bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA Content Increase in Response to Cigarette Smoking
Authors: Masayesva Brett G. , Mambo Elizabeth , Taylor Rodney J. , Goloubeva Olga G. , Zhou Shaoyu , Cohen Yoram , Minhas Khalid , Koch Wayne , Sciubba James , Alberg Anthony J. , Sidransky David , Califano Joseph 
Published: March 2006

Abstract
An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy. Total DNA was extracted from exfoliated cells in saliva. DNA from a nuclear gene, β-actin, and two mitochondrial genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real-time PCR. mtDNA content was correlated with age, exposure history, and other variables using multivariate regression analyses. A significant increase (P &lt; 0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I and Cox II, respectively) and former smokers (31% and 34%) when compared with never smokers. This association persisted after adjustment for other significant factors including age, alcohol drinking, and income (P &lt; 0.001). Increased mtDNA content was positively associated with pack-years of smoking (P = 0.02). Despite an average smoking cessation interval of 21 years in former smokers, tobacco cessation interval was not statistically significantly associated with mtDNA content. Smoking is associated with increased mtDNA content in a dose-dependent fashion. Mitochondrial DNA alterations in response to smoking persist for several decades after smoking cessation, consistent with long-term, smoking-related damage. (Cancer Epidemiol Biomarkers Prev 2006;15(1):19–24)
Breast Cancer Screening, Outside the Population-Screening Program, of Women from Breast Cancer Families without Proven BRCA1/BRCA2 Mutations: a Simulation Study
Authors: Jacobi Catharina E. , Nagelkerke Nico J.D. , van Houwelingen J. (Hans) C. , de Bock Geertruida H. 
Published: March 2006

Abstract
Purpose: We assessed the cost-effectiveness of mammography screening for women under the age of 50, from breast cancer families without proven BRCA1/BRCA2 mutations, because current criteria for screening healthy women from breast cancer families are not evidence-based.
Methods: We did simulation studies with mathematical models on the cost-effectiveness of mammography screening of women under the age of 50 with breast cancer family histories. Breast cancer screening was simulated with varying screening intervals (6, 12, 18, and 24 months) and screening cohorts (starting at ages 30, 35, 40, and 45, and continuing to age 50). Incremental costs of screening were compared with those of women ages 50 to 52 years, the youngest age group currently routinely screened in the nationwide screening program of the Netherlands, to determine cost-effectiveness. Sensitivity analyses were done to explore the effects of model assumptions. The cost-effectiveness of breast cancer screening for women over the age of 50 was not debated.
Results: The most effective screening interval was found to be 12 months, which, however, seems only to be cost-effective in a small group of women under the age of 50 with at least two affected relatives, including at least one affected in the first degree diagnosed under the age of 50. Significantly, early breast cancer screening never seemed to be cost-effective in women with only one affected first-degree or second-degree relative.
Conclusion: Annual breast cancer screening with mammography for women under the age of 50 seems to be cost-effective in women with strong family histories of breast cancer, even when no BRCA1/BRCA2 mutation was found in affected family members. (Cancer Epidemiol Biomarkers Prev 2006;15(3):429–36)
Eliminating Carcinogenic Acetaldehyde By Cysteine From Saliva During Smoking
Authors: Salaspuro Ville J. , Hietala Jaana M. , Marvola Martti L. , Salaspuro Mikko P. 
Published: March 2006

Abstract
Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity. We developed a tablet that releases cysteine into the oral cavity during smoking and could therefore be a potential chemopreventive agent against toxicity of tobacco smoke. In this study, the efficacy of l-cysteine–containing tablets to reduce the carcinogenic acetaldehyde in the saliva during tobacco smoking was examined. Seven volunteers smoked five cigarettes. During every smoking period, each volunteer sucked a blinded tablet containing 0, 1.25, 2.5, 5, or 10 mg of l-cysteine. Acetaldehyde was analyzed from salivary samples gas chromatographically at 0, 5, and 10 minutes from the beginning of the smoking. All tablets containing l-cysteine reduced highly significantly the salivary acetaldehyde; 5 mg of l-cysteine was the minimum concentration to totally eliminate the acetaldehyde from saliva. The mean salivary acetaldehyde concentrations in samples collected immediately after smoking with 0, 1.25, 2.5, 5, or 10 mg of l-cysteine were 228 ± 115 μmol/L, 85 ± 42 μmol/L (P = 0.007), 9 ± 7 μmol/L, 0.09 ± 0.2 μmol/L, 0 ± 0 μmol/L (P &lt; 0.001), respectively. In conclusion, carcinogenic acetaldehyde could be totally inactivated in the saliva during smoking by sucking tablet containing 5 mg of l-cysteine. Even a small reduction of the carcinogenicity of cigarette smoke could gain benefit at the population level. Hence, this finding warrants for further clinical trials for l-cysteine tablet in the prevention of upper digestive tract cancers in smokers. (Cancer Epidemiol Biomarkers Prev 2006;15(1):146–9)
Endocrine Biomarkers in Ductal Lavage Samples from Women at High Risk for Breast Cancer
Authors: Bhandare Deepa , Nayar Ritu , Bryk Michele , Hou Nanjiang , Cohn Rachel , Golewale Nazar , Parker Noah P. , Chatterton Robert T. , Rademaker Alfred , Khan Seema A. 
Published: March 2006

