bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoking Is a Risk Factor for Cervical Intraepithelial Neoplasia Grade 3 among Oncogenic Human Papillomavirus DNA–Positive Women with Equivocal or Mildly Abnormal Cytology
Authors: McIntyre-Seltman Kathleen , Castle Philip E. , Guido Richard , Schiffman Mark , Wheeler Cosette M. ,   for The ALTS Group
Published: September 2005

Abstract
Background: Smoking is a potential risk factor for cervical cancer and its immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3), but few studies have adequately taken into account the possible confounding effect of oncogenic human papillomavirus (HPV) infection.
Methods: Women (n = 5,060) with minimally abnormal Papanicolaou smears were enrolled in the ASCUS and LSIL Triage Study, a clinical trial to evaluate management strategies, and were seen every 6 months for the 2-year duration of the study. Cervical specimens were tested for HPV DNA using both Hybrid Capture 2 and PGMY09/11 L1 consensus primer PCR with reverse line blot hybridization for genotyping. Multivariate logistics regression models were used to assess associations [odds ratio (OR) with 95% confidence intervals (95% CI)] between smoking behaviors and rigorously reviewed cases of cervical intraepithelial neoplasia grade 3 or cancer (≥CIN3) identified throughout the study (n = 506) in women with oncogenic HPV (n = 3,133).
Results: Current smoking was only weakly associated with increased HPV infection. Among infected women, current smokers (OR, 1.7; 95% CI, 1.4-2.1) and past smokers (OR, 1.7; 95% CI, 1.2-2.4) were more likely to be diagnosed with ≥CIN3 than nonsmokers. Greater smoking intensity (PTrend &lt; 0.0005) and duration (PTrend &lt; 0.0005) increased the strength of the association, with smoking ≥2 packs/d (OR, 3.3; 95% CI, 1.5-7.5) and smoking for ≥11 years (OR, 2.1; 95% CI, 1.5-2.9) most strongly associated with ≥CIN3 as compared to non-smokers. The effects of intensity and duration seemed additive.
Conclusions: Women with oncogenic HPV and minimally abnormal Papanicolaou smears who smoke were up to three times more likely to be diagnosed with ≥CIN3 than nonsmokers. Smoking cessation trials targeting this population might be warranted.
The Effect of Over-the-Counter Sales of the Nicotine Patch and Nicotine Gum on Smoking Cessation in California
Authors: Reed Mark B. , Anderson Christy M. , Vaughn Jerry W. , Burns David M. 
Published: September 2005

Abstract
The Food and Drug Administration approved over-the-counter (OTC) sale of nicotine gum and nicotine patches in 1996. We used data from the 1996 California Tobacco Survey to compare the rates of nicotine replacement therapy (NRT) use and smoking abstinence in California for each month during a period immediately preceding and immediately following the OTC availability of nicotine gum and patches. For smokers eligible to report a quit attempt, the proportion making a quit attempt using NRT and the proportion remaining abstinent was calculated for each of the 12 months prior to the survey interview. Multiple regression modeling of quit attempts and abstinence included a term for the number of months between the quit attempt and survey interview and dummy variables for the months before and after the OTC availability of NRT. Results showed a significant increase in the fraction of smokers using the patch (P &lt; 0.01) and gum (P &lt; 0.05) immediately following their availability OTC. There was also a significantly higher proportion of smokers reporting abstinence with gum use (P &lt; 0.01) and a significant increase in reported abstinence with patch use (P &lt; 0.01) during the period of time immediately following the availability of these products without a prescription. The results of this study suggest that removing the prescription status of NRT products resulted in an immediate increase in quit attempts and smoking abstinence with the use of nicotine gum or patches.
Urinary Hydroxyestrogens and Breast Cancer Risk among Postmenopausal Women: A Prospective Study
Authors: Wellejus Anja , Olsen Anja , Tjonneland Anne , Thomsen Birthe L. , Overvad Kim , Loft Steffen 
Published: September 2005

