bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium
Authors: Miller Eric A. , Keku Temitope O. , Satia Jessie A. , Martin Christopher F. , Galanko Joeseph A. , Sandler Robert S. 
Published: September 2005

Abstract
Objective: Decreased apoptosis in the colon is potentially an early indicator of colon cancer risk and may be influenced by calcium and vitamin D. This report describes the associations of calcium intake and 25-hydroxyvitamin D levels with apoptosis in colorectal epithelium.
Methods: Consecutive patients undergoing colonoscopies were recruited for a study designed to examine risk and etiologic factors for colorectal adenomas. Diet was assessed by food frequency questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were measured using an enzyme immunoassay. Apoptosis was scored from normal rectal mucosal pinch biopsies. Linear and logistic regression analyses were used to examine associations between calcium, serum vitamin D, and apoptotic scores. Data were available for 498 and 280 patients for the calcium and vitamin D analyses, respectively.
Results: Associations of calcium intake and vitamin D with apoptosis were modified by adenoma case-status. In an adjusted logistic regression model, patients with adenomas in the highest versus lowest tertile of dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI), 0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the highest level of 25-hydroxyvitamin D was associated with higher apoptosis in adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2).
Conclusion: These results are consistent with a calcium and vitamin D-mediated apoptotic mechanism in colon carcinogenesis.
Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Cancer
Authors: Lindblad Mats , Lagergren Jesper , García Rodríguez Luis A. 
Published: September 2005

Abstract
Introduction: Nonsteroidal anti-inflammatory drugs (NSAID) might reduce risks of esophageal and gastric cancer, but previous studies are limited and provide somewhat conflicting results.
Methods: We tested these associations in a prospective, nested case-control study based on the General Practitioners Research Database, including over 2 million persons in the United Kingdom between 1994 and 2001. In multivariate analyses we calculated odds ratios (OR) with 95% confidence intervals (95% CI). Data were stratified by history of upper gastrointestinal (UGI) disorders and recalculated using 2 years lag time on data (i.e., excluding all information 2 years before index date).
Results: Among 4,340,207 person-years of follow-up, we identified 909 patients with esophageal cancer and 1,023 patients with gastric cancer. We randomly selected 10,000 control subjects. Overall analysis suggested that long-term users of nonaspirin NSAIDs were at reduced risks of esophageal (OR, 0.82; 95% CI, 0.57-1.18) and gastric cancer (OR, 0.65; 95% CI, 0.44-0.94), whereas long-term aspirin users might be at decreased risk of esophageal cancer (OR, 0.76; 95% CI, 0.53-1.08), but not of gastric cancer (OR, 1.09; 95% CI, 0.82-1.45). All estimates of reduced risk were weakened in the 2 years lag time analysis except the association between nonaspirin NSAIDs long-term users and gastric cancer. Potentially protective effects were suggestive of being more marked among subjects with a history of UGI disorders.
Conclusions: Nonaspirin NSAIDs long-term use was associated with a reduced risk of gastric cancer, whereas no other studied associations could be firmly established. Our results suggest that UGI disorders could distort the associations, although we could not show this with statistical significance. If such bias was to be true, the previously reported inverse associations might, at least partly, be explained by lack of appropriate adjustment for such disorders.
Influence of Type of Cigarette on Peripheral versus Central Lung Cancer
Authors: Brooks Daniel R. , Austin John H.M. , Heelan Robert T. , Ginsberg Michelle S. , Shin Victor , Olson Sara H. , Muscat Joshua E. , Stellman Steven D. 
Published: September 2005

