bluuebunny/crossref_metadata_2025 huggingface dataset:
Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death
Authors: Sridhar Arun , Nishijima Yoshinori , Terentyev Dmitry , Terentyeva Radmila , Uelmen Rebecca , Kukielka Monica , Bonilla Ingrid M. , Robertson Gail A. , Györke Sandor , Billman George E. , Carnes Cynthia A.
Published: September 2008

Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD); a healed myocardial infarction increases the risk of SCD. We determined the contribution of specific repolarization abnormalities to ventricular tachyarrhythmias in a postinfarction model of SCD. For our methods, we used a postinfarction canine model of SCD, where an exercise and ischemia test was used to stratify animals as either susceptible (VF+) or resistant (VF−) to sustained ventricular tachyarrhythmias. Our results show no changes in global left ventricular contractility or volumes occurred after infarction. At 8–10 wk postmyocardial infarction, myocytes were isolated from the left ventricular midmyocardial wall and studied. In the VF+ animals, myocyte action potential (AP) prolongation occurred at 50 and 90% repolarization ( P < 0.05) and was associated with increased variability of AP duration and afterdepolarizations. Multiple repolarizing K+ currents ( IKr, Ito) and inward IK1 were also reduced ( P < 0.05) in myocytes from VF+ animals compared with control, noninfarcted dogs. In contrast, only Ito was reduced in VF− myocytes compared with controls ( P < 0.05). While afterdepolarizations were not elicited at baseline in myocytes from VF− animals, afterdepolarizations were consistently elicited after the addition of an IKr blocker. In conclusion, the loss of repolarization reserve via reductions in multiple repolarizing currents in the VF+ myocytes leads to AP prolongation, repolarization instability, and afterdepolarizations in myocytes from animals susceptible to SCD. These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias.
Quantifying the Neural Elements Activated and Inhibited by Globus Pallidus Deep Brain Stimulation
Authors: Johnson Matthew D. , McIntyre Cameron C.
Published: September 2008

Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective therapy option for controlling the motor symptoms of medication-refractory Parkinson's disease and dystonia. Despite the clinical successes of GPi DBS, the precise therapeutic mechanisms are unclear and questions remain on the optimal electrode placement and stimulation parameter selection strategies. In this study, we developed a three-dimensional computational model of GPi-DBS in nonhuman primates to investigate how membrane channel dynamics, synaptic inputs, and axonal collateralization contribute to the neural responses generated during stimulation. We focused our analysis on three general neural elements that surround GPi-DBS electrodes: GPi somatodendritic segments, GPi efferent axons, and globus pallidus pars externa (GPe) fibers of passage. During high-frequency electrical stimulation (136 Hz), somatic activity in the GPi showed interpulse excitatory phases at 1–3 and 4–5.5 ms. When including stimulation-induced GABAA and AMPA receptor dynamics into the model, the somatic firing patterns continued to be entrained to the stimulation, but the overall firing rate was reduced (78.7 to 25.0 Hz, P < 0.001). In contrast, axonal output from GPi neurons remained largely time-locked to each pulse of the stimulation train. Similar entrainment was also observed in GPe efferents, a majority of which have been shown to project through GPi en route to the subthalamic nucleus. The models suggest that pallidal DBS may have broader network effects than previously realized and the modes of therapy may depend on the relative proportion of GPi and/or GPe efferents that are directly affected by the stimulation.
The Initial Disparity Vergence Elicited With Single and Dual Grating Stimuli in Monkeys: Evidence for Disparity Energy Sensing and Nonlinear Interactions
Authors: Miura K. , Sugita Y. , Matsuura K. , Inaba N. , Kawano K. , Miles F. A.
Published: September 2008