Abstract
Background: It has been suggested that a low level of the 2-hydroxyestrogen metabolites (2-OHE) and a high level of 16α-hydroxyestrone (16α-OHE1) are associated with an enhanced risk of breast cancer. We examined the association between the metabolite levels and breast cancer in a nested case-control study, which also addressed hormone replacement therapy (HRT) and estrogen receptor status of the tumors.
Methods: 24,697 postmenopausal Danish women were enrolled in the “Diet, Cancer and Health” cohort. During follow-up, 426 breast cancer cases were identified and controls were matched by age at diagnosis, baseline age, and HRT use. The concentrations of 2-OHE and 16α-OHE1 in spot urine were measured by an enzyme immunoassay. Incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated for total and estrogen receptor–specific breast cancer and were stratified according to HRT use.
Results: A higher incidence of estrogen receptor–positive breast cancer with an enhanced 2-OHE level was observed among current HRT users, IRR per doubling = 1.30 (95% CI, 1.02-1.66), whereas no association was seen among nonusers of HRT, IRR per doubling = 1.00 (95% CI, 0.69-1.45). The association between estrogen receptor–positive breast cancer and the 16α-OHE1 metabolite level was in the opposite direction but slightly weaker and statistically insignificant. For estrogen receptor–negative breast cancer, no significant associations were seen.
Conclusions: The risk of breast cancer, in particular the estrogen receptor–positive type, was enhanced among postmenopausal women using estradiol-based HRT and among those who had a high 2-OHE concentration.
Common Leptin Receptor Polymorphisms do not Modify the Effect of Alcohol Ingestion on Serum Leptin Levels in a Controlled Feeding and Alcohol Ingestion Study
Authors: Roth Mark J. , Paltoo Dina N. , Albert Paul S. , Baer David J. , Judd Joseph T. , Tangrea Joseph , Taylor Philip R. 
Published: September 2005

Abstract
We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P ≥ 0.26).
The Molecular Signature of Normal Squamous Esophageal Epithelium Identifies the Presence of a Field Effect and Can Discriminate between Patients with Barrett's Esophagus and Patients with Barrett's-Associated Adenocarcinoma
Authors: Brabender Jan , Marjoram Paul , Lord Reginald V.N. , Metzger Ralf , Salonga Dennis , Vallböhmer Daniel , Schäfer Hartmut , Danenberg Kathleen D. , Danenberg Peter V. , Selaru Florin M. , Baldus Stefan E. , Hölscher Arnulf H. , Meltzer Stephen J. , Schneider Paul M. 
Published: September 2005

Abstract
Background and Aim: Genetic alterations in the normal tissues surrounding various cancers have been described, but a comprehensive analysis of this carcinogenic field effect in Barrett's-associated adenocarcinoma of the esophagus disease has not been reported. The aim of this study was to analyze the gene expression profile of a panel of highly selected genes in the normal squamous esophagus epihelium of patients with Barrett's esophagus, patients with Barrett's-associated adenocarcinoma, and a healthy control group to define the existence of a carcinogenic field effect, and to investigate the clinical importance of such a field effect in the management of Barrett's disease.
Methods: Forty-nine histologic normal squamous esophageal epithelia collected from 19 patients with Barrett's esophagus, 20 patients with Barrett's-associated esophageal adenocarcinoma, and a healthy control group of 10 patients were studied. A quantitative real-time reverse transcription-PCR method (TaqMan) was used to measure the expression of a panel of genes with known associations with gastrointestinal carcinogenesis.
Results: A widespread carcinogenic field effect was detected for more than 50% of the genes analyzed including Bax, BFT, CDX2, COX2, DAPK, DNMT1, GSTP1, RARα, RARγ, RXRα, RXRβ, SPARC, TSPAN, and VEGF. Based on the expression signature of the normal appearing squamous esophagus, a linear discriminant analysis was able to distinguish between the three groups of patients with an error rate of 0%.
Conclusion: This study provides the first comprehensive investigation of a carcinogenic field effect in Barrett's esophagus disease. Based on the gene expression signature of the normal esophagus, patients could be correctly characterized according to their pathologic classification by applying a linear discriminant analysis. Our results provide evidence that a molecular classification might have clinical importance for the diagnosis and treatment of patients with Barrett's esophagus disease.
Serum Concentrations of Estrogens, Sex Hormone Binding Globulin, and Androgens and Risk of Breast Hyperplasia in Postmenopausal Women
Authors: Schairer Catherine , Hill Deirdre , Sturgeon Susan R. , Fears Thomas , Mies Carolyn , Ziegler Regina G. , Hoover Robert N. , Sherman Mark E. 
Published: September 2005