AbstractObjectives: Adenocarcinoma has replaced squamous cell carcinoma as the most common cell type of lung cancer in the United States. It has been proposed that this shift is due to the increased use of filter and lower-tar cigarettes, resulting in increased delivery of smoke to peripheral regions of the lungs, where adenocarcinoma usually occurs. We reviewed radiologic data to evaluate the hypothesis that tumors in smokers of cigarettes with lower-tar yield are more likely to occur peripherally than tumors in smokers of higher-yield cigarettes.Methods: At two urban academic medical centers, we reviewed computed tomographic scans, chest radiographs, and medical records to assign tumor location (peripheral or central) for 330 smokers diagnosed with carcinoma of the lung between 1993 and 1999. We compared the proportion of tumors in a peripheral versus central location by lifetime filter use and average lifetime tar rating (&lt;21 and ≥21 mg).Results: Tumor location (69% peripheral and 31% central) was unrelated to cigarette filter use. Smokers of cigarettes with lower-tar ratings were more likely than those with higher ratings to have peripheral rather than central tumors (odds ratio, 1.76; 95% confidence interval, 0.89-3.47). When restricted to subjects with adenocarcinoma or squamous cell carcinoma, the odds ratio (95% confidence interval) was 2.31 (1.05-5.08).Conclusions: Among cigarette smokers with lung cancer, use of cigarettes with lower-tar yield was associated with preferential occurrence of tumors in peripheral sites. Our findings support the hypothesis that changes in smoking associated with lower-tar cigarettes have led to a shift in the location of smoking-related lung cancer.
Matrix Metalloproteinase-1 Promoter Polymorphism and Lung Cancer Risk
Authors: Su Li , Zhou Wei , Park Sohee , Wain John C. , Lynch Thomas J. , Liu Geoffrey , Christiani David C. 
Published: September 2005

Abstract
Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2G allele of the MMP-1 −1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% CI, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% CI, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males.
Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study
Authors: Satia Jessie A. , Keku Temitope , Galanko Joseph A. , Martin Christopher , Doctolero Ryan T. , Tajima Akihiro , Sandler Robert S. , Carethers John M. 
Published: September 2005

Abstract
Objective: Microsatellite instability (MSI) is one form of genomic instability that occurs in 10% to 20% of sporadic colon tumors and almost all hereditary nonpolyposis colon cancers. However, little is known about how environmental factors (e.g., diet) may influence MSI in sporadic colon cancer.
Methods: We used data from a population-based case-control study in North Carolina (486 colon cancer cases and 1,048 controls) to examine associations of diet (total energy, macronutrients, micronutrients, and food groups) with MSI. In-person interviews elicited information on potential colon cancer risk factors, and a previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year before diagnosis or interview date. MSI was classified as MSI-high (MSI-H) and MSI-low or microsatellite stable (MSI-L/MSS). Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (OR).
Results: Ten percent of the cases (n = 49) had MSI-H tumors (29% African American). The strongest associations between diet and MSI were observed in case-control comparisons: there was a robust inverse association between MSI-H status and β-carotene [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.9] and positive associations with energy-adjusted refined carbohydrates (OR, 2.2; 95% CI, 0.9-5.4) and non-energy-adjusted read meat intake (OR, 2.0; 95% CI, 0.9-4.2). Compared with controls, MSI-L/MSS tumors were statistically significantly associated with energy-adjusted vitamin C, vitamin E, calcium, dietary fiber, and dark green vegetables and positively associated with total energy intake (all Ps for trend &lt; 0.05). In case-case comparisons, no dietary factors were significantly differently related to MSI-H compared with MSI-L/MSS tumors.
Conclusion: Refined carbohydrate and red meat consumption may promote development of MSI-H tumors, whereas β-carotene may be associated with lower risk.
The Association of Measured Breast Tissue Characteristics with Mammographic Density and Other Risk Factors for Breast Cancer
Authors: Li Tong , Sun Limei , Miller Naomi , Nicklee Trudey , Woo Jennifer , Hulse-Smith Lee , Tsao Ming-Sound , Khokha Rama , Martin Lisa , Boyd Norman 
Published: September 2005

