bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSD17B1 Genetic Variants and Hormone Receptor–Defined Breast Cancer
Authors: Gaudet Mia M. , Chanock Stephen , Dunning Alison , Driver Kristy , Brinton Louise A. , Lissowska Jolanta , Peplonska Beata , Pharoah Paul , Garcia-Closas Montserrat 
Published: October 2008

Abstract
HSD17B1 is an important candidate gene in breast cancer via its role in converting estrone to estradiol. A nonsynonymous G-to-A transition (rs605059) and an intronic C-to-A (rs676387) single-nucleotide polymorphism, which captured most common variation in HSD17B1, were evaluated in several breast cancer studies with inconclusive results. We followed up these findings in the Polish Breast Cancer Study (1,995 cases; 2,296 controls) and the British Studies of Epidemiology and Risk Factors in Cancer Heredity study (4,470 cases; 4,560 controls). Meta-analyses of published data and our own were also conducted among Caucasian women. Consistent with previous reports, we found little to no association with overall risk for heterozygotes and minor allele homozygotes compared with major allele homozygotes for rs605059 [summary odds ratios (95% confidence intervals), 0.93 (0.87-0.99) for GA and 0.96 (0.85-1.08), based on 11,762 cases and 14,329 controls from 10 studies] and for rs676387 [summary odds ratios (95% confidence intervals), 1.04 (0.97-1.12) and 1.12 (0.99-1.27), based on analyses of 11,074 cases and 13,605 controls from 8 studies]. Data from the Polish [n = 586 estrogen receptor–negative (ER-) cases] and British (n = 407) studies did not support the previous findings that ER- tumors were inversely associated with rs676387 AA genotype and positively associated with rs605059 GG genotype, based on subanalyses in 5 prospective cohorts with 354 ER- cases. In conclusion, it is unlikely that common genetic variation in HSD17B1 is associated with a moderate modulation in breast cancer risk overall; however, we cannot exclude the possibility of a very weak effect. Associations between HSD17B1 genotypes and risk for ER- breast cancer were inconsistent across studies and should be studied further. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2766–72)
Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers
Authors: Qiu Yu-lan , Wang Wei , Wang Tong , Liu Jing , Sun Pin , Qian Ji , Jin Li , Xia Zhao-lin 
Published: October 2008

Abstract
This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH2 = CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by real-time PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P = 0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2578–84)
Physical Activity, White Blood Cell Count, and Lung Cancer Risk in a Prospective Cohort Study
Authors: Sprague Brian L. , Trentham-Dietz Amy , Klein Barbara E.K. , Klein Ronald , Cruickshanks Karen J. , Lee Kristine E. , Hampton John M. 
Published: October 2008

AbstractPrevious studies have suggested that physical activity may lower lung cancer risk. The association of physical activity with reduced chronic inflammation provides a potential mechanism, yet few studies have directly related inflammatory markers to cancer incidence. The relation among physical activity, inflammation, and lung cancer risk was evaluated in a prospective cohort of 4,831 subjects, 43 to 86 years of age, in Beaver Dam, Wisconsin. A total physical activity index was created by summing up kilocalories per week from sweat-inducing physical activities, city blocks walked, and flights of stairs climbed. Two inflammatory markers, WBC count and serum albumin, were measured at the baseline examination. During an average of 12.8 years of follow-up, 134 incident cases of lung cancer were diagnosed. After multivariable adjustment, participants in the highest tertile of total physical activity index had a 45% reduction in lung cancer risk compared with those in the lowest tertile (hazard ratio, 0.55; 95% confidence interval, 0.35-0.86). Participants with WBC counts in the upper tertile (≥8 × 103/μL) were 2.81 (95% confidence interval, 1.58-5.01) times as likely to develop lung cancer as those with counts in the lowest tertile (&lt;6.4 × 103/μL). Serum albumin was not related to lung cancer risk. There was no evidence that inflammation mediated the association between physical activity and lung cancer risk, as the physical activity risk estimates were essentially unchanged after adjustment for WBC count. Although the potential for residual confounding by smoking could not be eliminated, these data suggest that physical activity and WBC count are independent risk factors for lung cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2714–22)
Progestagens Use Before Menopause and Breast Cancer Risk According to Histology and Hormone Receptors
Authors: Fabre Alban , Fournier Agnès , Mesrine Sylvie , Gompel Anne , Desreux Joëlle , Berrino Franco , Boutron-Ruault Marie-Christine , Romieu Isabelle , Clavel-Chapelon Françoise 
Published: October 2008