Abstract
Objective: We sought to determine whether serum concentrations of estrogens, androgens, and sex hormone binding globulin in postmenopausal women were related to the presence of mammary hyperplasia, an established breast cancer risk factor.
Methods: Study participants provided serum before breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977 and 1987. A total of 179 subjects with breast hyperplasia were compared with 152 subjects with nonproliferative breast changes that are not associated with increased breast cancer risk.
Results: The odds ratios (OR) associated with the three upper quartiles of estradiol in comparison with the lowest quartile were 2.2 [95% confidence interval (95% CI) 1.1-4.6], 2.5 (95% CI, 1.1-5.3), and 4.1 (95% CI, 2.0-8.5; Ptrend = 0.007). The corresponding ORs for bioavailable estradiol, estrone, and estrone sulfate were of generally similar magnitude (Ptrend = 0.003 for bioavailable estradiol, 0.0004 for estrone, and 0.0009 for estrone sulfate). Relative to women concurrently in the lowest tertile for serum estradiol, estrone, and estrone sulfate, women concurrently in the highest tertile for all three hormones had an OR of 5.8 (95% CI, 2.2-15.2). Serum concentrations of sex hormone binding globulin, testosterone, dehydroepiandrosterone, androstenedione, and androstenediol were not associated with risk of hyperplasia.
Conclusions: Serum concentrations of estrogens, but not of androgens or sex hormone binding globulin, were strongly and significantly associated with risk of breast hyperplasia in postmenopausal women, suggesting that estrogens are important early in the pathologic process towards breast cancer.
Statins and Cancer Development
Authors: Duncan Robin E. , El-Sohemy Ahmed , Archer Michael C. 
Published: September 2005

Abstract
There is epidemiologic evidence that the hydrophilic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor pravastatin increases the incidence of some extrahepatic cancers, although this finding has been attributed to chance. We hypothesize that pravastatin is able to promote the development of cancer by causing an induction of HMG-CoA reductase and, hence, mevalonate synthesis in extrahepatic tissues. We have shown that mevalonate, the product of HMG-CoA reductase, promotes the growth of breast cancer cells. Because there is no uptake of pravastatin by most extrahepatic cells, this statin will be unable to mitigate the increase in mevalonate synthesis in extrahepatic tissues that accompanies the decrease in circulating cholesterol caused by its inhibition of hepatic HMG-CoA reductase.
Etiology of Gastric Cancer: What Is New?
Authors: Correa Pelayo , Schneider Barbara G. 
Published: September 2005

Abstract
Recent advances in understanding of risk factors for gastric cancer have focused attention on genetic polymorphisms in both the human host and in Helicobacter pylori. Variation in genes for cytokines such as interleukin-1β and its receptor antagonist may allow identification of those individuals predisposed to mount an immune response that puts them at elevated risk for gastric cancer. Likewise, analysis of how genetic variation in the genome of H. pylori may modulate the action of virulence factors like CagA may prove useful in identification of persons for whom H. pylori eradication efforts would be most important. This review examines recent studies on interleukin-1β polymorphisms and H. pylori CagA variation with respect to their modulation of risk for gastric cancer.
Aspirin Use and Risk of Biliary Tract Cancer: A Population-Based Study in Shanghai, China
Authors: Liu Enju , Sakoda Lori C. , Gao Yu-Tang , Rashid Asif , Shen Ming-Chang , Wang Bing-Sheng , Deng Jie , Han Tian-Quan , Zhang Bai-He , Fraumeni Joseph F. , Hsing Ann W. 
Published: September 2005