Abstract
Background: We have examined the relationships between the measured properties of breast tissue and mammographic density and other risk factors for breast cancer, using breast tissue obtained at forensic autopsy and not selected for the presence of abnormalities.
Methods: We used randomly selected tissue blocks taken from breast tissue slices obtained by s.c. mastectomy at the time of forensic autopsy to measure histologic features using quantitative microscopy. The proportions of the biopsy occupied by cells (estimated by nuclear area), glandular structures, and collagen were determined. These measurements were examined in relation to the percent density in the faxitron image of the tissue slice from which the biopsy was taken and other risk factors for breast cancer.
Results: The percent mammographic density was associated with the proportion of the area of the biopsy occupied by nuclei, both epithelial and nonepithelial, and by collagen and the area of glandular structures. Several other risk factors for breast cancer, notably body weight, parity, and number of births, and menopausal status, that are associated with variations in mammographic density, were also associated with differences in one or more of these tissue features.
Conclusion: All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for some risk factors, this influence includes an effect on the number of cells and the quantity of collagen.
Smoking Topography, Brand Switching, and Nicotine Delivery: Results from an In vivo Study
Authors: Hammond David , Fong Geoffrey T. , Cummings K. Michael , Hyland Andrew 
Published: September 2005

Abstract
Objective: Exposure to toxins in tobacco smoke is influenced by how a cigarette is smoked. Cigarettes have been designed to allow for a range of puffing behavior and to provide different, nonlinear tar and nicotine yields in response to different puffing profiles. However, puffing behavior and its influence upon risk-exposure has yet to be assessed outside the laboratory, in smokers' natural environment.
Method: Fifty-nine adult smokers used a portable device to measure smoking topography over the course of three 1-week trials. Participants were asked to smoke their usual “regular yield” brand through the device for trial 1 and again, 6 weeks later, at trial 2. Half the subjects were then randomly assigned to switch to a “low-yield” brand for trial 3.
Results: The findings show a high degree of stability in puffing behavior within the same subject over time but considerable variability between smokers. Smokers who were switched to a “low-yield” cigarette increased their total smoke intake per cigarette by 40% (P = 0.007), with no significant change in their salivary cotinine levels. Cigarettes smoked per day and nicotine yield were only weakly associated with salivary cotinine levels; however, salivary cotinine was strongly associated with a composite measure that included cigarettes per day, brand elasticity, and puffing behavior (sr = 0.61, P &lt; 0.001).
Conclusions: These findings provide strong evidence of behavioral compensation to low-yield cigarettes from in vivo measures of smoking behavior. The findings also show the importance of brand elasticity and smoking topography in predicting nicotine uptake and smoke exposure.
Polymorphisms ofMethionine SynthaseandMethionine Synthase Reductaseand Risk of Squamous Cell Carcinoma of the Head and Neck: a Case-Control Analysis
Authors: Zhang Zhengdong , Shi Qiuling , Liu Zhensheng , Sturgis Erich M. , Spitz Margaret R. , Wei Qingyi 
Published: September 2005

AbstractAlthough tobacco and alcohol use are the major risk factors, folate deficiency has been implicated in the risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that polymorphisms of methionine synthase (MTR) and methionine synthase reductase (MTRR) in the folate matabolic pathway are associated with SCCHN risk. In a hospital-based case-control study of 721 SCCHN cases and 1,234 controls of non-Hispanic Whites, frequency matched by age, sex, and smoking status, we genotyped the MTR A2756G and MTRR G66A polymorphisms. We found that the MTR variant AG and AG/GG genotypes were associated with a significantly increased SCCHN risk [adjusted odd ratio (OR), 1.31; 95% confidence interval (95% CI), 1.07-1.60 for AG and OR, 1.28; 95% CI, 1.05-1.56 for AG/GG] compared with the AA genotype. In contrast, the MTRR variant AA genotype was associated with a significantly decreased SCCHN risk (OR, 0.68; 95% CI, 0.52-0.90) compared with the 66GG genotype. When the two polymorphisms were evaluated together by the number of risk alleles, the SCCHN risk was significantly increased in a dose-dependent manner (Ptrend = 0.002). The risk of SCCHN was 1.47 (95% CI, 1.08-1.99) for one risk allele, 1.67 (95% CI, 1.23-2.27) for two risk alleles, and 1.74 (95% CI, 1.18-2.54) for three or four risk alleles compared with the wild-type (0 risk allele) genotype. In conclusion, our data provide evidence that support the association between the MTR A2756G and MTRR G66A polymorphisms and SCCHN risk and that these two polymorphisms may have a joint effect on risk of SCCHN.
A Digital Image Analysis System for Identifying Filter Vent Blocking on Ultralight Cigarettes
Authors: O'Connor Richard J. , Stitt Joseph P. , Kozlowski Lynn T. 
Published: September 2005

