bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Adenomas: Pathological Differential Diagnosis with Malignant Tumors
Authors: Algaba F.
Published: October 2008

The renal adenomas can be confused by imaging diagnosis with malignant renal tumors, but there are also real biological dilemmas to determine their behavior. The consensus decisions are the following. (1) The adenoma of clear cells is not accepted, instead it is considered that all the clear-cell tumors are carcinomas, with greater or lesser aggressiveness. (2) Among the papillary neoplasms the WHO 2004 renal cell tumors classification are considered as papillary adenomas tumors with a maximum diameter of 5 mm and may represent a continuum biological process to papillary renal cell carcinoma. The papillary adenomas associated with End-kidney and/or acquired cystic disease may have a different pathogenesis. (3) To consider a tumor as an oncocytoma the size is not important, only the cytological features, microscopic, ultrastructural, and immunohistochemically can help, but some chromosomal observations introduce some questions about its relation with the chromophobe renal cell carcinoma. (4) Finally, the metanephric adenoma, a tumor with some morphological similarity with the nephroblastoma must be considered in the renal adenomas diagnosis.
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

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

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

Previous 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 (<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

In 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 <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

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 <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 < 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

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

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

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 < 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

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 >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

Purpose: 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

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)
Past Oral Contraceptive Use and Current Dietary Soy Isoflavones Influence Estrogen Metabolism in Postmenopausal Monkeys (Macaca fascicularis)
Authors: Scott Latanya M. , Xu Xia , Veenstra Timothy D. , Tooze Janet A. , Wood Charles E. , Register Thomas C. , Kock Nancy D. , Cline J. Mark
Published: October 2008

Estrogen metabolism may play an important role in mammary carcinogenesis in postmenopausal women. We evaluated the effects of prior oral contraceptive (OC) treatment and current soy isoflavone consumption on endogenous estrogen metabolite concentration and biomarkers of tissue estrogen exposure in a monkey model. One hundred eighty-one female cynomolgus macaques were randomized to receive OC or placebo for 26 months premenopausally, then ovariectomized and randomized to one of three diets for 36 months: an isoflavone-depleted soy protein isolate (Soy−) diet, a diet containing soy protein isolate with a human equivalent of 129 mg isoflavone/d (Soy+), or a Soy− diet supplemented with conjugated equine estrogens (CEE+) at a human equivalent dose of 0.625 mg/d. Reverse-phase high-performance liquid chromatography directly coupled with tandem mass spectrometry was used to measure the concentrations of estrogen species in urine samples. Generally, prior OC treatment was associated with significantly reduced urinary estrogen metabolites (25-55% reduction; P < 0.05 for each versus OC−). Animals that consumed isoflavones postmenopausally had increased urinary 2-hydroxyestrone and 16α-hydroxyestrone (50% and 56% increases, respectively), but reduced levels of 2-hydroxyestradiol, 2-methoxyestradiol, and 17-epiestriol (92%, 63%, and 66%, respectively), compared with animals fed a Soy− diet. Isoflavones did not have widespread effects on uterine or mammary proliferation biomarkers, whereas prior OC significantly reduced two of three proliferation end points in the endometrium. Premenopausal OCs may have long-term systemic effects on response to estrogen and its metabolism whereas postmenopausal dietary isoflavones may alter endogenous estrogen metabolism in a modest but selective manner. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2594–602)
Improved Screening for Anal Neoplasia by Immunocytochemical Detection of Minichromosome Maintenance Proteins
Authors: Scarpini Cinzia , White Victoria , Muralidhar Balaji , Patterson Aileen , Hickey Nicola , Singh Naveena , Mullerat Jose , Winslet Marc , Davies R. Justin , Phillips Marie-Louise , Stacey Pamela , Laskey Ronald A. , Miller Richard , Nathan Mayura , Coleman Nicholas
Published: October 2008

Purpose: Early detection of anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (SCC) by screening will improve clinical outcome. Assessment of anal cytology samples using routine Papanicolaou testing suffers from shortcomings in sensitivity and/or specificity, suggesting that screening tests based on biomarkers may be of value. We tested the suitability in this context of minichromosome maintenance (MCM) proteins, accurate markers of the deregulated cell cycle entry that characterizes malignancy and premalignancy.

