bluuebunny/crossref_metadata_2025 huggingface dataset:
FIRST-PRINCIPLES CALCULATIONS OF THE CaF2(111), (110), AND (100) SURFACE ELECTRONIC AND BAND STRUCTURE
Authors: EGLITIS R. I. , SHI H. , BORSTEL G.
Published: November 2006

We present and discuss the results of calculations of the CaF 2 bulk and surface electronic structure. Our results show, that the best agreement with experiment for the optical band gap (12.1 eV) can be obtained using a hybrid Hartree–Fock and density functional theory exchange functional, in which Hartree–Fock exchange is mixed with density functional theory exchange functionals, using Becke's three-parameter method, combined with the nonlocal correlation functionals by Perdew and Wang (10.96 eV). We also present calculations of CaF 2(111), (110), and (100) surfaces. Our calculated surface energies confirm that the CaF 2(111) surface is the most stable one, in agreement with the experiment.
SURFACE MODIFICATION OF STAINLESS STEEL SHEETS BY MeV ION IMPLANTATION
Authors: WANG Q. , OZAKI K. , ISHIKAWA H. , NAKANO S. , OGISO H.
Published: November 2006

Several different species of ions, Au , Fe , Ag , Ti and Si , were implanted into austenite stainless steel sheets at an energy of 3 MeV respectively. The martensite transformation induced with the ion implantation was investigated with transmission electron microscopy equipped with an energy dispersive X-ray spectrometer. The residual stresses induced with ion implantation were evaluated by the curvature technique. The effects of irradiation doses and ion species on the residual stress near surface induced by ion implantation were investigated. It is found that compressive residual stresses were induced by all the ions, and Fe and Au ions, among these ions, produced a higher level of residual stress at the same implantation. It shows that ion implantation can be employed to control and modify the internal stress near surface by changing the irradiation dose and selecting ion specie of the ion implantation.
POLYMER MICROSPHERES WITH PERMANENT ANTIBACTERIAL SURFACE FROM SURFACE-INITIATED ATOM TRANSFER RADICAL POLYMERIZATION OF 4-VINYLPYRIDINE AND QUATERNIZATION
Authors: CHENG ZHENPING , ZHU XIULIN , SHI Z. L. , NEOH K. G. , KANG E. T.
Published: November 2006

Crosslinked poly(4-vinylbenzyl chloride) (PVBC) microspheres of about 550 μm in diameter were first synthesized by suspension copolymerization of 4-vinylbenzyl chloride (VBC) in the presence of a crosslinking agent, ethylene glycol dimethacrylate (EGDMA). Subsequent surface-initiated atom transfer radical polymerization (ATRP) of 4-vinylpyridine (4VP), using the VBC units of PVBC on the microsphere surface as the macroinitiators, produced well-defined (nearly monodisperse) and covalently tethered poly(4-vinylpyridine) (P4VP) brushes. Quaternization of the tertiary amine groups of the P4VP brushes with hexyl bromide gave rise to a high concentration of quaternary ammonium salt (QAS) on the microsphere surfaces. The chemical composition of the microsphere surfaces at various stages of surface modification was characterized by X-ray photoelectron spectroscopy (XPS). The bactericidal effect of the QAS-functionalized microspheres on Escherichia coli (E. coli) was demonstrated. No significant loss in the surface bactericidal activity of the microsphere was observed during repeated applications.
THE APPLICATION OF GOLD SURFACES AND PARTICLES IN NANOTECHNOLOGY
Authors: FORD M. J. , MASENS C. , CORTIE M. B.
Published: November 2006

Gold is widely used in nanotechnology, for example as a substrate in forming self-assembled monolayers or as nanoparticles for their unique optical and chemical properties. In this paper we give an overview of the properties of gold relevant to its potential application in molecular-scale devices and present some of our recent computational predictions. Density functional calculations of molecular adsorption onto gold surfaces were used to investigate the effect of surface symmetry and identify new linking schemes for self-assembled monolayers. Adsorption energies of methylthiolate (SCH3) onto the (111), (100) and (110) surfaces of gold are predicted to be 39.3, 48.4 and 51.1 kcal/mol respectively and demonstrate that selective functionalization of the surfaces is possible. Phosphine molecules with at least two hydrogen atoms substituted for methyl groups are predicted to form Au – P surface bonds with energies of about 13–20 kcal/mol.
BARRIER HEIGHT VARIATIONS AND INTERFACE PROPERTIES OF PtSi/Si STRUCTURES
Authors: SELLAI A. , DAWSON P.
Published: November 2006

To study some of the interfacial properties of PtSi/Si diodes, Schottky structures were fabricated on (100) crystalline silicon substrates by conventional thermal evaporation of Pt on Si followed by annealing at different temperatures (from 400°C to 700°C) to form PtSi . The PtSi/n-Si diodes, all yielded Schottky barrier (SB) heights that are remarkably temperature dependent. The temperature range (20–290 K) over which the I–V characteristics were measured in the present study is broader with a much lower limit (20 K), than what is usually reported in literature. These variations in the barrier height are adequately interpreted by introducing spatial inhomogeneity into the barrier potential with a Gaussian distribution having a mean barrier of 0.76 eV and a standard deviation of 30 meV. Multi-frequency capacitance–voltage measurements suggest that the barrier is primarily controlled by the properties of the silicide–silicon interface. The forward C–V characteristics, in particular, show small peaks at low frequencies that can be ascribed to interface states rather than to a series resistance effect.
IN SITUSTUDIES OF EPITAXIAL GROWTH BY SYNCHROTRON X-RAY DIFFRACTION
Authors: BRAUN WOLFGANG , PLOOG KLAUS H.
Published: November 2006