AbstractBackground: Ductal lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting.Methods: Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) α, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The ductal lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF).Results: One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low (P for interaction = 0.001).Conclusions: Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.
Toenail Arsenic Concentrations, GSTT1 Gene Polymorphisms, and Arsenic Exposure from Drinking Water
Authors: Kile Molly L. , Houseman E. Andres , Rodrigues Ema , Smith Thomas J. , Quamruzzaman Quazi , Rahman Mahmuder , Mahiuddin Golam , Su Li , Christiani David C. 
Published: March 2006

Abstract
Toenail arsenic (As) concentrations were evaluated as a biomarker of inorganic As (Asin) exposure in a population residing in an As-endemic region of Bangladesh. Drinking water and toenail samples were collected from 48 families (n = 223) every 3 months for 2 years and analyzed for As using inductively coupled plasma-mass spectrometry. Drinking water collected 3, 6, and 9 months before each toenail sample collection was combined into a weighted lagged exposure variable. The contribution of each water sample to the measured toenail As concentration was estimated using maximum likelihood that accounted for fluctuations in drinking water exposure and toenail growth. The best model attributed 69%, 14%, and 17% of the toenail As content to drinking water exposures that occurred 3, 6, and 9 months before toenail collection [95% confidence intervals (95% CI), 0.46-0.97, 0.00-0.31, and 0.03-0.35, respectively]. Generalized additive mixed models using penalized regression splines were employed to model the data. Below a drinking water concentration of 2 μg As/L, no relationship between drinking water As and toenail As concentrations was observed. Above this concentration, toenail As content increased in a dose-dependent fashion as drinking water As increased. Age was a significant effect modifier of drinking water As exposure on toenail As (β = 0.01; 95% CI, 0.002-0.02). Individuals possessing GSTT1-null genotypes had significantly more As in their toenails in contrast to GSTT1 wild-type individuals (β = 0.11; 95% CI, 0.06-0.2). Therefore, it seems that GSTT1 modifies the relationship between Asin exposure and toenail Asin content.
Regional Differences in Breast Cancer Survival Despite Common Guidelines
Authors: Eaker Sonja , Dickman Paul W. , Hellström Vivan , Zack Matthew M. , Ahlgren Johan , Holmberg Lars ,   the Uppsala/Örebro Breast Cancer Group
Published: March 2006

Abstract
Purpose: Despite a uniform regional breast cancer care program, breast cancer survival differs within regions. We therefore examined breast cancer survival in relation to differences in diagnostic activity, tumor characteristics, and treatment in seven Swedish counties within a single health care region.
Methods: We conducted a population-based observational study using a clinical breast cancer register in one Swedish health care region. Eligible women (n = 7,656) ages 40 to 69 years diagnosed with primary breast cancer between 1992 and 2002 were followed up until 2003. The 7-year relative survival ratio was used to estimate breast cancer survival. Excess mortality was modeled using Poisson regression to study differences in survival between counties.
Results: The 7-year relative survival for breast cancer patients was significantly lower (up to 7% in absolute risk difference) in one county (county A) compared with the others. This difference existed only among women diagnosed before 1998, ages 50 to 59 years, and was strongest among stage II breast cancer patients. Adjustment for amount of diagnostic activity eliminated the survival differences among the counties. The amount of diagnostic activity was also lower in county A during the same time period. After county A, during 1997-1998, began to adhere strictly to the regional breast cancer care program, neither any survival differences nor diagnostic activity differences were observed.
Interpretations: Markers of diagnostic activity explained survival differences within our region, and the underlying mechanisms may be several. Low diagnostic activity may entail later diagnosis or inadequate characterization of the tumor and thereby missed treatment opportunities. Strengthening of multidisciplinary management of breast cancer can improve survival. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2914–8)
Interleukin-8Promoter Polymorphism Increases the Risk of Atrophic Gastritis and Gastric Cancer in Japan
Authors: Taguchi Ayumu , Ohmiya Naoki , Shirai Kennosuke , Mabuchi Nobuyuki , Itoh Akihiro , Hirooka Yoshiki , Niwa Yasumasa , Goto Hidemi 
Published: March 2006