We recorded the initial vertical vergence eye movements elicited in monkeys at short latency (∼70 ms) when the two eyes see one-dimensional (1D) horizontal grating patterns that are identical except for a phase difference (disparity) of one-quarter wavelength. With gratings composed of single sine waves, responses were always compensatory, showing Gaussian dependence on log spatial frequency (on average: peak = 0.75 cycles/deg; SD = 0.74; r2 = 0.980) and monotonic dependence on log contrast with a gradual saturation well described by the Naka-Rushton equation (on average: n = 0.89; C50 = 4.1%; r2 = 0.978). With gratings composed of two sine waves whose spatial frequencies were in the ratio 3:5 and whose disparities were of opposite sign (the 3f5f stimulus), responses were determined by the disparities and contrasts of the two sine-wave components rather than the disparity of the features, consistent with early spatial filtering of the monocular inputs before their binocular combination and mediation by detectors sensitive to disparity energy. In addition, responses to the 3f5f stimulus showed a nonlinear dependence on the relative contrasts of the two sine waves. Thus on average, when the contrast of one sine wave was 2.3 times greater than that of the other, the one with the lower contrast was largely ineffective as though suppressed, and responses were determined almost entirely by the sine wave of higher contrast: Winner-Take-All. These findings are very similar to those published previously on the vertical vergence responses of humans, indicating that the monkey provides a good animal model for studying these disparity vergence responses.
Updating Visual Memory Across Eye Movements for Ocular and Arm Motor Control
Authors: Thompson Aidan A. , Henriques Denise Y. P.
Published: September 2008

Remembered object locations are stored in an eye-fixed reference frame, so that every time the eyes move, spatial representations must be updated for the arm-motor system to reflect the target's new relative position. To date, studies have not investigated how the brain updates these spatial representations during other types of eye movements, such as smooth-pursuit. Further, it is unclear what information is used in spatial updating. To address these questions we investigated whether remembered locations of pointing targets are updated following smooth-pursuit eye movements, as they are following saccades, and also investigated the role of visual information in estimating eye-movement amplitude for updating spatial memory. Misestimates of eye-movement amplitude were induced when participants visually tracked stimuli presented with a background that moved in either the same or opposite direction of the eye before pointing or looking back to the remembered target location. We found that gaze-dependent pointing errors were similar following saccades and smooth-pursuit and that incongruent background motion did result in a misestimate of eye-movement amplitude. However, the background motion had no effect on spatial updating for pointing, but did when subjects made a return saccade, suggesting that the oculomotor and arm-motor systems may rely on different sources of information for spatial updating.
A Pilot Study of Compositional Analysis of the Breast and Estimation of Breast Mammographic Density Using Three-Dimensional T1-Weighted Magnetic Resonance Imaging
Authors: Khazen Michael , Warren Ruth M.L. , Boggis Caroline R.M. , Bryant Emilie C. , Reed Sadie , Warsi Iqbal , Pointon Linda J. , Kwan-Lim Gek E. , Thompson Deborah , Eeles Ros , Easton Doug , Evans D. Gareth , Leach Martin O. ,   for the Collaborators in the United Kingdom Medical Research Council Magnetic Resonance Imaging in Breast Screening (MARIBS) Study
Published: September 2008

Purpose: A method and computer tool to estimate percentage magnetic resonance (MR) imaging (MRI) breast density using three-dimensional T1-weighted MRI is introduced, and compared with mammographic percentage density [X-ray mammography (XRM)].

Materials and Methods: Ethical approval and informed consent were obtained. A method to assess MRI breast density as percentage volume occupied by water-containing tissue on three-dimensional T1-weighted MR images is described and applied in a pilot study to 138 subjects who were imaged by both MRI and XRM during the Magnetic Resonance Imaging in Breast Screening study. For comparison, percentage mammographic density was measured from matching XRMs as a ratio of dense to total projection areas scored visually using a 21-point score and measured by applying a two-dimensional interactive program (CUMULUS). The MRI and XRM percent methods were compared, including assessment of left-right and interreader consistency.

Results: Percent MRI density correlated strongly (r = 0.78; P < 0.0001) with percent mammographic density estimated using Cumulus. Comparison with visual assessment also showed a strong correlation. The mammographic methods overestimate density compared with MRI volumetric assessment by a factor approaching 2.

