robison Leslie L. , Heerema Nyla A. , Hilden Joanne M. , Lange Beverly , Felix Carolyn A. , Davies Stella M. , Slavin Joanne , Potter John D. , Blair Cindy K. , Reaman Gregory H. , Ross Julie A. 
Published: September 2005

Abstract
Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+).
Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression.
Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL−).
Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.
Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women
Authors: Nagata Chisato , Nagao Yasuko , Shibuya Chiken , Kashiki Yoshitomo , Shimizu Hiroyuki 
Published: September 2005

Abstract
Background: Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer.
Methods: We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women.
Results: There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (≥3.00 μg/g creatinine) than in those with low urinary cadmium (&lt;2.00 μg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results.
Conclusion: Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.
MT1G Hypermethylation Is Associated with Higher Tumor Stage in Prostate Cancer
Authors: Henrique Rui , Jerónimo Carmen , Hoque Mohammad O. , Nomoto Shuji , Carvalho André L. , Costa Vera L. , Oliveira Jorge , Teixeira Manuel R. , Lopes Carlos , Sidransky David 
Published: September 2005

Abstract
Purpose: Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer.
Patients and Methods: The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment.
Results: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation.
Conclusions: Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.
A Prospective Study of C-Peptide, Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-1, and the Risk of Colorectal Cancer in Women
Authors: Wei Esther K. , Ma Jing , Pollak Michael N. , Rifai Nader , Fuchs Charles S. , Hankinson Susan E. , Giovannucci Edward 
Published: September 2005

Abstract
Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.
Physical Activity and Risk of Endometrial Cancer: A Report from the Shanghai Endometrial Cancer Study
Authors: Matthews Charles E. , Xu Wang Hong , Zheng Wei , Gao Yu Tang , Ruan Zhi Xian , Cheng Jia Rong , Xiang Yong Bing , Shu Xiao Ou 
Published: September 2005

Abstract
We evaluated the type and amount of physical activity associated with risk of endometrial cancer. In this population-based case-control study, in-person interviews were completed among 832 incident endometrial cancer cases and 846 age-matched controls. Physical activity from exercise, household activities, and transportation was assessed in adolescence and adulthood, as was lifetime occupational activity. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence limits (95% CL). Women reporting exercise participation in both adolescence and adulthood were at nearly a 40% reduced risk (OR, 0.63; 95% CL, 0.42-0.95), compared with women reporting no exercise in either life period. Postmenopausal women who initiated exercise in adulthood were also at reduced risk (OR, 0.76; 95% CL, 0.56-1.02). Reductions in risk were also observed for common lifestyle activities, including household activity (both life periods) and walking for transportation (adulthood). Examination of the independent and combined effect of exercise and lifestyle activities revealed that women with less active lifestyles but who reported exercise were at 35% reduced risk (OR, 0.65; 95% CL, 0.41-1.02), whereas nonexercisers with more active lifestyles were at 40% to 45% reduced risk. These findings suggest that both lifestyle activities of lower intensity (e.g., walking and doing household chores) and intentional exercise can reduce endometrial cancer risk.
Carcinogen Exposure during Short-term Switching from Regular to “Light” Cigarettes
Authors: Benowitz Neal L. , Jacob Peyton , Bernert John T. , Wilson Margaret , Wang Langing , Allen Faith , Dempsey Delia 
Published: September 2005

Abstract
Objectives: “Light” cigarettes are extremely popular and are perceived by many smokers as less hazardous than higher-yield cigarettes. The objectives of this study were (a) to assess a battery of biomarkers of tobacco smoke exposure that includes tobacco smoke carcinogens, (b) to examine the behavioral nature of compensation, and (c) to examine the consistency of an individual's tobacco smoke exposure when smoking the same cigarette at different times.
Methods: The study was a 3-week crossover study in which smokers smoked their usual cigarettes during weeks 1 and 3, and a light cigarette, with a machine-determined nicotine yield of about 50% of the usual cigarette, during week 2. Blood and urine biomarkers of exposure and subjective questionnaires were collected weekly.
Results: Based on cotinine and carboxyhemoglobin levels, compensation averaged 78% and 83%, respectively. Urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol, a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-butanone, and a number of polycyclic aromatic hydrocarbon metabolites was similar in all conditions. Compensation was accomplished both by smoking cigarettes more intensively and by smoking more cigarettes per day. Exposures to various tobacco smoke constituents while smoking the usual brand of cigarette in weeks 1 and 3 were highly correlated.
Conclusion: Our findings support the idea that smokers compensate to a high degree when switched from their usual brand to a light cigarette. Short-term switching resulted in no significant reduction in carcinogen exposure. Our assessment, based on measures of biochemical exposures, supports the idea that switching to light cigarettes is unlikely to reduce the health risks of cigarette smoking.
Evaluation of Risk Factors for Nasopharyngeal Carcinoma in High-Risk Nasopharyngeal Carcinoma Families in Taiwan
Authors: Yang Xiaohong (Rose) , Diehl Scott , Pfeiffer Ruth , Chen Chien-Jen , Hsu Wan-Lun , Dosemeci Mustafa , Cheng Yu-Juen , Sun Brenda , Goldstein Alisa M. , Hildesheim Allan ,   The Chinese and American Genetic Epidemiology of NPC Study Team
Published: September 2005

Abstract
A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the association between NPC and potential etiologic factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using conditional logistic regression, although these associations were not as strong as in the case-control study possibly due to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before age 10 was stronger in families with early NPC age-onset [odds ratio (ORwood), 5.10; 95% confidence interval (95% CI), 1.50-17.34; ORfish, 3.94; 95% CI, 1.47-10.55] or three or more affected members (ORwood, 4.41; 95% CI, 1.58-12.30; ORfish, 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families (OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased.
Interactions of Peroxisome Proliferator–Activated Receptor γ and Diet in Etiology of Colorectal Cancer
Authors: Murtaugh Maureen A. , Ma Khe-ni , Caan Bette J. , Sweeney Carol , Wolff Roger , Samowitz Wade S. , Potter John D. , Slattery Martha L. 
Published: September 2005

AbstractThe peroxisome proliferator–activated receptor γ (PPARγ) is one of a group of ligand-activated nuclear receptors responsible for regulation of glucose, lipid homeostasis, cell differentiation, and apoptosis. The 12 proline-to-alanine (Pro12Ala) substitution polymorphism in PPARγ produces proteins with lower activity. Variation in PPARγ expression in the bowel and the role of dietary fatty acids as ligands for PPARγ led investigation of whether the associations of diet with colon and rectal cancer risk were modified by PPARγ genotype. Data (diet, lifestyle, and DNA) came from case-control studies of colon (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake, dietary fiber, and calcium. We found no significant interactions between macronutrient (fat, protein, and carbohydrate) and colorectal cancer. High lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA PPARγ genotype were associated with reduced colon cancer risk. Risk of rectal cancer was increased among those with the PA/AA PPARγ genotype and a high mutagen index (OR, 1.63; 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for PPARγ is related to activation of PPARγ by nutrients or dietary patterns acting as ligands or direct influences of these nutrients on colon and rectal cancer processes that are important with lower PPARγ activity.