X-rays are ideal to study the structure of crystals due to their weak interaction with matter and in most cases allow a quantitative analysis using kinematical theory. To study the incorporation of atoms during crystal growth and to analyze the kinetics on the crystal surface high primary beam intensities available at synchrotrons are required. Our studies of the molecular beam epitaxy growth of III–V semiconductors reveal that, despite their similarity in crystal structure, the surface kinetics of GaAs (001), InAs (001) and GaSb (001) differ strongly. GaAs shows an unexpectedly large coarsening exponent outside the predicted range of Ostwald ripening models during recovery. GaSb exhibits dramatically different surface morphology variations during growth and recovery. Overgrowth of GaAs by epitaxial MnAs demonstrates the ability of X-ray diffraction to follow an interface as it is buried during heteroepitaxy, which is not possible by reflection high-energy electron diffraction.
ON A NOTION OF MAPS BETWEEN ORBIFOLDS II: HOMOTOPY AND CW-COMPLEX
Authors: CHEN WEIMIN
Published: November 2006

This is the second of a series of papers which is devoted to a comprehensive theory of maps between orbifolds. In this paper, we develop a basic machinery for studying homotopy classes of such maps. It contains two parts: (1) the construction of a set of algebraic invariants — the homotopy groups, and (2) an analog of CW-complex theory. As a corollary of this machinery, the classical Whitehead theorem (which asserts that a weak homotopy equivalence is a homotopy equivalence) is extended to the orbifold category.
SYMMETRY BREAKING RESULTS FOR PROBLEMS WITH EXPONENTIAL GROWTH IN THE UNIT DISK
Authors: SECCHI SIMONE , SERRA ENRICO
Published: November 2006

We investigate some asymptotic properties of extrema uαto the two-dimensional variational problem [Formula: see text] as α → +∞. Here B is the unit disk of ℝ2and 0 < γ ≤ 4π is a given parameter. We prove that in a certain range of γ′s, the maximizers are not radial for α large.
Gene Expression Patterns Distinguish Colonoscopically Isolated Human Aberrant Crypt Foci from Normal Colonic Mucosa
Authors: Glebov Oleg K. , Rodriguez Luz M. , Soballe Peter , DeNobile John , Cliatt Janet , Nakahara Kenneth , Kirsch Ilan R.
Published: November 2006

Aberrant crypt foci (ACF) are considered the earliest identifiable preneoplastic colonic lesions; thus, a greater understanding of the nature of genetic changes underlying the transformation of normal colonic mucosa (NM) into ACF may provide insight into the mechanisms of carcinogenesis. ACF were identified by indigo carmine spraying onto colonic mucosa during colonoscopy and isolated as standard pinch biopsies of the mucosal areas containing the ACF. RNAs isolated from ACF and matched NM biopsies from the ascending and descending colons of 13 patients were analyzed on arrays containing 9128 cDNAs. Thirty-four differentially expressed (P < 0.001) genes were found in a paired comparison of the ACF and NM samples, and 25 of 26 matched pairs of ACF and NM could be correctly classified in leave-one-out cross-validation. Differential expression for seven of eight genes was confirmed by real-time reverse transcription-PCR. Furthermore, ACF and NM samples, including six pairs of ACF and NM samples that had not previously been analyzed by array hybridization, can be correctly classified on the basis of the overexpression in ACF of three selected genes (REG4, SRPN-B5, and TRIM29) evaluated by real-time reverse transcription-PCR. In a separate analysis of 13 biopsy pairs from either ascending or descending colon, ACF and NM samples could also be correctly classified by the gene expression patterns. Analysis of gene expression differences in ACF from the ascending and descending colon versus NM samples indicates that ACF from these distinct colonic locations are converging toward similar gene expression profiles and losing differences in gene expression characteristic of NM from the ascending versus descending colon. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2253–62)
Gonorrhea, Syphilis, Clinical Prostatitis, and the Risk of Prostate Cancer
Authors: Sutcliffe Siobhan , Giovannucci Edward , De Marzo Angelo M. , Leitzmann Michael F. , Willett Walter C. , Platz Elizabeth A.
Published: November 2006

Background: Although previous case-control studies have observed positive associations among gonorrhea, syphilis, clinical prostatitis, and prostate cancer, many may have been susceptible to recall and interviewer biases due to their retrospective designs. Therefore, to investigate these associations without concerns of recall and interviewer biases, we conducted a large, prospective investigation in the Health Professionals Follow-up Study.

Methods: In 1992, participants were asked to report their histories of gonorrhea, syphilis, and clinical prostatitis by mailed questionnaire. Prostate cancer diagnoses were ascertained by self-report on the 1994 and each subsequent biennial follow-up questionnaire and confirmed by medical record review.