Discussion: MRI provides direct three-dimensional measurement of the proportion of water-based tissue in the breast. It correlates well with visual and computerized percent mammographic density measurements. This method may have direct application in women having breast cancer screening by breast MRI and may aid in determination of risk.(Cancer Epidemiol Biomarkers Prev 2008;17(9):2268–74)
Sun Exposure and the Incidence of Melanocytic Nevi in Young Australian Children
Authors: Harrison Simone Lee , MacLennan Robert , Buettner Petra Gertraud
Published: September 2008

The number of melanocytic nevi (MN) is an important risk factor for cutaneous melanoma. The present study further investigated the relationship between sun exposure, the incidence of MN, and the prevalence of large acquired MN (≥5 mm). A cohort of 479 preschool children born in Townsville, Australia was examined for MN in 1991 and a year later. Sun exposure was assessed by questionnaire. The erythemally effective dose of solar UV radiation was estimated from questionnaire data combined with local UV biometry. Almost all (97.7%) children had acquired new MN (median, 12), with a median incidence rate of 11.0 per year (interquartile range, 7.0-16.5). Total number of hours of sun exposure during follow-up (P = 0.034) and tendency to burn (P = 0.028) were independent risk factors for MN incidence. Sunburn experience during follow-up failed to reach significance when adjusted for tendency to burn. Lifetime number of sunburns (P < 0.001) and the severity of sunburns experienced during follow-up (P < 0.001) were significantly related to the presence of large acquired MN at follow-up. Reducing the total number of hours of sun exposure is particularly relevant in sun-sensitive children and may restrain the development of MN, whereas avoiding sunburn in young children might prevent large MN, subsequently reducing the risk of melanoma. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2318–24)
Common 8q24 Sequence Variations Are Associated with Asian Indian Advanced Prostate Cancer Risk
Authors: Tan Ying-Cai , Zeigler-Johnson Charnita , Mittal Rama D. , Mandhani Anil , Mital Balraj , Rebbeck Timothy R. , Rennert Hanna
Published: September 2008

Three sequence variations (rs1447295, rs16901979, and rs6983267) on 8q24 were recently shown to independently affect prostate cancer risk. Asian Indians have a low prostate cancer risk; however, in the absence of screening practices for the disease, most are diagnosed with metastatic prostate cancer. We evaluated the association of these single nucleotide polymorphisms (SNP) with advanced prostate cancer in 153 prostate cancer cases and 227 age-matched controls (northern India). Overall, there was a positive association between carriers of the allele A of rs1447295 and prostate cancer risk [odds ratio (OR), 1.60; 95% confidence interval (95% CI), 1.01-2.52] but no significant association with carriers of alleles A of rs16901979 and allele G of rs6983267. However, significant associations were observed for both SNPs in men with high Gleason scores (≥7) and metastasis. Adjusting for age, the ORs were 1.77 (95% CI, 1.05-2.97) for carriers of rs1447295 A and 1.85 (95% CI, 1.04-3.28) for carriers of the rs16901979 A allele. We also observed significant joint effects among these loci associated with prostate cancer risk and severity, suggestive of additive effects of the independent SNPs. The ORs for the combined effects of rs1447295 A with rs16901979 A or rs6983267 G were 2.61 (95% CI, 1.11-6.12) and 1.84 (95% CI, 1.12-3.06), respectively. There was no joint effect between SNPs rs16901979 A and rs6983267 G. These results confirm the significance of these SNPs in prostate cancer etiology in a previously unstudied population who do not undergo prostate cancer screening and are diagnosed with severe disease. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2431–5)
Discovery of Novel Biomarkers in Oral Submucous Fibrosis by Microarray Analysis
Authors: Li Ning , Jian Xinchun , Hu Yanjia , Xu Chunjiao , Yao Zhigang , Zhong Xiaohuan
Published: September 2008