AbstractIn a previous study, we found a positive association between premenopausal use of progestagens and breast cancer risk. We conducted the present study to assess the risk of breast cancers defined by their histology and hormone receptors status. We evaluated the association between progestagen-only intake (except for mini pills) before menopause and after the age of 40 years and invasive breast cancer risk in 67,057 women participating in the French E3N cohort study. Histologically confirmed invasive breast cancers (2,264) were identified through biennial self-administered questionnaires completed from 1992 to 2002. Risk estimates were calculated using the Cox proportional hazard model. We found an increased risk of lobular carcinoma associated with premenopausal use of progestagens among both current and past users [hazard raatio (HR), 1.51; 95% confidence interval (95% CI), 1.02-2.24 and HR, 1.38; 95% CI, 1.08-1.75, respectively]. Among current users, the use of progestagens for 4.5 years or more was associated with an increased risk of estrogen receptor–positive/progesterone receptor–positive carcinomas (HR, 1.68; 95% CI, 1.05-2.68), whereas current use of progestagens for &lt;4.5 years was associated with an increase in the estrogen receptor–positive/progesterone receptor–negative carcinoma risk (HR, 1.61; 95% CI, 1.05-2.46). The premenopausal use of progestagens after the age of 40 years may be preferentially associated with the risk of lobular breast cancer and differentially affect the risk of breast cancer according to the hormone receptor status. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2723–8)
Increased Risk for Second Primary Malignancies in Women with Breast Cancer Diagnosed at Young Age: A Population-Based Study in Taiwan
Authors: Lee Kuan-Der , Chen Shin-Cheh , Chan Chunghuang Hubert , Lu Chang-Hsien , Chen Chih-Cheng , Lin Jen-Tsun , Chen Miao-Fen , Huang Shih-Hao , Yeh Chun-Ming , Chen Min-Chi 
Published: October 2008

Abstract
Studies conducted in Western countries have reported excess risks for second primary malignancies after breast cancer. However, there is little documentation of ethnic differences in these excess risks. Asian women are characterized by younger age at diagnosis of breast cancer, but very few reports are available on the incidences and risks for second primary cancers in this region. Using population-based data from the Taiwan National Cancer Registry (TNCR) for the period 1979 to 2003, we quantified standardized incidence ratios and cumulative incidence of second cancers among 53,783 women with initial diagnoses of breast cancer. Age-specific incidences showed peaks among women in their 40s, and 1,085 cases (2.02%) developed nonbreast second primary cancers. The risk for second cancers differs significantly according to age at diagnosis of breast cancer. In comparison with women diagnosed when ≥50 years (standardized incidence ratio, 0.96; 95% confidence interval; 0.89-1.04), there were significantly greater risks for bone, corpus uterine, ovarian, thyroid, esophageal, kidney and lung cancers, nonmelanoma skin cancer, and leukemia or lymphoma in women diagnosed when &lt;50 years (standardized incidence ratio, 1.43; 95% confidence interval, 1.29-1.58). The survival probabilities differed between breast cancer patients with and without second cancers (P &lt; 0.001). After diagnosis of the second cancer, the median survival time was only 2.87 years. In conclusion, we confirmed that young age at diagnosis of breast cancer predicted a subsequently increased risk for second malignancies, and the second cancers indeed worsen survivorship in patients who survived breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2647–55)
LINE-1 Hypomethylation Is Associated with Increased CpG Island Methylation in Helicobacter pylori–Related Enlarged-Fold Gastritis
Authors: Yamamoto Eiichiro , Toyota Minoru , Suzuki Hiromu , Kondo Yutaka , Sanomura Tamana , Murayama Yoko , Ohe-Toyota Mutsumi , Maruyama Reo , Nojima Masanori , Ashida Masami , Fujii Kyoko , Sasaki Yasushi , Hayashi Norio , Mori Mitsuru , Imai Kohzoh , Tokino Takashi , Shinomura Yasuhisa 
Published: October 2008

Abstract
Background: The molecular mechanism by which Helicobacter pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlarged-fold (EF+) gastritis, one cause of which is H. pylori infection, have an increased risk for gastric cancer, although again molecular mechanism is unclear. In the present study, we analyzed the methylation status of long interspersed nucleotide elements (LINE-1) and three cancer-related genes in a panel of gastric mucosae, with or without EF+ gastritis.
Methods: We used bisulfite pyrosequencing to assess the levels of LINE-1, CDH1, CDH13, and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients.
Results: Levels of LINE-1 methylation were significantly reduced in mucosae from patients with EF+ gastritis. This hypomethylation of LINE-1 was associated with increased methylation of the 5′ CpG islands of the genes, which suggests that, in EF+ gastritis, the methylation of the promoter regions of certain genes is accompanied by global demethylation of repetitive sequences.
Conclusions: Our results indicate that genomewide hypomethylation and regional hypermethylation occur in EF+ gastritis and may contribute to the tumorigenesis of diffuse-type gastric cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2555–64)
Methionine-Dependence Phenotype in the de novo Pathway in BRCA1 and BRCA2 Mutation Carriers with and without Breast Cancer
Authors: Beetstra Sasja , Suthers Graeme , Dhillon Varinderpal , Salisbury Carolyn , Turner Julie , Altree Meryl , McKinnon Ross , Fenech Michael 
Published: October 2008