Abstract
Filter ventilation is the dominant design feature on modern cigarettes, diluting the mainstream smoke with air and reducing tar and nicotine yields in the standard assay. Smokers are generally unaware of vent holes and often cover them with lips or fingers while smoking, reducing or eliminating the air dilution effect and increasing intake of tar and nicotine particularly on ultra–low tar brands. A digital imaging and analysis system for the detection of vent blocking was developed. Two studies were designed to evaluate the effectiveness of three color measures (hue, saturation, and value) at discriminating whether at least 50% blocking had occurred. In study 1, saturation showed perfect discrimination between unblocked Carlton butts and butts with at least 50% of the vents blocked during syringe smoking. In study 2, saturation showed 95% accuracy at identifying Marlboro Ultra Light butts with at least four puffs blocked by smokers' lips. The results indicate that the pattern of color saturation is related to vent blocking. Implications for tobacco control research and policy are discussed.
Frequent Methylation ofEyes Absent 4Gene in Barrett's Esophagus and Esophageal Adenocarcinoma
Authors: Zou Hongzhi , Osborn Neal K. , Harrington Jonathan J. , Klatt Kristie K. , Molina Julian R. , Burgart Lawrence J. , Ahlquist David A. 
Published: September 2005

AbstractMost esophageal adenocarcinomas arise within Barrett's esophagus but the cause of this increasingly prevalent condition remains unknown. Early detection improves survival and discriminant screening markers for Barrett's esophagus and cancer are needed. This study was designed to explore the natural history of eyes absent 4 (EYA4) gene methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated EYA4 as a candidate marker. Aberrant promoter methylation of EYA4 was studied by methylation-specific PCR using bisulfite-treated DNA from esophageal adenocarcinomas, Barrett's esophagus, and normal epithelia, and then confirmed by sequencing. Eight cancer cell lines were treated with the demethylation agent 5-aza-2′-deoxycytidine, and EYA4 mRNA expression with and without treatment was quantified by real-time reverse-transcription PCR. EYA4 hypermethylation was detected in 83% (33 of 40) of esophageal adenocarcinomas and 77% (27 of 35) of Barrett's tissues, but only in 3% (2 of 58) of normal esophageal and gastric mucosa samples (P &lt; 0.001). The unmethylated cancer cell lines had much higher EYA4 mRNA expression than the methylated cancer cell lines. Demethylation caused by 5-aza-2′-deoxycytidine increased the mRNA expression level by a median of 3.2-fold in methylated cells, but its effect on unmethylated cells was negligible. Results indicate that aberrant promoter methylation of EYA4 is very common during tumorigenesis in Barrett's esophagus, occurs in early metaplasia, seems to be an important mechanism of down-regulating EYA4 expression, and represents an intriguing candidate marker for Barrett's metaplasia and esophageal cancer.
SerumTrans-Fatty Acids Are Associated with Risk of Prostate Cancer in β-Carotene and Retinol Efficacy Trial
Authors: King Irena B. , Kristal Alan R. , Schaffer Steve , Thornquist Mark , Goodman Gary E. 
Published: September 2005