AbstractHost genetic susceptibility may influence gastric carcinogenesis caused by Helicobacter pylori infection. We aimed to clarify the relationship of interleukin (IL)-8 polymorphism with the risk of atrophic gastritis and gastric cancer. We examined IL-8 −251 T &gt; A, IL-1B −511 C &gt; T, and IL-1RN intron 2 polymorphisms in 252 healthy controls, 215 individuals with atrophic gastritis, and 396 patients with gastric cancer. We also investigated the effect of the IL-8 polymorphism on IL-8 production and histologic degree of gastritis in noncancerous gastric mucosa. Although no correlation was found in the analysis of the IL-1B and IL-1RN polymorphisms, IL-8 −251 A/A genotype held a higher risk of atrophic gastritis [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.12-4.94] and gastric cancer (OR, 2.22; 95% CI, 1.08-4.56) compared with the T/T genotype. We also found that the A/A genotype increased the risk of upper-third location (OR, 3.66; 95% CI, 1.46-9.17), diffuse (OR, 2.79; 95% CI, 1.21-6.39), poorly differentiated (OR, 2.70; 95% CI, 1.14-6.38), lymph node (OR, 2.50; 95% CI, 1.01-6.20), and liver metastasis (OR, 5.63; 95% CI, 1.06-30.04), and p53-mutated (OR, 1.91; 95% CI, 1.13-3.26) subtypes of gastric cancer. The A/A and A/T genotypes were significantly associated with higher levels of IL-8 protein compared with the T/T genotype. Neutrophil infiltration score was significantly higher in the A/A genotype than in the T/T genotype. In conclusion, we showed that the IL-8 −251 T &gt; A polymorphism is associated with higher expression of IL-8 protein, more severe neutrophil infiltration, and increased risk of atrophic gastritis and gastric cancer.
Polymorphisms and Haplotypes in the Cytochrome P450 17A1, Prolactin, and Catechol-O-Methyltransferase Genes and Non-Hodgkin Lymphoma Risk
Authors: Skibola Christine F. , Bracci Paige M. , Paynter Randi A. , Forrest Matthew S. , Agana Luz , Woodage Trevor , Guegler Karl , Smith Martyn T. , Holly Elizabeth A. 
Published: March 2006

Abstract
Expression of prolactin and of prolactin and estrogen receptors in lymphocytes, bone marrow, and lymphoma cell lines suggests that hormonal modulation may influence lymphoma risk. Prolactin and estrogen promote the proliferation and survival of B cells, factors that may increase non-Hodgkin lymphoma risk, and effects of estrogen may be modified by catechol-O-methyltransferase (COMT), an enzyme that alters estrogenic activity. Cytochrome P450 17A1 (CYP17A1), a key enzyme in estrogen biosynthesis, has been associated with increased cancer risk and may affect lymphoma susceptibility. We studied the polymorphisms prolactin (PRL) −1149G&gt;T, CYP17A1 −34T&gt;C, and COMT 108/158Val&gt;Met, and predicted haplotypes among a subset of participants (n = 308 cases, n = 684 controls) in a San Francisco Bay Area population-based non-Hodgkin lymphoma study (n = 1,593 cases, n = 2,515 controls) conducted from 1988 to 1995. Oral contraceptive and other hormone use also was analyzed. Odds ratios (OR) for non-Hodgkin lymphoma and follicular lymphoma were reduced for carriers of the PRL −1149TT genotype [OR, 0.64; 95% confidence interval (95% CI), 0.41-1.0; OR, 0.53; 95% CI, 0.26-1.0, respectively]. Diffuse large-cell lymphoma risk was increased for those with CYP17A1 polymorphisms including CYP17A1 −34CC (OR, 2.0; 95% CI, 1.1-3.5). ORs for all non-Hodgkin lymphoma and follicular lymphoma among women were decreased for COMT IVS1 701A&gt;G [rs737865; variant allele: OR, 0.53; 95% CI, 0.34-0.82; OR, 0.42; 95% CI, 0.23-0.78, respectively]. Compared with never users of oral contraceptives, a 35% reduced risk was observed among oral contraceptive users in the total population. Reduced ORs for all non-Hodgkin lymphoma were observed with use of exogenous estrogens among genotyped women although 95% CIs included unity. These results suggest that PRL, CYP17A1, and COMT may be relevant genetic loci for non-Hodgkin lymphoma and indicate a possible role for prolactin and estrogen in lymphoma pathogenesis.
Effects of Glucosinolate-Rich Broccoli Sprouts on Urinary Levels of Aflatoxin-DNA Adducts and Phenanthrene Tetraols in a Randomized Clinical Trial in He Zuo Township, Qidong, People's Republic of China
Authors: Kensler Thomas W. , Chen Jian-Guo , Egner Patricia A. , Fahey Jed W. , Jacobson Lisa P. , Stephenson Katherine K. , Ye Lingxiang , Coady Jamie L. , Wang Jin-Bing , Wu Yan , Sun Yan , Zhang Qi-Nan , Zhang Bao-Chu , Zhu Yuan-Rong , Qian Geng-Sun , Carmella Stephen G. , Hecht Stephen S. , Benning Lorie , Gange Stephen J. , Groopman John D. , Talalay Paul 
Published: March 2006