Experimental Design: We undertook an initial immunohistochemical study of 54 anal tissue samples and validated our findings using an independent prospective cohort study of 235 anal cytology samples from 144 subjects.

Results: In the progression from normal anal epithelium through AIN to SCC, there was increasing expression of MCM2 and MCM5, including in the superficial epithelial third, the source of the majority of cells collected by anal swab. The median labeling indices (LI) for MCM2 and MCM5 in the superficial third of AIN2/3 and SCCs combined were 90.2% and 84.0%, respectively. MCM LIs in the superficial layers were significantly greater than LIs for Ki67, an alternative marker of cell cycle entry (P < 0.0001). By immunocytochemistry using a mixture of anti-MCM2 and anti-MCM5 antibodies, immunopositive cells were readily identified in anal cytology samples, even at low magnification. MCM testing showed sensitivity for AIN2/3 of 84% (95% confidence interval, 75,93) and for AIN1/viral changes of 76% (68, 84), with overall specificity (for any lesion) of 77% (64, 90).

Conclusions: MCMs are promising biomarkers for improving detection of AIN and SCC in anal cytology samples. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2855–64)
Socioeconomic Status, Negative Affect, and Modifiable Cancer Risk Factors in African-American Smokers
Authors: Kendzor Darla E. , Cofta-Woerpel Ludmila M. , Mazas Carlos A. , Li Yisheng , Vidrine Jennifer Irvin , Reitzel Lorraine R. , Costello Tracy J. , Businelle Michael S. , Ahluwalia Jasjit S. , Cinciripini Paul M. , Wetter David W.
Published: October 2008

The purpose of the present study was to describe the prevalence, patterns, and predictors of cooccurring modifiable cancer risk factors among African-Americans seeking smoking cessation treatment and to evaluate previously hypothesized models of the relationship between socioeconomic status (SES) and health behavior. Overweight/obesity, at-risk alcohol consumption, and insufficient physical activity were measured in 399 African-American smokers. Analyses indicated that 92.8% of participants had at least one cancer risk factor in addition to smoking. Univariate ordinal logistic regression analyses revealed that female gender, unemployment, lower positive affect, and greater negative affect were associated with having a greater number of cancer risk factors. Multivariate analyses yielded similar findings. A structural equation modeling approach indicated that stress/negative affect may function as one pathway linking SES and modifiable cancer risk factors among African-American smokers and that gender has a direct effect on modifiable cancer risk factors. Thus, risk patterns identified within each gender group may guide the development of multiple risk factor interventions for African-American smokers. Stress and negative affect may be an important treatment target within behavioral interventions for African-American smokers of low SES. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2546–54)
Comparing the Reliability of Responses to Telephone-Administered versus Self-Administered Web-Based Surveys in a Case-Control Study of Adult Malignant Brain Cancer
Authors: Rankin Kristin M. , Rauscher Garth H. , McCarthy Bridget , Erdal Serap , Lada Pat , Il'yasova Dora , Davis Faith
Published: October 2008

Introduction: To determine whether a Web-based survey was an acceptable method of data collection for a clinic-based case-control study of adult brain cancer, the authors compared the reliability of paired responses to a main and resurvey for participants completing surveys by telephone (n = 74) or self-administered on the Web (n = 465) between 2003 and 2006.

Methods: Recruitment of cases was done at the Evanston Northwestern Healthcare Kellogg Cancer Care Center and the Duke University Medical Center Cancer Control division, and controls were friends and siblings of cases. Twenty-five variables were examined, including smoking, oral contraceptive and residential histories, water sources, meat preparation, fruit and vegetable consumption, and pesticide use. Weighted and simple κ's were estimated for categorical and binary variables, respectively.