Results: Of the 36,033 participants in this analysis, 2,263 were diagnosed with prostate cancer between the date of return of the 1992 questionnaire and 2002. No association was observed between gonorrhea [adjusted relative risk (RR), 1.04; 95% confidence interval (95% CI), 0.79-1.36] or syphilis (RR, 1.06; 95% CI, 0.44-2.59) and prostate cancer. Overall null results were also observed between clinical prostatitis and prostate cancer (RR, 1.08; 95% CI, 0.96-1.20), although a significant positive association was observed among younger men (<59 years) screened for prostate cancer (RR, 1.49; 95% CI, 1.08-2.06; Pinteraction = 0.006).

Conclusions: Gonorrhea and syphilis do not seem to be risk factors for prostate cancer in this cohort of men with a lower burden of sexually transmitted infections. Clinical prostatitis is also unlikely to be a risk factor, although possible roles for prostatitis in younger men and asymptomatic prostatic infection and inflammation cannot be ruled out. (Cancer Epidemiol Biomarkers Prev 2006;5(11):2160–6)
Cervical Cancer Screening among Women in Metropolitan Areas of the United States by Individual-Level and Area-Based Measures of Socioeconomic Status, 2000 to 2002
Authors: Coughlin Steven S. , King Jessica , Richards Thomas B. , Ekwueme Donatus U.
Published: November 2006

Background: Few studies have examined cancer screening among women residing in metropolitan areas in relation to both individual-level and area-based measures of socioeconomic status (SES). To learn more, we examined self-reported rates of Papanicolaou (Pap) testing among women living in metropolitan areas in relation to individual-level measures of SES (household income and education), and area-based measures of SES (percentage of residents living in poverty, percentage with low education, and percentage working class).

Methods: Data were obtained from women who were interviewed by telephone during 2000 and 2002 as part of the Behavioral Risk Factor Surveillance System (BRFSS). Self-reported county of residence was used to classify respondents as residents of metropolitan statistical areas. Only BRFSS respondents who resided in 35 metropolitan statistical areas with a population of ≥1.5 million in 2000 were included in this analysis. Analyses were limited to women ages ≥18 years with no history of hysterectomy (n = 49,231). Area-based measures of SES were obtained by using county-level information from the 2000 U.S. Census.

Results: Only 75.4% [95% confidence interval (95% CI), 73.8-77.1%] of 3,947 women ages ≥18 years who had a reported household income of <$15,000 per year had received a Pap test in the previous 3 years, compared with 92.2% (95% CI, 91.2-93.1%) of 18,698 women with a household income of ≥$50,000. Overall, 77.5% (95% CI, 75.7-79.3%) of women without a high school education had received a Pap test compared with 91.7% (91.0-92.3%) of college graduates. In multivariate analysis, we also found education level to be positively associated with Pap testing rates, especially among women residing in areas where a relatively low percentage of residents had a low education level (P < 0.0001).

Conclusions: Individual-level measures of SES may be modified by county-level measures of SES. Analyses of cancer screening rates by measures of income, educational attainment, and other factors may help health officials to better direct their finite resources to areas of greatest need. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2154–9)
The Methionine Synthase Polymorphism c.2756A>G Alters Susceptibility to Glioblastoma Multiforme
Authors: Semmler Alexander , Simon Matthias , Moskau Susanna , Linnebank Michael
Published: November 2006

Genetic polymorphisms of methionine metabolism, in particular methionine synthase (MTR) c.2756A>G (D919G) and methylenetetrahydrofolate reductase (MTHFR) c.677C>T (A222V), have been associated with various human cancers. We investigated MTR c.2756A>G, MTHFR c.677C>T, and a third polymorphism, transcobalamin 2 c.776C>G (P259R), for a potential association with the formation of glioblastoma multiforme. The MTR c.2756G allele was significantly underrepresented among 328 glioblastoma multiforme patients of Caucasian origin when compared with 400 population controls [patients AA/AG/GG: 0.72/0.26/0.02 and controls AA/AG/GG: 0.57/0.38/0.05, degrees of freedom = 2; χ2 = 17.86 (Pearson); P < 0.001]. No association between glioblastoma multiforme and the two other polymorphisms was observed. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2314–6)
Polymorphisms of Vitamin D Receptor and Survival in Early-Stage Non–Small Cell Lung Cancer Patients
Authors: Zhou Wei , Heist Rebecca S. , Liu Geoffrey , Neuberg Donna S. , Asomaning Kofi , Su Li , Wain John C. , Lynch Thomas J. , Giovannucci Edward , Christiani David C.
Published: November 2006