Abstract
The association of gallbladder and bile duct cancers with gallstones, cholecystitis, and cholangitis suggest that chronic inflammation contributes to the carcinogenic process. However, the effect of nonsteroidal anti-inflammatory drugs, such as aspirin, on biliary tract cancer has not been well studied. In a population-based case-control study conducted in Shanghai, China, we examined the relationship between aspirin use and the risk of biliary disease. A total of 627 patients with biliary tract cancer, including cancers of the gallbladder (n = 368), extrahepatic bile duct (n = 191), and ampulla of Vater (n = 68); 1,037 patients with biliary stones; and 958 healthy adults were included in the study. Self-reported data on aspirin use was collected from study participants by in-person interview. The prevalence of aspirin use was low, with 5.7% of the population controls being regular users. After controlling for age, sex, education, and biliary stone status, aspirin use was associated with a reduced risk of gallbladder cancer [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.17-0.88]. An inverse relationship was also observed for frequency and duration of use and with younger age when starting use. In addition, there was a nonsignificant reduction in the risk of bile duct (OR, 0.48; 95% CI, 0.19-1.19) and ampullary cancers (OR, 0.22; 95% CI, 0.03-1.65) associated with aspirin use, whereas no clear association was seen with biliary stones (OR, 0.92; 95% CI, 0.59-1.44). Further studies of biliary tract cancer in other populations are needed to confirm these results and to elucidate the mechanisms that underlie the reduced risk associated with use of aspirin and possibly other nonsteroidal anti-inflammatory drugs.
GSTM1, GSTT1, andGSTP1Polymorphisms and Risk of Advanced Colorectal Adenoma
Authors: Moore Lee E. , Huang Wen-Yi , Chatterjee Nilanjan , Gunter Marc , Chanock Stephen , Yeager Meredith , Welch Bob , Pinsky Paul , Weissfeld Joel , Hayes Richard B. 
Published: September 2005

AbstractCigarette smoking is a risk factor for colon adenoma. The glutathione S-transferase enzymes are involved in the detoxification of carcinogenic compounds including those found in tobacco smoke, and thus, may be important modifiers of individual risk of developing this disease. We examined the prevalence of GSTM1 and GSTT1 gene deletions, and two GSTP1 polymorphisms in 772 cases with advanced colorectal adenomas (&gt;1 cm, villous elements or high-grade dysplasia) of the distal colon (descending or sigmoid colon or rectum) and 777 sigmoidoscopy negative controls enrolled in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Epidemiologic data on smoking was collected by self-administered questionnaire and DNA was extracted from whole blood or buffy coat. For GSTM1 and GSTT1, we used a newly developed TaqMan-based assay capable of discriminating heterozygous (+/−) individuals from those with two active alleles (+/+) and homozygous deletions (−/−). For GSTP1, the I105V and the A114V substitutions were identified using end point 5′ nuclease assays (TaqMan). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were determined using unconditional logistic regression, controlling for age, race, and gender. Advanced adenoma risk was increased in current/former smokers (OR, 1.4; 95% CI, 1.2-1.8). Risks were decreased in subjects with ≥1 inactive GSTM1 alleles (OR, 0.6; 95% CI, 0.4-0.9); and the association was independent of smoking status (P interaction = 0.59). Having ≥1 inactive GSTT1 allele was associated with increased risk among smokers (OR, 1.4; 95% CI, 1.1-1.9; Ptrend = 0.02) but not among never smokers (OR, 0.9; 95% CI, 0.6-1.3) and a significant interaction between smoking and genotype was observed (P interaction = 0.05). In summary, this is the first study to report associations between colorectal adenomas and GSTM1 wild-type and GSTT1 null allele among smokers. These findings only became apparent using a newly developed assay able to distinguish heterozygous from wild-type individuals. Our data provide evidence that phenotypic differences between these two groups exist.
Fruits, Vegetables, and Antioxidants and Risk of Gastric Cancer among Male Smokers
Authors: Nouraie Mehdi , Pietinen Pirjo , Kamangar Farin , Dawsey Sanford M. , Abnet Christian C. , Albanes Demetrius , Virtamo Jarmo , Taylor Philip R. 
Published: September 2005