Results: The number of concordant paired responses was summed for use in linear regression. Respondents were 97% White and 85% had postsecondary education. Kappa's for individual questions ranged from 0.31 (duration of residence in a single family house) to 0.96 (ever smoked), with a median of 0.57 (95% confidence interval, 0.47-0.64). The median number of concordant responses was 16.2 (range, 5-22). Reliability was greater for controls than cases, Web-based versus telephone responders, females, and higher-income responders. Frequency of e-mail and Internet use was not associated with reliability.

Conclusions: A self-administered, Web-based survey was a feasible and appropriate mode of interview in this study. The comparable reliability of Web compared with telephone responses suggest that Web-based self-interviews could be a cost-effective alternative to traditional modes of interview. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2639–46)
No Effect of Red Clover–Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer
Authors: Vrieling Alina , Rookus Matti A. , Kampman Ellen , Bonfrer Johannes M.G. , Bosma Astrid , Cats Annemieke , van Doorn Jaap , Korse Catharina M. , Witteman Ben J.M. , van Leeuwen Flora E. , van't Veer Laura J. , Voskuil Dorien W.
Published: October 2008

Background: Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components.

Materials and Methods: We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover–derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas.

Results: Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, −2.0%; 95% confidence interval, −8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo.

Conclusions: The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein supplementation. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2585–93)
Lack of Prospective Associations between Plasma and Urinary Phytoestrogens and Risk of Prostate or Colorectal Cancer in the European Prospective into Cancer-Norfolk Study
Authors: Ward Heather , Chapelais Gaelle , Kuhnle Gunter G.C. , Luben Robert , Khaw Kay-Tee , Bingham Sheila
Published: October 2008

Dietary phytoestrogens are suggested to reduce the risk of prostate and colorectal cancer, but the results of epidemiologic studies have not yielded consistent support for this proposed effect, possibly due to inadequate databases of phytoestrogen levels in foods. Biomarkers of phytoestrogen intakes may provide a clearer insight into the relationship between phytoestrogen exposure and the risk of prostate or colorectal cancer risks. From the European Prospective into Cancer-Norfolk cohort (ages 45-75), serum and urine samples were analyzed for seven phytoestrogens [daidzein, enterodiol, enterolactone, genistein, glycitein, O-desmethylangolensin (O-DMA), and equol] among 193 cases of prostate cancer and 828 controls, and 221 cases of colorectal cancer with 889 controls. Summary variables of total lignans (enterodiol and enterolactone) and total isoflavones (daidzein, genistein, O-DMA, equol, and glycitein) were created and analyzed in conjunction with individual phytoestrogens. Logistic regression analyses revealed that there was no significant association between prostate cancer risk and total serum isoflavones [odds ratio (OR), 1.01; 95% confidence interval (CI), 0.93-1.10] or total serum lignans (OR, 0.94; 95% CI, 0.86-1.04) or between colorectal cancer risk and total serum isoflavones (OR, 1.01; 95% CI, 0.94-1.08) or total serum lignans (OR, 1.03; 95% CI, 0.94-1.12). Similarly, null associations were observed for individual serum phytoestrogens and for all urinary phytoestrogen biomarkers. In conclusion, we have found no evidence to support an inverse association between phytoestrogen exposure and prostate or colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2891–4)
Soy Protein Containing Isoflavones and Mammographic Density in a Randomized Controlled Trial in Postmenopausal Women
Authors: Verheus Martijn , van Gils Carla H. , Kreijkamp-Kaspers Sanne , Kok Linda , Peeters Petra H.M. , Grobbee Diederick E. , van der Schouw Yvonne T.
Published: October 2008

Background: The relatively high dietary intake of soy in Asian countries has been hypothesized to, at least partly, explain the lower breast cancer incidence patterns in these countries compared with the Western world. The aim of the present study was to determine the effect of daily soy supplementation on mammographic density, one of the strongest known risk factors for breast cancer.

Methods: A double-blind, randomized, controlled trial was conducted to compare the effects of soy protein intake containing 99 mg isoflavones daily with intake of milk protein (placebo) for the duration of 1 year. Two hundred and two Dutch postmenopausal women ages 60 to 75 years were randomized. Mammographic density was assessed using a quantitative computer-assisted method on digitized mammograms. Equol producer status was assessed in plasma provided at the final visit (soy group) or after a 3-day challenge with soy after the trial was finished (placebo group).