Our previous analysis suggested that surgery season in the summer time and high vitamin D intake are associated with improved survival in early-stage non–small cell lung cancer (NSCLC) patients. Here, we investigated the associations of vitamin D receptor (VDR) polymorphisms of Cdx-2 G>A, FokI C>T, and BsmI C>T with overall survival (OS) and recurrence-free survival (RFS) in 373 early-stage NSCLC patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median follow-up time was 71 months (range, 0.1-140 months), with 186 deaths and 127 recurrences. There was no association between VDR polymorphisms and survival, overall or among adenocarcinoma patients. Among squamous cell carcinoma (SCC) patients, the G/A+A/A genotype group of the Cdx-2 polymorphism was associated with better OS: the 5-year OS rates were 41% [95% confidence interval (95% CI), 28-53] for the G/G and 55% (95% CI, 39-71) for the G/A+A/A genotypes, respectively (P = 0.04, log-rank test), with the adjusted hazard ratio of 0.56 (95% CI, 0.33-0.95) for G/A+A/A versus G/G. For the joint effects of the three polymorphisms, subjects with two or more “protective” alleles have better OS among SCC patients, with the adjusted hazard ratios of 0.20 (95% CI, 0.09-0.48), 0.40 (95% CI, 0.19-0.87), and 0.43 (95% CI, 0.19-0.97), respectively, for subjects with two, three, and four or more “protective” alleles when compared with subjects with zero or one “protective” allele (Ptrend = 0.71). Similar associations were found in haplotype analysis and for RFS among SCC patients. In conclusion, VDR polymorphisms may be associated with improved survival among SCC patients of early-stage NSCLC. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2239–45)
Genetic Polymorphisms in Xenobiotic Clearance Genes and Their Influence on Disease Expression in Hereditary Nonpolyposis Colorectal Cancer Patients
Authors: Talseth Bente A. , Meldrum Cliff , Suchy Janina , Kurzawski Grzegroz , Lubinski Jan , Scott Rodney J.
Published: November 2006

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germ-line mutations in DNA mismatch repair genes. There is considerable variation in disease expression that cannot be explained by genotype/phenotype correlation, which is likely to be the result of polymorphic modifier genes. One candidate group of modifiers is the xenobiotic clearance enzyme genes that encode CYP1A1, GSTM1, GSTT1, GSTP1, and NAT2. Alterations in these xenobiotic clearance genes can potentially influence the host response to carcinogen exposure and thereby alter cancer risk. We have investigated eight polymorphisms in xenobiotic clearance genes to assess the effect on the risk of disease in mutation positive HNPCC patients.

Methods: DNA samples from 220 mutation-positive HNPCC participants (86 Australian and 134 Polish) were genotyped for single nucleotide polymorphisms (SNP) in CYP1A1, GSTM1, GSTT1, GSTP1, and NAT2. The association between the SNPs and disease characteristics, disease expression and age of diagnosis of colorectal cancer (CRC), was tested with Pearson's χ2 and Kaplan-Meier survival analysis.

Results: The HNPCC population displays a significant difference in the genotype frequency distribution between CRC patients and unaffected mismatch repair gene mutation carriers for the CYP1A1 SNP where the CRC patients harbor more of the mutant genotype.

Conclusions: Evidence from this study is not conclusive, but our data suggest that the CYP1A1 influences disease expression in individuals with HNPCC. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2307–10)
Modeling Human Metabolism of Benzene Following Occupational and Environmental Exposures
Authors: Kim Sungkyoon , Vermeulen Roel , Waidyanatha Suramya , Johnson Brent A. , Lan Qing , Smith Martyn T. , Zhang Luoping , Li Guilan , Shen Min , Yin Songnian , Rothman Nathaniel , Rappaport Stephen M.
Published: November 2006

We used natural spline (NS) models to investigate nonlinear relationships between levels of benzene metabolites (E,E-muconic acid, S-phenylmercapturic acid, phenol, hydroquinone, and catechol) and benzene exposure among 386 exposed and control workers in Tianjin, China. After adjusting for background levels (estimated from the 60 control subjects with the lowest benzene exposures), expected mean trends of all metabolite levels increased with benzene air concentrations from 0.03 to 88.9 ppm. Molar fractions for phenol, hydroquinone, and E,E-muconic acid changed continuously with increasing air concentrations, suggesting that competing CYP-mediated metabolic pathways favored E,E-muconic acid and hydroquinone below 20 ppm and favored phenol above 20 ppm. Mean trends of dose-specific levels (μmol/L/ppm benzene) of E,E-muconic acid, phenol, hydroquinone, and catechol all decreased with increasing benzene exposure, with an overall 9-fold reduction of total metabolites. Surprisingly, about 90% of the reductions in dose-specific levels occurred below about 3 ppm for each major metabolite. Using generalized linear models with NS–smoothing functions (GLM + NS models), we detected significant effects upon metabolite levels of gender, age, and smoking status. Metabolite levels were about 20% higher in females and decreased between 1% and 2% per year of life. In addition, levels of hydroquinone and catechol were greater in smoking subjects. Overall, our results indicate that benzene metabolism is highly nonlinear with increasing benzene exposure above 0.03 ppm, and that current human toxicokinetic models do not accurately predict benzene metabolism below 3 ppm. Our results also suggest that GLM + NS models are ideal for evaluating nonlinear relationships between environmental exposures and levels of human biomarkers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2246–52)
Correlates of Repeat and Recent Mammography for Women Ages 45 to 75 in the 2002 to 2003 Health Information National Trends Survey (HINTS 2003)
Authors: Rakowski William , Meissner Helen , Vernon Sally W. , Breen Nancy , Rimer Barbara , Clark Melissa A.
Published: November 2006

Background: Most national-level mammography data are for ever-had and most-recent screening. There are few national-level data on rates of repeat, on-schedule mammography, and on the prevalence and correlates of repeat mammography. It is also important to investigate the similarity of correlates for repeat and recent mammography.