Abstract
Methionine-dependence phenotype (MDP) refers to the reduced ability of cells to proliferate when methionine is restricted and/or replaced by its immediate precursor homocysteine. MDP is a characteristic of human tumors in vivo, human tumor cell lines, and normal somatic tissue in some individuals. It was hypothesized that MDP is a risk factor for developing breast cancer in BRCA (BRCA1 and BRCA2) germline mutation carriers. To test the hypothesis, human peripheral blood lymphocytes of BRCA carriers with and without breast cancer and healthy non-carrier relatives (controls) were cultured for 9 days in medium containing either 0.1 mmol/L l-methionine or 0.2 mmol/L d,l-homocysteine, with the ratio of viable cell growth in both types of medium after 9 days used to calculate the methionine-dependence index (MDI), a measure of MDP. We also tested whether MDP was associated with common polymorphisms in methionine metabolism. Viable cell growth, MDI, and polymorphism frequency in MTRR (A66G and C524T) and MTHFR (A1298C and A1793G) did not differ among the study groups; however, MDI tended to be higher in BRCA carriers with breast cancer than those without and was significantly increased in MTHFR 677T allele carriers relative to wild-type carriers (P = 0.017). The presence of MTR A2756G mutant allele and MTHFR C677T mutant allele in carriers was associated with increased breast cancer risk [odds ration, 3.2 (P = 0.16; 95% confidence interval, 0.76-13.9) and 3.9 (P = 0.09; 95% confidence interval, 0.93-16.3), respectively]. The results of this study support the hypothesis that defects in methionine metabolism may be associated with breast cancer risk in BRCA carriers. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2565–71)
Physical Activity during Pregnancy and Age at Menarche of the Daughter
Authors: Colbert Lisa H. , Graubard Barry I. , Michels Karin B. , Willett Walter C. , Forman Michele R. 
Published: October 2008

Abstract
In utero exposures have been proposed as possible determinants of later disease risk. Given that a later age at menarche is a breast cancer risk factor, and that higher childhood physical activity has been associated with a later menarcheal age, it is possible that a pregnant mother's activity may also influence this outcome. The purpose of this study was to determine if a mother's physical activity during pregnancy is related to their daughter's menarcheal age. Participants of the Nurses' Health Study II reported their age at menarche to the nearest year, whereas their mothers (n = 33,016) completed surveys regarding their health and lifestyle habits during their pregnancy with their daughters. Mothers reported their home, occupational, and leisure-time physical activities, as well as the activity of their daughters at ages 5 to 10 years. Using multiple linear regression analysis with adjustment for specific covariates including daughter's childhood body size, neither home nor occupational activity alone were associated with age at menarche of the daughter, but there was a direct association with leisure-time physical activity (Ptrend &lt; 0.001). Compared with women inactive in their leisure-time, women who were highly active had daughters with menarche 1.1 (95% confidence interval, 0.3-1.9) months later. Using a composite variable of both home and leisure-time activity, daughters of women who were highly active at home and in their leisure-time had daughters with menarche 3.1 (95% confidence interval, 0.4-5.9) months later than those who were highly inactive in both. Physical activity during pregnancy may be associated with a modest delay in menarcheal age in offspring. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2656–62)
Explaining the Race Difference in Prostate Cancer Stage at Diagnosis
Authors: Jones Beth A. , Liu Wen-Liang , Araujo Andre B. , Kasl Stanislav V. , Silvera Stephanie N. , Soler-Vilá Hosanna , Curnen Mary G.M. , Dubrow Robert 
Published: October 2008