Oral submucous fibrosis (OSF) is a high-risk precancerous condition of the oral cavity. Areca nut chewing is its key etiologic factor, but the full pathogenesis is still obscure. In this study, microarray analysis was used to characterize the mRNA changes of 14,500 genes in four OSF and four normal buccal mucosa samples to identify novel biomarkers of OSF. Five candidate genes with the most differential changes were chosen for validation. The correlation between clinicopathologic variables of 66 OSF patients and the expression of each gene was assessed by immunohistochemistry. The microarray analysis showed that 661 genes were up-regulated (fold value >2) and 129 genes were down-regulated (fold value <0.5) in OSF (q < 0.01). The top three up-regulated genes [Loricrin, Cartilage oligomeric matrix protein (COMP), Cys-X-Cys ligand 9 (CXCL9)] with the largest fold changes and the top two down-regulated genes [keratin 19 (KRT19), cytochrome P450 3A5 (CYP 3A5)] with the most significantly differential changes in OSF were chosen as candidate biomarkers. In immunohistochemical results, the expression of Loricrin and COMP showed statistically significant association with histologic grade of OSF (P = 0.03 and 0.006, respectively). COMP was found to be overexpressed frequently in patients with the habit of areca nut chewing for more than 4 years (P = 0.002). CYP 3A5 was revealed an inverse correlation with histologic grade (P = 0.04). This pilot study showed that five novel genes might play important roles in the pathogenesis of OSF and may be clinically useful for early detection of OSF. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2249–59)
Differential Expression of Parathyroid Hormone–Related Protein in Adrenocortical Tumors: Autocrine/Paracrine Effects on the Growth and Signaling Pathways in H295R Cells
Authors: Rizk-Rabin Marthe , Assie Guillaume , Rene-Corail Fernande , Perlemoine Karine , Hamzaoui Hinda , Tissier Fréderique , Lieberherr Michele , Bertagna Xavier , Bertherat Jerome , Bouizar Zhor
Published: September 2008

Adrenocortical tumors (ACT) are rare and heterogeneous, but their pathogenesis is unclear. The oncoprotein parathyroid hormone–related protein (PTHrP), found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the PTH-R1 receptor. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinomas (ACC) and 13 adrenocortical adenomas (ACA), and investigated the effects of PTHrP(1-34) on H295R cells derived from an ACC. PTH-R1 mRNA and proteins were detected by real-time PCR and Western blotting in all the ACT samples and in H295R cells. Their concentrations did not differ significantly from one ACT to another. PTHrP mRNA was assayed by quantitative real-time PCR. It was detected in 90% of ACC, and in 10% of ACA. There was a positive correlation with the prognostic factors, McFarlane stage and Weiss score. Tissue-specific PTHrP protein processing was shown by Western blotting. Immunohistochemical staining revealed numerous, dense foci of PTHrP-containing cells in ACC, but few positive cells in ACA or normal tissue. PTHrP stimulated the growth of H295R cells, whereas a specific anti-PTHrP antibody and a PTHrP-R1 antagonist both enhanced their apoptosis. PTHrP activated both adenylate cyclase/protein kinase A and the intracellular calcium/protein kinase C pathways via PTHrP-R1. The active synthesis of PTHrP is linked to poor prognosis in ACC, in which it may act as an autocrine/paracrine factor in tumor growth and malignancy. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2275–85)
Descriptive Evidence That Risk Profiles for Cervical Intraepithelial Neoplasia 1, 2, and 3 Are Unique
Authors: Belinson Suzanne , Smith Jennifer S. , Myers Evan , Olshan Andrew , Belinson Jerome , Pretorius Robert , Qiao You-lin , Hartmann Katherine
Published: September 2008

Objective: This study aimed to estimate if risk factor profiles for histologically confirmed cervical intraepithelial neoplasia (CIN) 2 lesions differ from those for CIN 1 or 3.

Methods: A total of 2,055 women positive for high-risk human papillomavirus, with a minimum of five cervical biopsies, were enrolled in the Shanxi Province Cervical Cancer Screening Study II. We evaluated risk factor profiles for CIN 2 in comparison with CIN 1 and 3. Polytomous logistic regression was used to generate odds ratios and corresponding 95% confidence intervals and to test for differences in odds ratios across histologic grades.

Results: The risk for CIN 3 associated with three or more pregnancies and sexual intercourse within 4 months of childbirth was higher than that for CIN 2 (Pdifference = 0.02 and 0.0007, respectively). Significant differences in the associations of age groups with CIN 1 and 2 were observed, such that there were positive associations with CIN 2 but none for CIN 1. There was no difference in the association of number of sexual partners or reported number of abortions between CIN 1 and 2 or between CIN 3 and 2.