Methods: Analyses were from data for women ages 45 to 75 in the 2002 to 2003 Health Information and National Trends Survey (HINTS 2003; N = 1,581). The two dependent variables were self-report of repeat mammography (two exams on schedule, based on an every-other-year interval) and recent mammography only (one mammogram within the past 2 years).

Results: The prevalence of recent mammography was 81.6% (95% confidence interval, 79.1-84.1) and for repeat mammography was 72.2% (95% confidence interval, 69.0-75.4). An access to care variable combining insurance coverage and regular source of care was the strongest sociodemographic correlate of both mammography indicators. Most other sociodemographic variables were not associated with mammography status. Five psychosocial/behavioral variables were associated with both mammography indicators (smoking status, attention to health information, knowledge of screening interval, worry about breast cancer, and recent mood status). Correlates were very similar for repeat and recent mammography.

Conclusions: Although access to care had the strongest association with mammography, psychosocial and behavioral variables did better as a group than the sociodemographic variables. A standard set of such variables should be considered for all national surveys. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2093–101)
Ethnic Disparity in the Relationship between Obesity and Plasma Insulin-Like Growth Factors: The Multiethnic Cohort
Authors: Henderson Katherine DeLellis , Goran Michael I. , Kolonel Laurence N. , Henderson Brian E. , Le Marchand Loïc
Published: November 2006

Previous studies on the relationship between obesity and circulating insulin-like growth factor (IGF) hormones show inconsistent findings and have not considered the possibility of racial/ethnic–specific differences that may exist. We therefore examined the relationship between obesity status [as measured by body mass index (BMI)] and plasma levels of the IGF proteins, IGF-I, IGF-binding protein 3 (IGFBP-3), and the molar ratio of IGF-I/IGFBP-3 in Whites, African Americans, Latinos, Japanese Americans, and Native Hawaiians from the ongoing Hawaii and Los Angeles Multiethnic Cohort Study. We measured plasma IGF-I and IGFBP-3 by ELISA in a random sample of 811 Multiethnic Cohort participants (53% male, age range = 47-82 at blood draw). In a multivariate regression of IGF-I levels, we found a statistically significant interaction between race/ethnicity and obesity status (P = 0.005). Plasma IGF-I levels declined with increasing BMI most dramatically in Latinos and Japanese. This decline was attenuated in Whites and absent in African-American and Native Hawaiian subjects. In Japanese, the quadratic term (BMI2) was statistically significant in a multivariate model (P = 0.002). In Latinos, the adjusted least-squares mean IGF-I levels in ng/mL for BMI < 25, 25 to 29.99, and ≥30 were 184.6, 147.7, and 132.7, respectively. No interaction between race/ethnicity and BMI explained the plasma IGFBP-3 levels in these data. These results may help to resolve the uncertainty in the relationship between circulating IGF levels and obesity and highlight the potential importance of racial/ethnic–specific effects among these factors in explaining ethnic disparities in obesity-related cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2298–302)
Somatic BRAF-V600E Mutations in Familial Colorectal Cancer
Authors: Vandrovcova Jana , Lagerstedt-Robinsson Kristina , Påhlman Lars , Lindblom Annika
Published: November 2006

The BRAF gene is mutated in 4% to 12% of unselected colorectal cancers, particularly those with high microsatellite instability and in premalignant lesions, such as serrated adenomas and hyperplastic polyps. However, it has been shown that activating BRAF mutations are almost never found in tumors from hereditary nonpolyposis colorectal cancer patients. To evaluate the role of oncogenic BRAF mutations in non-hereditary nonpolyposis colorectal cancer/non-familial adenomatous polyposis familial colorectal cancer, we did a mutation screening of the most common BRAF mutation, the V600E mutation, in 194 colorectal tumors from patients with a positive family history of the disease. The BRAF-V600E mutation was identified in 100% (8 of 8) of microsatellite-unstable tumors and in 9.7% (18 of 186) of microsatellite-stable tumors. Interestingly, families with extracolonic tumors showed a much higher mutation frequency (17.5%) compared with families with colonic cancer only (3.5%; P = 0.009). In addition, we studied colonoscopic results from 448 family members who had been under colonoscopic surveillance for several years. Subjects from families where the V600E mutation was identified had less adenomas compared with those from families where no BRAF mutation had been found (odds ratio, 8.5; 95% confidence interval, 1.1-64.6). These findings indicate that adenomas might be less important in the cancer development in the group of families with BRAF-V600E mutations and indirectly support a previous hypothesis that tumors might develop through the hyperplastic polyp-serrated adenoma pathway. In conclusion, our results suggest that BRAF-V600E mutations are mainly involved in colorectal cancer families characterized by an increased risk of other common malignancies. (Cancer Epidemiol Biomarkers Prev 2006;66(23):2270–3)
Adolescent Milk Fat and Galactose Consumption and Testicular Germ Cell Cancer
Authors: Stang Andreas , Ahrens Wolfgang , Baumgardt-Elms Cornelia , Stegmaier Christa , Merzenich Hiltrud , de Vrese Michael , Schrezenmeir Jürgen , Jöckel Karl-Heinz
Published: November 2006