Abstract
The effect of consumption of fruits, vegetables, and antioxidants on the incidence of gastric cancer is inconclusive. In this prospective cohort study, we report the association of dietary intake of fruits, vegetables, antioxidants, and baseline serum levels of antioxidants with subsequent incidence of gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Participants of this study were 29,133 male smokers recruited into the α-Tocopherol, β-Carotene Cancer Prevention study between 1985 and 1988. At baseline, a self-administered food use questionnaire with 276 food items was used to assess dietary intake. Baseline serum samples were stored at −70°C. During a median follow-up of 12 years, 243 incident gastric adenocarcinomas (64 GCC and 179 GNCC) were diagnosed in this cohort, of whom 220 (57 GCC and 163 GNCC) had complete dietary information. For GCC, high dietary intake of retinol was protective [hazard ratio (HR), 0.46; 95% confidence interval (95% CI), 0.27-0.78], but high intake of α-tocopherol (HR, 2.06; 95% CI, 1.20-3.54) and γ-tocopherol (HR, 1.94; 95% CI, 1.13-3.34) increased risk. For GNCC, higher intakes of fruits (HR, 0.51; 95% CI, 0.37-0.71), vitamin C (HR, 0.60; 95% CI, 0.41-0.86), α-tocopherol (HR, 0.78; 95% CI, 0.55-1.10), γ-tocopherol (HR, 0.69; 95% CI, 0.49-0.96), and lycopene (HR, 0.67; 95% CI, 0.47-0.95) were protective. Our results suggest a difference in the effect of some of these exposures on GCC and GNCC. Tocopherols were associated with higher risk of GCC, whereas dietary intake of fruits, vitamin C, tocopherols, and lycopene seemed protective for GNCC.
Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism and Breast Cancer Risk
Authors: González-Zuloeta Ladd Angela M. , Arias Vásquez Alejandro , Sayed-Tabatabaei Fakhredin A. , Coebergh J.W. , Hofman Albert , Njajou Omer , Stricker Bruno , van Duijn Cornelia 
Published: September 2005

Abstract
Background: The renin-angiotensin system plays an important role in homeostasis and lately, its main effector, angiotensin II, has been attributed with angiogenic and growth factor actions in the breast tissue. Previous studies have shown that the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for the variability of ACE plasma concentrations. The use of ACE inhibitors and the ACE I/D polymorphism may be linked to breast cancer risk. In this study, we evaluate the relationship of the ACE I/D polymorphism with breast cancer risk in Caucasian postmenopausal women.
Methods: The ACE I/D polymorphism was genotyped in 4,117 women participants in the Rotterdam Study. Baseline information was obtained through a questionnaire. We conducted a logistic regression and survival analysis to assess the risk of breast cancer by the ACE genotype.
Results: The DD carriers showed a significantly increased risk of developing breast cancer when compared with the II carriers (odds ratio, 1.86; 95% confidence interval, 1.06-3.27; P = 0.03). This association remained after adjusting for other risk factors, including body mass index, age at menarche, age at menopause, hormone replacement therapy, and hypertension. Our survival analysis showed that the cancer-free survival was significantly reduced in DD compared with II carriers (hazard ratio, 1.80; 95% confidence interval, 1.07-3.01; P = 0.03).
Conclusions: Our results suggest that the ACE I/D polymorphism plays an important role in breast cancer risk and disease-free survival in Caucasian postmenopausal women.
Menstrual Cycle Characteristics and Incidence of Premenopausal Breast Cancer
Authors: Terry Kathryn L. , Willett Walter C. , Rich-Edwards Janet W. , Hunter David J. , Michels Karin B. 
Published: September 2005

Abstract
Background: Epidemiologic studies have indicated that menstrual cycle characteristics such as age at menarche and age at menopause are associated with breast cancer risk. Anovulation, which is more common with long or irregular cycles, has been hypothesized to reduce the incidence of breast cancer.
Methods: We analyzed data from the Nurses' Health Study II, a cohort of 116,671 female registered nurses ages 25 to 42 years at baseline. Information on menstrual cycle characteristics was assessed in 1989 and 1993, and incident cases of premenopausal breast cancer were ascertained through 2001.
Results: During 1,135,496 person-years of follow-up (1989-2001), 1,163 incident cases of invasive premenopausal breast cancer were diagnosed. Overall, women with long menstrual cycles at ages 18 to 22 years (&gt;32 days or too irregular to estimate) did not experience a significantly lower breast cancer risk compared with women with normal cycle lengths (26-31 days) at that age [covariate-adjusted hazard ratio (HR), 0.92; 95% confidence interval (95% CI), 0.79-1.06]. Among women ages &lt;40 years, those with menstrual cycles lasting &gt;32 days or too irregular to estimate at ages 18 to 22 years had a decreased incidence of breast cancer (covariate-adjusted HR, 0.71; 95% CI, 0.53-0.97). Current menstrual cycle characteristics were not associated with breast cancer incidence.
Conclusion: Overall, longer or irregular cycles at ages 18 to 22 years or in early adulthood were not associated with reduced premenopausal breast cancer risk. However, longer menstrual cycles at ages 18 to 22 years were associated with a lower incidence of premenopausal breast cancer before age 40.