Conclusions: In our study, the patterns of risk factor profiles for CIN 1, 2, and 3 were unique. Conventional grouping of CIN 2 with 3 for analysis of risk factors may need revisiting. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2350–5)
Personal Background and Cognitive Factors as Predictors of the Intention to be Screened for Stomach Cancer
Authors: Hahm Myung-Il , Choi Kui Son , Park Eun-Cheol , Kwak Min-Son , Lee Hoo-Yeon , Hwang Seung Sik
Published: September 2008

Although stomach cancer screening is effective for reducing mortality, it is underutilized in Korea. By applying an extended theory of planned behavior model, our objective was to determine how personal background factors influence a patient's inclination to be screened for stomach cancer. The study population was derived from the 2006 Korean National Cancer Screening Survey, which was done to investigate the participation of the general population in cancer screening. In total, 1,509 Koreans who were 40 to 70 years old participated in this study. Path analysis was used to test a conceptual model in which (a) factors considered as precursors to be screened (components in theory of planned behavior model) directly predicted the intention to be screened and (b) personal background factors, including sociodemographic factors, previous screening experience, economic status, and perceived risk, indirectly influenced the intention to be screened through their effects on cognitive components such as attitude and subjective norm in the theory of planned behavior model. Most of the personal background factors did not directly influence intention but instead influenced cognitive elements in the theory of planned behavior model. Attitude and perceived behavioral control were well correlated with a patient's intention, regardless of the screening cost. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2473–9)
Methylene Tetrahydrofolate Reductase Genotype Modifies the Chemopreventive Effect of Folate in Colorectal Adenoma, but not Colorectal Cancer
Authors: Lightfoot Tracy J. , Barrett Jennifer H. , Bishop Timothy , Northwood Emma L. , Smith Gillian , Wilkie Murray J.V. , Steele Robert J.C. , Carey Francis A. , Key Tim J. , Wolf Roland , Forman David
Published: September 2008

Epidemiologic evidence suggests a role for folate, a critical component of the 1-carbon cycle, in colorectal adenoma and cancer pathogenesis. Low folate levels, along with genetic polymorphisms in key enzymes such as methylene tetrahydrofolate reductase (MTHFR), can cause DNA hypomethylation and aberrant CpG methylation, which have been associated with colorectal tumor development. We investigated self-reported folate and alcohol intake alongside possible modifying effects of MTHFR 677 C>T and 1298 A>C polymorphisms in UK case-control studies of colorectal adenoma (317 cases, 296 controls) and cancer (500 cases, 742 controls). A significant association between MTHFR 1298 and colorectal cancer risk was observed [odds ratio, 1.57; 95% confidence interval (95% CI), 1.05-2.37], which was more pronounced in males (odds ratio, 3.02; 95% CI, 1.63-5.62). Although we found no association between MTHFR 677 and colorectal cancer, when data were stratified by sex, an increased risk was seen in females (odds ratio, 1.96; 95% CI, 1.11-3.46) but not in males. High folate intake was associated with a decreased risk for colorectal adenoma (odds ratio, 0.47; 95% CI, 0.30-0.73; Ptrend, <0.001), which was modified by MTHFR 1298 genotype (Pinteraction = 0.006). However, we found no evidence to support the hypothesis that a high-folate diet protects against colorectal cancer development. Consistent with previous studies, high alcohol intake (≥14 U/wk) was associated with a significantly increased cancer risk (odds ratio, 2.57; 95% CI, 1.81-3.64). Our data suggest that dietary folate intake may be an important determinant for premalignant colorectal disease development but not colorectal cancer, an association that is modified by MTHFR genotype. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2421–30)
Associations of Lifestyle and Physiologic Factors with Prostate-Specific Antigen Concentrations: Evidence from the National Health and Nutrition Examination Survey (2001-2004)
Authors: Parekh Niyati , Lin Yong , Marcella Stephen , Kant Ashima K. , Lu-Yao Grace
Published: September 2008