Recent case-control studies suggested that dairy product consumption is an important risk factor for testicular cancer. We examined the association between consumption of dairy products, especially milk, milk fat, and galactose, and testicular cancer in a population-based case-control study including 269 case and 797 controls (response proportions of 76% and 46%, respectively). Dietary history was assessed by food frequency questions for the index persons and through their mothers including diet 1 year before interview and diet at age 17 years. We used conditional logistic regression to calculate odds ratios as estimates of the relative risk (RR), 95% confidence intervals (95% CI), and to control for social status and height. The RR of testicular cancer was 1.37 (95% CI, 1.12-1.68) per additional 20 servings of milk per month (each 200 mL) in adolescence. This elevated overall risk was mainly due to an increased risk for seminoma (RR, 1.66; 95% CI, 1.30-2.12) per additional 20 milk servings per month. The RR for seminoma was 1.30 (95% CI, 1.15-1.48) for each additional 200 g milk fat per month and was 2.01 (95% CI, 1.41-2.86) for each additional 200 g galactose per month during adolescence. Our results suggest that milk fat and/or galactose may explain the association between milk and dairy product consumption and seminomatous testicular cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2189–95)
Antibiotics and Risk of Breast Cancer: Up to 9 Years of Follow-up of 2.1 Million Women
Authors: Friedman Gary D. , Oestreicher Nina , Chan James , Quesenberry Charles P. , Udaltsova Natalia , Habel Laurel A.
Published: November 2006

Antibiotic use has been associated with risk of breast cancer in previous reports. Using Cox proportional hazards analysis, we evaluated this association in 2,130,829 adult female subscribers of a health care program according to their receipt of prescriptions of antibiotics from outpatient pharmacies. Hormone use was taken into account. Altogether, 18,521 women developed breast cancer in up to 9.4 years of follow-up. Use of any antibiotic was associated with slightly increased risk [hazard ratio (HR), 1.14; 95% confidence interval (95% CI), 1.10-1.18] but there was little, if any, evidence of dose response, with HR of 1.17 (95% CI, 0.97-1.42) for >1,000 days of use compared with no use. The only two weakly associated antibiotic groups (HR >1.10 for >100 days of use) were tetracyclines and macrolides with HRs (95% CI) of 1.23 (1.11-1.36) and 1.16 (0.98-1.36), respectively. An association of lincosamides with breast cancer in an earlier, smaller database was not confirmed, but follow-up was too short in the present data for adequate evaluation. Medical record review suggested that acne and/or rosacea could be the underlying factor, associated with long-term antibiotic therapy and found by others to be associated with risk of breast cancer. Although causality cannot be ruled out, the observed associations of antibiotics overall, tetracyclines, and macrolides with breast cancer were weak and could be explained by uncontrolled confounding by the diseases being treated or by other factors. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2102–6)
Risk Group, Skin Lesion History, and Sun Sensitivity Reliability in Squamous Cell Skin Cancer Progression
Authors: Clouser Mary C. , Harris Robin B. , Roe Denise J. , Saboda Kathylynn , Ranger-Moore James , Duckett Laura , Alberts David S.
Published: November 2006

In studies of skin cancer, participants are often classified into risk groups based on self-reported history of sun exposure or skin characteristics. We sought to determine the reliability of self-reported skin characteristics among participants of a study to evaluate markers for nonmelanoma skin cancer (NMSC). Multiple questionnaires and screening protocols were administered over a 3-month period to individuals from three risk groups: existing sun damage on forearms but no visible actinic keratoses (n = 91), visible actinic keratoses (n = 38), and history of resected squamous cell skin cancer in the last 12 months (n = 35). We assessed consistency of risk group assignment between telephone screen and study dermatologist assignment, self-reported sun sensitivity (telephone recruitment form versus participant completed profile), and self-reported history of NMSC skin lesions (telephone recruitment form versus health history). There was substantial agreement between probable risk group and final assignment (κ = 0.76; 95% confidence interval, 0.65-0.85) and agreement did not differ by gender. Agreement for self-reported sun sensitivity was moderate (κ weighted = 0.46; 95% confidence interval, 0.36-0.56) with higher agreement for women. For self-reported NMSC lesion history between two interviews, 24 days apart, κ estimates ranged from 0.66 to 0.78 and were higher for women than men. Overall, there was evidence for substantial reproducibility related to risk group assignment and self-reported history of NMSC, with self-reported sun sensitivity being less reliable. In all comparisons, women had higher κ values than men. These results suggest that self-reported measures of skin cancer risk are reasonably reliable for use in screening subjects into studies. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2292–7)
A Meta-analysis of Diabetes Mellitus and the Risk of Prostate Cancer
Authors: Kasper Jocelyn S. , Giovannucci Edward
Published: November 2006

Background: Studies investigating the association between diabetes mellitus and prostate cancer have reported inconsistent findings. We examined this association by conducting a detailed meta-analysis of the studies published on the subject.

Methods: MEDLINE and EMBASE databases and bibliographies of retrieved articles were searched. Studies investigating the relationship between diabetes mellitus and prostate cancer were included in the meta-analysis. Potential sources of heterogeneity between studies were explored and publication bias was evaluated. Pooled relative risk (RR) was calculated using the random-effects model. Numerous relevant subgroup analyses were also done.