AbstractBiomarkers of trans-fatty acid consumption have been associated with increased risks of breast and colon cancer, although no studies have examined their associations with prostate cancer risk. Using data from the β-Carotene and Retinol Efficacy Trial, this nested case-control study examined the relationships between serum phospholipid trans-fatty acids and prostate cancer incidence in 272 case and 426 control men. Trans-fatty acids were measured using organic extraction followed by separations with TLC and gas chromatography. Adjusted odds ratios for risk of prostate cancer with increasing levels of trans-fatty acids were calculated using logistic regression. There were consistent trends for increasing prostate cancer risk with higher levels of C18 but not C16 trans-fatty acids, although only trends for Δ11t 18:1 trans-vaccenic and Δ9c,12t 18:2 fatty acids reached statistical significance. Odds ratios (95% confidence interval) contrasting low versus high quartiles for these fatty acids were 1.69 (1.03-2.77) and 1.79 (1.02-3.15), respectively. There were no consistent differences in associations between low-grade and high-grade cancer among the subset of 209 cases with information on tumor grade. Additional studies are needed to confirm these findings and better control for factors, such as use of prostate-specific antigen screening, which may confound this association.
Nonsteroidal Anti-inflammatory Drugs and Risk of Prostate Cancer in the Baltimore Longitudinal Study of Aging
Authors: Platz Elizabeth A. , Rohrmann Sabine , Pearson Jay D. , Corrada Maria M. , Watson Douglas J. , De Marzo Angelo M. , Landis Patricia K. , Metter E. Jeffrey , Carter H. Ballentine 
Published: September 2005

AbstractBackground: Laboratory and epidemiologic studies suggest that aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAID) reduce the risk of cancer, possibly via inhibition of the cyclooxygenase enzymes. We evaluated the association of aspirin and nonaspirin NSAIDs with subsequent prostate cancer in a prospective study. We also assessed whether use of these drugs influences serum prostate-specific antigen (PSA) concentration.Methods: Participants were 1,244 male members of the Baltimore Longitudinal Study of Aging. Use of prescription and over-the-counter drugs was collected by questionnaire and interview at multiple study visits. One hundred forty-one prostate cancer cases diagnosed between 1980 and May 2004 were confirmed by medical record review. We used Cox proportional hazards regression to estimate the rate ratio (RR) of prostate cancer updating drug use over time and taking into account age and year. We used generalized estimating equations to calculate age-adjusted geometric mean PSA concentration by aspirin or nonaspirin NSAIDs use among 933 of the men without prostate cancer, for whom 3,749 PSA measurements in archived sera had been done previously.Results: On 46.0% and 21.5% of the visits, current use of aspirin or nonaspirin NSAIDs (mostly ibuprofen) was reported, respectively. The RRs of prostate cancer comparing ever to never use were 0.76 [95% confidence interval (95% CI), 0.54-1.07] for aspirin, 0.79 (95% CI, 0.54-1.16) for nonaspirin NSAIDs, and 0.71 (95% CI, 0.49-1.02) for either medication. The association for ever use of either aspirin or nonaspirin NSAIDs was suggestively more pronounced in men &lt;70 years (RR, 0.54; 95% CI, 0.27-1.03) than in men ≥70 years (RR, 0.78; 95% CI, 0.50-1.22; Pinteraction = 0.73). The RR for current use of either drug was attenuated relative to ever use. Mean PSA concentration did not differ between users and nonusers of either aspirin or nonaspirin NSAIDs (1.01 versus 0.98 ng/mL, P = 0.56).Conclusion: In this prospective study, men, in particular younger men, who had ever used aspirin or nonaspirin NSAIDs had a modest nonstatistically significant lower risk of prostate cancer. The modest inverse association was unlikely due to detection bias that might have resulted if anti-inflammatory drugs had influenced serum PSA concentration.