Studies suggest inverse associations between obesity and prostate-specific antigen (PSA). However, there is little evidence whether factors related to obesity, including lifestyle (diet and physical activity) and physiologic factors (insulin resistance and metabolic syndrome), influence PSA. We used dietary, physical activity, and serum PSA, insulin, glucose, and lipid data for men >40 years from the National Health and Nutrition Examination Survey (2001-2004; N = 2,548). Energy, fat, and carbohydrate intakes were estimated from a 24-hour dietary recall. Men were considered as having metabolic syndrome based on the Adult Treatment Panel III criteria. Leisure-time physical activity and doctor-diagnosed hypertension were self-reported. Body mass index was calculated from measured weight and height. We computed the geometric mean PSA (ng/mL), adjusted for age, race, and body mass index, by tertile of energy, fat, and carbohydrate intake and level of physical activity, and among men with and without insulin resistance and metabolic syndrome in the whole population and by race. The geometric mean PSA (95% confidence interval) among men in the lowest tertile of energy was 1.05 (0.97-1.1) relative to 0.85 (0.8-0.9) in the highest tertile (P = 0.0002) in the whole population. The PSA concentrations were lower among overweight men with higher versus lower energy intake (P = 0.001). The PSA concentrations in men with insulin resistance was lower [0.87 (0.8-0.9)] relative to men without insulin resistance [0.98 (0.9-1.1)] at P = 0.04. All associations were in similar directions within racial subgroups. No associations were observed between the other lifestyle and physiologic factors. Additional studies are required to confirm these results and to investigate the potential mechanisms that may explain these relationships. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2467–72)
Effects of Personal Characteristics on Serum CA125, Mesothelin, and HE4 Levels in Healthy Postmenopausal Women at High-Risk for Ovarian Cancer
Authors: Lowe Kimberly A. , Shah Chirag , Wallace Erin , Anderson Garnet , Paley Pamela , McIntosh Martin , Andersen M. Robyn , Scholler Nathalie , Bergan Lindsay , Thorpe Jason , Urban Nicole , Drescher Charles W.
Published: September 2008

Objective: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program.

Methods: We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 155 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels.

Results: In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03).

Conclusions: CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2480–7)
Sexually Transmissible Infections and Prostate Cancer Risk
Authors: Huang Wen-Yi , Hayes Richard , Pfeiffer Ruth , Viscidi Raphael P. , Lee Francis K. , Wang Yun F. , Reding Douglas , Whitby Denise , Papp John R. , Rabkin Charles S.
Published: September 2008

Background: Sexually transmissible infections (STI) have been variably associated with increased risks of prostate cancer, largely in case-control studies.

Methods: In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we examined risk of prostate cancer in relation to serum antibodies to Chlamydia trachomatis, human papillomavirus-16 and -18, herpes simplex virus-2, cytomegalovirus, and human herpesvirus-8 in 868 cases (765 Whites and 103 Blacks) and 1,283 controls matched by race, age, time since initial screening, and year of blood draw; all blood samples were collected at least 1 year before prostate cancer diagnosis, except for 43 Black cases. We also assessed risk associated with self-reported history of syphilis and gonorrhea.

Results: Prevalences of the 7 STIs among controls were weakly correlated, and all were more frequent among Blacks than Whites, except for human herpesvirus-8. Among Whites, prostate cancer risk was not significantly associated with the individual infections or with their number (Ptrend = 0.1); however, men with one or more STI had slightly higher risk (odds ratio, 1.3; 95% confidence interval, 1.0-1.6). Among Blacks, excess risk was associated with IgA antibody to C. trachomatis (odds ratio, 2.1; 95% confidence interval, 1.2-3.6).

Conclusion: This large prospective study of prostate cancer shows no consistent association with specific STIs and a borderline association with any versus none. Whether a shared response or correlated infection not directly measured underlies the weak association requires further study. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2374–81)
Construct Validity and Invariance of Four Factors Associated with Colorectal Cancer Screening across Gender, Race, and Prior Screening
Authors: McQueen Amy , Tiro Jasmin A. , Vernon Sally W.
Published: September 2008