Results: We included 19 studies, published between 1971 and 2005, in the meta-analysis and found an inverse association between diabetes mellitus and prostate cancer [RR, 0.84, 95% confidence interval (CI), 0.76-0.93, P for heterogeneity ≤ 0.01]. For cohort studies alone, the RR was 0.81 (95% CI, 0.71-0.92, P for heterogeneity ≤ 0.01) and for case-control studies alone, the RR was 0.89 (95% CI, 0.72-1.11, P for heterogeneity = 0.02). The significant heterogeneity was mitigated in some of the subgroup analyses. For studies conducted before prostate-specific antigen screening was introduced as a common procedure, the RR was 0.94 (95% CI, 0.85-1.03, P for heterogeneity = 0.15), and for studies conducted after this time, the RR was 0.73 (95% CI, 0.64-0.83, P for heterogeneity = 0.10). For studies that adjusted for three or more potential confounders, the RR was 0.74 (95% CI, 0.65-0.85, P for heterogeneity = 0.06) and for studies that adjusted for less than three potential confounders, the RR was 0.93 (95% CI, 0.86-1.02, P for heterogeneity = 0.18).

Conclusion: This study suggests an inverse relationship between diabetes and prostate cancer. Potential biological mechanisms underlying this association, as well as possible biases, are discussed. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2056–62)
The Epidemiology of Second Primary Cancers
Authors: Travis Lois B.
Published: November 2006

Background: Due to improvements in early detection, supportive care, and treatment, the number of cancer survivors in the United States has tripled since 1971 and is growing by 2% each year. In 2001, there were ∼10 million cancer survivors, representing 3.5% of the population. As survival after a diagnosis of cancer improves, quantification of the late effects of cancer and its therapy become critical. One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. Second- or higher-order cancers now account for ∼16% of incident cancers reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Subsequent neoplasms may not necessarily be attributable to prior cancer treatment but may also reflect the effect of shared etiologic factors, environmental exposures, host characteristics, and combinations of influences, including gene-environment and gene-gene interactions.

Methods/Results: This review will focus on selected highlights and recent findings in treatment-associated malignancies, with an emphasis on survivors of adult cancer. Current study methods will also be summarized.

Conclusions: Important opportunities for future research include the prospective identification of patient subgroups that might be at heightened susceptibility of developing therapy-associated second cancers to modify planned treatments or select alternative management strategies. For the burgeoning population of cancer survivors treated successfully with past regimens, including those therapies that have been subsequently refined, continued quantification of late effects, including second cancers, remains highly relevant in terms of raising clinician and patient awareness, for informed counseling, and for the development of risk-adapted long-term management strategies. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2020–6)
Chemoprevention of Second Cancers
Authors: Mayne Susan T. , Cartmel Brenda
Published: November 2006

Background: “Second cancers” can be thought of in two general categories: (a) those occurring as a consequence of cancer treatment and (b) primary cancers that are thought to develop largely as a consequence of prior lifestyle habits (e.g., chronic smoking, drinking, sun exposures), genetic susceptibility, or interactions of the two. Because there has been limited work on chemoprevention of treatment-related secondary cancers, this minireview will focus on chemoprevention of second cancers with lifestyle/genetic origins.

Methods/Results: Trials aimed at preventing second cancers in patients with tobacco-related cancers (head and neck, lung), skin cancers, breast cancer, and colorectal adenomatous polyps have been completed with some success. However, one finding that has emerged is that, across several cancer sites, subgroups are found with differential response to the chemopreventive agent. For example, smoking status, alcohol consumption, nutritional status, and host tumor characteristics seem to modify chemopreventive efficacy. Stratum-specific (subgroup) findings may occur by chance, requiring a need for supportive evidence from observational epidemiologic studies of the agent (where available), mechanistic studies, or results of other related trials.

Conclusions: Although chemoprevention of second cancers has been realized, it has become increasingly apparent that not all benefit equally. The finding of subgroup effects in completed trials results in the need to consider such subgroup effects in the design of future trials, by either restricting enrollment to particular subgroups (e.g., never or former smokers), or by increasing sample size requirements to allow for variation in response in subgroups in a statistically powerful way. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2033–7)
Higher Methylation Levels in Gastric Mucosae Significantly Correlate with Higher Risk of Gastric Cancers
Authors: Nakajima Takeshi , Maekita Takao , Oda Ichiro , Gotoda Takuji , Yamamoto Seiichiro , Umemura Satoshi , Ichinose Masao , Sugimura Takashi , Ushijima Toshikazu , Saito Daizo
Published: November 2006

Background: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori–negative cases with a gastric cancer had higher methylation levels than those of H. pylori–negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers.

Methods: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands.

Results: In H. pylori–negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori–positive individuals were increased to various degrees in all the three groups.