AbstractResidents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing either 400 or &lt;3 μmol glucoraphanin nightly for 2 weeks. Adherence to the study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin-N7-guanine were not different between the two intervention arms (P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and showed a robust inverse association with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed (P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions.
Interactions among Smoking, Obesity, and Symptoms of Acid Reflux in Barrett's Esophagus
Authors: Smith Kylie J. , O'Brien Suzanne M. , Smithers B. Mark , Gotley David C. , Webb Penelope M. , Green Adèle C. , Whiteman David C. ,   for the Study of Digestive Health
Published: March 2006

Abstract
Background: Barrett's esophagus, a metaplastic precursor to esophageal adenocarcinoma, is becoming increasingly prevalent in many populations. Clinical studies suggest acid reflux causes Barrett's esophagus; however, no population-based estimates of risk have been reported, and the role of other health factors in modifying risk is unclear.
Methods: We conducted a population-based case-control study in Brisbane, Australia. Cases were 167 patients with histologically confirmed Barrett's esophagus diagnosed between February and December 2003. Age-matched and sex-matched controls (n = 261) were randomly selected from a population register. Data on exposure to self-reported symptoms of acid reflux, smoking, obesity, and other factors were collected through self-completed questionnaires followed by telephone interview. Risks of Barrett's esophagus and Barrett's esophagus with dysplasia associated with these exposures were estimated by the odds ratio (OR) and 95% confidence interval (95% CI), both crude and adjusted for other factors.
Results: Self-reported weekly episodes of acid reflux were associated with greatly increased risks of Barrett's esophagus (adjusted OR, 29.7; 95% CI, 12.2-72.6) and Barrett's esophagus with dysplasia (OR, 59.7; 95% CI, 18.5-193). Smoking was also associated with risk of Barrett's esophagus. We found evidence of interactions between symptoms of acid reflux and smoking and obesity. Obese people with self-reported symptoms of acid reflux had markedly higher risks of Barrett's esophagus (OR, 34.4; 95% CI, 6.3-188) than people with reflux alone (OR, 9.3; 95% CI, 1.4-62.2) or obesity alone (OR, 0.7; 95% CI, 0.2-2.4). Similarly, those reporting both acid reflux symptoms and smoking were at substantially higher risks of Barrett's esophagus (OR, 51.4; 95% CI, 14.1-188) than those reporting acid reflux or smoking alone.
Conclusions: Although history of symptoms of acid reflux is the principle factor associated with Barrett's esophagus, risks are substantially increased by obesity and smoking.
Longitudinal Study of Urinary Phenanthrene Metabolite Ratios: Effect of Smoking on the Diol Epoxide Pathway
Authors: Hecht Stephen S. , Chen Menglan , Yoder Andrea , Jensen Joni , Hatsukami Dorothy , Le Chap , Carmella Steven G. 
Published: March 2006

AbstractWe have proposed that urinary phenanthrene metabolites could be used in a carcinogen metabolite phenotyping approach to identify individuals who may be susceptible to cancer induction by polycyclic aromatic hydrocarbons (PAH). In support of this proposal, we have developed methods for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and phenanthrols (HOPhe) in human urine. PheT is the end product of the diol epoxide metabolic activation pathway of PAH, whereas HOPhe are considered as detoxification products. In this study, we investigated the longitudinal consistency of these metabolites over time in smokers and nonsmokers and compared their levels. Twelve smokers and 10 nonsmokers provided urine samples daily for 7 days, then weekly for 6 weeks. Levels of PheT, HOPhe, and PheT/HOPhe ratios were relatively constant in most individuals, with mean coefficients of variation ranging from 29.3% to 45.7%. There were no significant changes over time in levels of the metabolites or in ratios. These results indicate that a single urine sample should be sufficient when comparing phenanthrene metabolites in different groups. PheT/HOPhe ratios were significantly higher in smokers than in nonsmokers, showing that smoking induces the diol epoxide metabolic activation pathway of phenanthrene. This finding is consistent with previous studies indicating that inducibility of PAH metabolism contributes to cancer risk in smokers. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2969–74)