Abstract
Prostate cancer is the most frequently diagnosed cancer in males in the United States, accounting for an estimated 186,320 new cases in 2008. There are striking racial or ethnic differences in prostate cancer incidence and mortality rates in the United States, with Black males 1.6 times more likely to be diagnosed and 2.4 times more likely to die with prostate cancer than Whites. Stage at diagnosis is a key prognostic factor for prostate cancer survival, with African-Americans generally diagnosed at a more advanced stage. To identify factors that explain the race-stage disparity in prostate cancer, we conducted a population-based case-case study of 251 African-American (46%) and White (54%) prostate cancer cases diagnosed in Connecticut between January 1987 and October 1990. Multivariate logistic regression was used to identify potential explanatory factors, including clinical, sociodemographic, medical care, insurance, digital rectal examination screening history, and lifestyle factors. Cox proportional hazards models assessed the impact of study variables on race differences in long-term survival. Modifiable factors such as screening practice and sociodemographic factors accounted for &gt;60% of the race difference in prostate cancer stage at diagnosis. Histologic grade (Gleason score) accounted for comparatively less. Survival analyses confirmed the importance of tumor characteristics, education, and insurance in explaining observed race differences in survival. Although cases were identified before the widespread use of prostate-specific antigen (PSA) screening, the results should also be relevant to countries that have large underserved populations and/or disparities in access to medical care and cancer screening. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2825–34)
Diagnostic mRNA Expression Patterns of Inflamed, Benign, and Malignant Colorectal Biopsy Specimen and their Correlation with Peripheral Blood Results
Authors: Galamb Orsolya , Sipos Ferenc , Solymosi Norbert , Spisák Sándor , Krenács Tibor , Tóth Kinga , Tulassay Zsolt , Molnár Béla 
Published: October 2008

AbstractPurpose: Gene expression profile (GEP)–based classification of colonic diseases is a new method for diagnostic purposes. Our aim was to develop diagnostic mRNA expression patterns that may establish the basis of a new molecular biological diagnostic method.Experimental Design: Total RNA was extracted, amplified, and biotinylated from frozen colonic biopsies of patients with colorectal cancer (n = 22), adenoma (n = 20), hyperplastic polyp (n = 11), inflammatory bowel disease (n = 21), and healthy normal controls (n = 11), as well as peripheral blood samples of 19 colorectal cancer and 11 healthy patients. Genome-wide gene expression profile was evaluated by HGU133plus2 microarrays. To identify the differentially expressed features, the significance analysis of microarrays and, for classification, the prediction analysis of microarrays were used. Expression patterns were validated by real-time PCR. Tissue microarray immunohistochemistries were done on tissue samples of 121 patients.Results: Adenoma samples could be distinguished from hyperplastic polyps by the expression levels of nine genes including ATP-binding cassette family A, member 8, insulin-like growth factor 1 and glucagon (sensitivity, 100%; specificity, 90.91%). Between low-grade and high-grade dysplastic adenomas, 65 classifier probesets such as aquaporin 1, CXCL10, and APOD (90.91/100) were identified; between colorectal cancer and adenoma, 61 classifier probesets including axin 2, von Willebrand factor, tensin 1, and gremlin 1 (90.91/100) were identified. Early- and advanced-stage colorectal carcinomas could be distinguished using 34 discriminatory transcripts (100/66.67).Conclusions: Whole genomic microarray analysis using routine biopsy samples is suitable for the identification of discriminative signatures for differential diagnostic purposes. Our results may be the basis for new GEP-based diagnostic methods. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2835–45)
Cigarette Smoking and Risk of Lung Metastasis from Esophageal Cancer
Authors: Abrams Julian A. , Lee Paul C. , Port Jeffrey L. , Altorki Nasser K. , Neugut Alfred I. 
Published: October 2008

Abstract
Background: Whereas extensive research has explored the effect of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer.
Methods: We conducted a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases. Information was gathered from medical records on smoking history, imaging results, site(s) of metastasis, and other patient and tumor characteristics. We used logistic regression to assess association.
Results: We identified 354 esophageal cancer cases; smoking status was known in 289 (82%). Among patients with lung metastases, 73.6% (39 of 53) were ever smokers, versus 47.8% (144 of 301) of patients without lung metastases [P = 0.001; summary odds ratio (OR), 2.52; 95% confidence interval (95% CI), 1.17-5.45; stratified by histology]. Smoking was associated with a nonsignificant increased adjusted odds of lung metastasis (OR, 1.89; 95% CI, 0.80-4.46). Upper esophageal subsite (OR, 4.71; 95% CI, 1.20-18.5), but not histology (squamous OR 0.65,95% CI 0.27-1.60), was associated with lung metastasis. Compared with the combined never/unknown smoking status group, smoking was associated with a significantly increased odds of lung metastasis (OR, 2.35; 95% CI, 1.11-4.97). There was no association between liver metastasis and smoking (OR, 0.88; 95% CI, 0.42-1.83).
Conclusions: Smoking is associated with increased odds of lung metastasis from esophageal cancer, and this relationship seems to be site specific. Future studies are needed to determine whether smoking affects the tumor cell or the site of metastasis, and whether this changes the survival outcome. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2707–13)