Conclusions: In H. pylori–negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2317–21)
Interleukin-6-Related Genotypes, Body Mass Index, and Risk of Multiple Myeloma and Plasmacytoma
Authors: Cozen Wendy , Gebregziabher Mulugeta , Conti David V. , Van Den Berg David J. , Coetzee Gerhard A. , Wang Sophia S. , Rothman Nathaniel , Bernstein Leslie , Hartge Patricia , Morhbacher Ann , Coetzee Simon G. , Salam Muhammad T. , Wang Wei , Zadnick John , Ingles Sue A.
Published: November 2006

Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions −174, −572, and −597; one variable number of tandem repeats (−373 AnTn); and one SNP in the IL-6 receptor (IL-6rα) gene at position −358. The variant allele of the IL-6 promoter SNP −572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The −373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI ≥ 30 kg/m2) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m2. These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2285–91)
Genetic Variation in the Nucleotide Excision Repair Pathway and Colorectal Cancer Risk
Authors: Berndt Sonja I. , Platz Elizabeth A. , Fallin M. Daniele , Thuita Lucy W. , Hoffman Sandra C. , Helzlsouer Kathy J.
Published: November 2006

Nucleotide excision repair (NER) enzymes are critical for the removal of bulky DNA adducts caused by environmental carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons, which are found in two putative risk factors for colorectal cancer, tobacco smoke and meat cooked at high temperature. To examine the association between common genetic variants in NER genes and the risk of colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Twenty-two single nucleotide polymorphisms in 11 NER genes were genotyped in 250 colorectal cancer cases and a subcohort of 2,224 participants. Incidence rate ratios (RR) and 95% confidence intervals (95% CI) were estimated using a modified Cox regression model and robust variance estimate. The ERCC6 1213G variant, which is thought to reduce NER capacity, was associated with an increased risk of colorectal cancer compared with the homozygous wild type (RR, 1.36; 95% CI, 1.00-1.86 and RR, 2.64; 95% CI, 1.53-4.58 for the RG and GG genotypes respectively with Ptrend = 0.0006). Having at least one XPC 492H allele was also associated with an increased risk of colorectal cancer (RR, 1.75; 95% CI, 1.20-2.57). When the combined effects of ERCC6 R1213G and XPC R492H were examined, the risk of colorectal cancer significantly increased with increasing number of variant alleles (Ptrend = 0.00003). Our study suggests that genetic polymorphisms in the NER genes, ERCC6 and XPC, may be associated with an increased risk of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2263–9)
Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival
Authors: Long Ji-Rong , Kataoka Nobuhiko , Shu Xiao-Ou , Wen Wanqing , Gao Yu-Tang , Cai Qiuyin , Zheng Wei
Published: November 2006

The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus may be related to the progression of breast cancer. We examined the association between CYP19A1 genetic polymorphisms and breast cancer survival in a cohort of 1,136 patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and who has donated a DNA sample to the study. Patients were followed for cancer recurrence and mortality through July 2005. Nineteen haplotype tagging single-nucleotide polymorphisms (SNP) in the CYP19A1 gene were evaluated. For each of the five SNPs located in haplotype block 2, patients homozygous for the minor alleles had a reduced 5-year disease-free survival rate compared with those carrying the major allele. The age-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were 1.5 (1.1-2.1), 2.1 (1.2-3.6), 1.5 (1.1-2.0), 1.4 (1.0-2.0), and 1.4 (1.0-2.0) for hCV1664178, rs12900137, rs730154, rs936306, and rs1902586, respectively. Haplotype analyses showed that the haplotype CCCTA (all minor alleles of the five SNPs in block 2) was associated with decreased disease-free survival (HR, 1.9; 95% CI, 1.1-3.3). The nonsynonymous SNP, rs700519 (Arg264Cys), located in haplotype block 4, was also associated with breast cancer survival. The age-adjusted HR for the Cys/Cys (T/T) genotype was 2.2 (95% CI, 1.2-4.1) for overall survival and 2.1 (95% CI, 1.1-3.9) for disease-free survival, compared with those carrying the Arg (C) allele. These results suggest that polymorphisms in the CYP19A1 gene may have effects on breast cancer prognosis. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2115–22)
Physical Activity and Risk of Endometrial Cancer: A Population-Based Prospective Cohort Study
Authors: Friberg Emilie , Mantzoros Christos S. , Wolk Alicja
Published: November 2006

Physical activity is involved in the regulation of metabolic and hormonal pathways and is one of the factors important for the maintenance of body weight; obesity is a risk factor for endometrial cancer. A connection between physical activity and endometrial cancer risk through hormonal mechanisms, possibly mediated by body weight, is biologically plausible. Only one study has investigated total physical activity, and no previous study has examined leisure time inactivity directly. We investigated the association of total physical activity and different types of physical activity with risk of endometrial cancer in the Swedish Mammography Cohort, a population-based prospective cohort, including 33,723 women and 199 endometrial cancer cases. After adjustments for potential confounders (age, body mass index, parity, history of diabetes, total fruit and vegetable intake, and education), the relative risks for endometrial cancer for the second to fourth quartile of total physical activity compared with the lowest one were 0.80 [95% confidence interval (95% CI), 0.54-1.18], 0.87 (95% CI, 0.59-1.28), and 0.79 (95% CI, 0.53-1.17). High leisure time inactivity (watching TV/sitting ≥5 hours daily) compared with low was associated with increased risk of endometrial cancer (relative risk, 1.66; 95% CI, 1.05-2.61). The associations were not modified by body mass index. Findings from this study suggest that total physical activity is weakly inversely associated with endometrial cancer risk and that leisure time inactivity is statistically significantly associated with increased risk for endometrial cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2136–40)