Understanding individuals' perceptions of colorectal cancer screening (CRCS) is important for developing effective interventions to increase adherence to screening guidelines. Theory-based cognitive and psychosocial constructs have been associated with CRCS in the literature, but few studies have evaluated the psychometric properties of such measures. We hypothesized a correlated four-factor model, including CRCS perceived pros, cons, social influence, and self-efficacy. We also examined measurement invariance across subgroups based on gender, race (white; African American), and prior CRCS experience (never; overdue for repeat screening). We used baseline (n = 1,250) and 2-week (n = 1,036) follow-up survey data from participants in a behavioral intervention trial designed to increase CRCS. Only minor modifications were made to the hypothesized model to improve fit, and the final model was confirmed with a random half of the sample, as well as with follow-up data. Results support the hypothesized unidimensional construct measures and suggest that the items may be appropriate for all subgroups examined. Greater variance in responses to items assessing the perceived cons of CRCS was found among African Americans compared with whites, suggesting that race may moderate the association between perceived cons and CRCS in this sample. Pros, cons, social influence, and self-efficacy are associated with CRCS; therefore, using scales with known psychometric properties strengthens researchers' ability to draw conclusions about group differences and changes over time and to compare their results with other studies. Replication studies in other populations are needed to provide further evidence of construct validity for the scales reported here. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2231–7)
Family-Based Samples Can Play an Important Role in Genetic Association Studies
Authors: Lange Ethan M. , Sun Jielin , Lange Leslie A. , Zheng S. Lilly , Duggan David , Carpten John D. , Gronberg Henrik , Isaacs William B. , Xu Jianfeng , Chang Bao-Li
Published: September 2008

Over the past 2 decades, DNA samples from thousands of families have been collected and genotyped for linkage studies of common complex diseases, such as type 2 diabetes, asthma, and prostate cancer. Unfortunately, little success has been achieved in identifying genetic susceptibility risk factors through these considerable efforts. However, significant success in identifying common disease risk-associated variants has been recently achieved from genome-wide association studies using unrelated case-control samples. These genome-wide association studies are typically done using population-based cases and controls that are ascertained irrespective of their family history for the disease of interest. Few genetic association studies have taken full advantage of the considerable resources that are available from the linkage-based family collections despite evidence showing cases that have a positive family history of disease are more likely to carry common genetic variants associated with disease susceptibility. Herein, we argue that population stratification is still a concern in case-control genetic association studies, despite the development of analytic methods designed to account for this source of confounding, for a subset of single nucleotide polymorphisms in the genome, most notably those single nucleotide polymorphisms in regions involved with natural selection. We note that current analytic approaches designed to address the issue of population stratification in case-control studies cannot definitively distinguish between true and false associations, and we argue that family-based samples can still serve an invaluable role in following up findings from case-control studies. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2208–14)
Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse
Authors: Sakko Andrew J. , Butler Miriam S. , Byers Sharon , Reinboth Betty J. , Stahl Jürgen , Kench James G. , Horvath Lisa G. , Sutherland Robert L. , Stricker Phillip D. , Henshall Susan M. , Marshall Villis R. , Tilley Wayne D. , Horsfall David J. , Ricciardelli Carmela
Published: September 2008

The glycosaminoglycan chondroitin sulfate is significantly increased in the peritumoral stroma of prostate tumors compared with normal stroma and is an independent predictor of prostate-specific antigen (PSA) relapse following radical prostatectomy. In this study, we determined whether specific alterations in the sulfation pattern of glycosaminoglycan chains in clinically organ-confined prostate cancer are associated with PSA relapse. Immunoreactivity to distinct glycosaminoglycan disaccharide epitopes was assessed by manually scoring the staining intensity in prostate tissues from patients with benign prostatic hyperplasia (n = 19), early-stage cancer (cohort 1, n = 55 and cohort 2, n = 275), and advanced-stage cancer (n = 20). Alterations to glycosaminoglycans in benign and malignant prostate tissues were determined by cellulose acetate chromatography and high-pressure liquid chromatography. Glycosaminoglycan disaccharide epitopes were localized to the peritumoral stroma of clinically localized prostate cancer. The level of immunostaining for unsulfated disaccharides (C0S) in the peritumoral stroma, but not for 4-sulfated (C4S) or 6-sulfated disaccharides (C6S), was significantly associated with the rate of PSA relapse following radical prostatectomy. High levels of C0S immunostaining were determined to be an independent predictor of PSA relapse (1.6-fold, P = 0.020). Advanced-stage prostate cancer tissues exhibited reduced electrophoretic mobility for chondroitin sulfate and increased unsulfated disaccharides when compared with benign prostatic hyperplasia tissues, whereas the sulfated disaccharide levels were unaffected. The level of C0S immunostaining in the peritumoral stroma is an independent determinant of PSA failure in clinically localized prostate cancer. Specific alterations to chondroitin sulfate side chains occurring during tumor development may be a crucial step for disease progression in prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2488–97)
Plasma Alkylresorcinols and Urinary Alkylresorcinol Metabolites as Biomarkers of Cereal Fiber Intake in Finnish Women
Authors: Aubertin-Leheudre Mylène , Koskela Anja , Marjamaa Annukka , Adlercreutz Herman
Published: September 2008