Results: A total of 175 women completed the baseline visits and at least one follow-up visit and were included in the intention-to-treat analyses. For 126 women, both pre- and post-trial mammograms were available. Mammographic density decreased in both study arms, but the decrease did not differ significantly between intervention and placebo groups. Equol producer status did not modify the results.

Conclusion: The results of this trial do not support the hypothesis that a diet high in soy protein among postmenopausal women decreases mammographic density. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2632–8)
Calcium, Dairy Foods, Vitamin D, and Colorectal Cancer Risk: The Fukuoka Colorectal Cancer Study
Authors: Mizoue Tetsuya , Kimura Yasumi , Toyomura Kengo , Nagano Jun , Kono Suminori , Mibu Ryuichi , Tanaka Masao , Kakeji Yoshihiro , Maehara Yoshihiko , Okamura Takeshi , Ikejiri Koji , Futami Kitaroh , Yasunami Yohichi , Maekawa Takafumi , Takenaka Kenji , Ichimiya Hitoshi , Imaizumi Nobutoshi
Published: October 2008

Epidemiologic evidence supporting a protective role of calcium and vitamin D in colorectal carcinogenesis has been accumulating in Western populations, but it is limited in Asian populations, whose intake of calcium is relatively low. We investigated the association of intakes of these nutrients with colorectal cancer risk in Japanese. Study subjects were participants of a large-scale case-control study in Fukuoka, Japan. Diet was assessed through interview regarding 148 dietary items by showing typical foods or dishes on the display of a personal computer. In a multivariate analysis adjusting for potential confounding variables, calcium intake was significantly, inversely associated with colorectal cancer risk (P for trend = 0.01); the odds ratio for the highest versus lowest quintile of calcium intake was 0.64 (95% confidence interval, 0.45-0.93). Higher levels of dietary vitamin D were significantly associated with decreased risk of colorectal cancer among those who had fewer chances of sunlight exposure at work or in leisure (P for trend = 0.02). A decreased risk of colorectal cancer associated with high calcium intake was observed among those who had higher levels of vitamin D intake or among those who had a greater chance of daily sunlight exposure, but not among those with medium or lower intake of vitamin D or among those with potentially decreased sunlight exposure. These results add to support for a joint action of calcium and vitamin D in the prevention of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2800–7)
Colorectal Adenomas in a Randomized Folate Trial: The Role of Baseline Dietary and Circulating Folate Levels
Authors: Figueiredo Jane C. , Levine A. Joan , Grau Maria V. , Barry Elizabeth L. , Ueland Per M. , Ahnen Dennis J. , Byers Tim , Bresalier Robert S. , Summers Robert W. , Bond John , McKeown-Eyssen Gail E. , Sandler Robert S. , Haile Robert W. , Baron John A.
Published: October 2008

The Aspirin/Folate Polyp Prevention Study is a randomized, placebo-controlled trial of aspirin use and folic acid supplementation and incidence of colorectal adenomas in individuals with a history of these lesions. The trial showed that folic acid supplementation does not prevent the occurrence of new adenomas and may increase risk. We extend these results by investigating whether the effect of folic acid treatment differed by baseline dietary and circulating folate levels. Diet and supplement use were ascertained at baseline through a food-frequency questionnaire; a blood sample was used to determine plasma and RBC folate levels. Individuals were followed for 3 years (first follow-up) and subsequently for an additional 3 to 5 years (second follow up). We used generalized linear regression to estimate risk ratios and 95% confidence limits as measures of association. There was little evidence that baseline dietary and total folate intake, and plasma and RBC folate modified the association between folic acid treatment and risk of any adenomas or advanced lesions. However, there was a protective association of the highest tertile of dietary and total intake as well as circulating folate with risk of any adenomas among those in the placebo group but no association among individuals in the folic acid group. Our findings support the idea that although moderate doses of folate may be protective compared with deficiency, at some point of sufficiency, supplementation provides no additional benefit. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2625–31)
Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial
Authors: Ritenbaugh Cheryl , Stanford Janet L. , Wu LieLing , Shikany James M. , Schoen Robert E. , Stefanick Marcia L. , Taylor Vicky , Garland Cedric , Frank Gail , Lane Dorothy , Mason Ellen , McNeeley S. Gene , Ascensao Joao , Chlebowski Rowan T. ,   For the Women's Health Initiative Investigators
Published: October 2008

Background: In separate Women's Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial.

Participants and Methods: 10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected.

Results: After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19).

Conclusions: In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2609–18)
Health Risk Appraisal Models for Mass Screening of Esophageal Cancer in Japanese Men
Authors: Yokoyama Tetsuji , Yokoyama Akira , Kumagai Yoshiya , Omori Tai , Kato Hoichi , Igaki Hiroyasu , Tsujinaka Toshimasa , Muto Manabu , Yokoyama Masako , Watanabe Hiroshi
Published: October 2008

Background: Because early squamous cell carcinoma (SCC) of the esophagus is detectable by endoscopic esophageal iodine staining with high accuracy and is easily treated by endoscopic mucosectomy, it is important to develop efficient methods for screening candidates for the endoscopic examination. Inactive aldehyde dehydrogenase-2 (ALDH2) is a very strong risk factor for esophageal SCC in alcohol drinkers and thus may be suitable as a screening tool.

Purpose: To assess the performance of health risk appraisal (HRA) models in screening for esophageal SCC in the Japanese male population.

Methods: Two types of HRA models were developed based on our previous case-control study, which included assessment of ALDH2 activity and selected risk factors (HRA-G and HRA-F: activities of ALDH2 assessed by genotype and questionnaire for alcohol flushing, respectively). Each individual's risk of esophageal SCC was calculated quantitatively as a risk score. The sensitivity and specificity of the HRA models at various cutoff values of risk score was estimated by a leave-one-out cross-validation. The positive predictive value was estimated assuming the prevalence of esophageal SCC in the whole population to be 0.17% or 0.39% according to literatures.

Results: When individuals ranked in the top 10% of the HRA-F risk score was screened, the sensitivity was 57.9% and positive predictive value was 0.93% or 2.12% according to the above assumptions, respectively. The sensitivity was slightly better by the HRA-G model than by the HRA-F model.

Conclusion: The HRA models may provide an important approach to early intervention strategies to control esophageal SCC in Japanese men. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2846–54)
Reproductive Factors and Risk of Meningioma and Glioma
Authors: Wigertz Annette , Lönn Stefan , Hall Per , Auvinen Anssi , Christensen Helle Collatz , Johansen Christoffer , Klæboe Lars , Salminen Tiina , Schoemaker Minouk J. , Swerdlow Anthony J. , Tynes Tore , Feychting Maria
Published: October 2008

Female sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-control study of glioma (n = 626) and meningioma (n = 906) cases and randomly selected controls stratified on age and geographic region (n = 1,774) in Denmark, Finland, Norway, Sweden, and the United Kingdom. Unconditional logistic regression was used to estimate odds ratios (OR) for glioma and meningioma in relation to reproductive factors. A decreased glioma risk was associated with ever-pregnancy compared with never-pregnancy [OR, 0.8; 95% confidence interval (95% CI), 0.6-1.0]. Meningioma risk among women ages <50 years was increased in relation to number of pregnancies leading to a live birth (OR, 1.8; 95% CI: 1.1-2.8 for giving birth to 3 children compared with nulliparous women; Ptrend among parous women = 0.01). This relation was not found for older women. Breast-feeding among parous women increased the glioma risk (OR, 2.2; 95% CI, 1.3-3.9 for breast-feeding 36 months or more compared with breast-feeding 3 months or less). Menopausal status and age at menopause were not associated with meningioma or glioma risk. Our findings imply that reproductive hormones may influence the occurrence of meningioma and glioma. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2663–70)