Alkylresorcinols (AR) could be good biomarkers of consumption of fiber-rich cereal products. The aim of this study was to examine the relationship between plasma ARs or urinary AR metabolites and cereal fiber intake in women consuming their habitual diet. Twenty-five postmenopausal and 31 premenopausal women were recruited. The subjects included also vegetarians (n = 20) to obtain a broad range of cereal intake. Dietary intake, plasma ARs, and urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid] were measured. Pearson's and Partial correlation tests were done between dietary fiber intake and plasma ARs or urinary AR metabolites. Cereal fiber intake correlated significantly with plasma AR C17:0 (r = 0.387), AR C19:0 (r = 0.350), AR C21:0 (r = 0.428), AR C23:0 (r = 0.409), AR C25:0 (r = 0.283), and total AR (r = 0.406) and with urinary AR metabolites DHBA (r = 0.359) and DHPPA (r = 0.402) even after adjustment for body mass index and age, which could be confounding variables. This is the first study to show a significant correlation between plasma ARs or urinary AR metabolites and cereal fiber intake during consumption of a habitual diet. These results indicate that assay of plasma ARs or urinary AR metabolites may be used as biomarkers in epidemiologic studies in free-living populations to evaluate the role of cereal fiber intake in various diseases. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2244–8)
Myeloperoxidase-Positive Cell Infiltration in Colorectal Carcinogenesis as Indicator of Colorectal Cancer Risk
Authors: Roncucci Luca , Mora Erika , Mariani Francesco , Bursi Serena , Pezzi Annalisa , Rossi Giuseppina , Pedroni Monica , Luppi Davide , Santoro Luisa , Monni Sebastiano , Manenti Antonio , Bertani Angela , Merighi Alberto , Benatti Piero , Di Gregorio Carmela , Ponz de Leon Maurizio
Published: September 2008

Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in ×100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean ± SD, 2.7 ± 2.0 versus 1.4 ± 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 ± 15.5 versus 11.9 ± 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2291–7)
Repair of UV Dimers in Skin DNA of Patients with Basal Cell Carcinoma
Authors: Segerbäck Dan , Strozyk Malgorzata , Snellman Erna , Hemminki Kari
Published: September 2008

Epidemiologic studies suggest that exposure to sunlight is the primary etiologic agent for basal cell carcinoma. Formation of UV-induced DNA damage is believed to be a crucial event in the process leading to skin cancer. In this study, repair of photoproducts in DNA was followed in the skin of patients with basal cell carcinoma and control subjects. The subjects were exposed to 800 J/m2 Commission Internationale de 1'Éclairag of solar-simulating radiation on buttock skin. Biopsies were taken at 0 hour, 24 hours, and 3 weeks after the exposure. Two cyclobutane pyrimidine dimers, TT=C and TT=T, were measured using a sensitive 32P-postlabeling assay. Initial levels of both TT=C and TT=T differed between individuals in both groups. The levels of TT=T in patients with basal cell carcinoma and controls were similar (9.9 ± 4.0 and 9.2 ± 2.9 products per 106 normal nucleotides), whereas the level of TT=C was significantly lower in controls than in patients with basal cell carcinoma (6.2 ± 3.1 versus 10.9 ± 4.5 products per 106 normal nucleotides). The fractions of TT=T remaining after 24 hours and 3 weeks were significantly higher in patients with basal cell carcinoma (72% and 11%) compared with controls (48% and 5%). A slower removal in patients with basal cell carcinoma than in controls was indicated also for TT=C (52% versus 42% remaining at 24 hours); however, the difference between groups was not significant. When including data from our previously reported small-scale study, the fraction of dimers remaining at 24 hours was significantly higher in patients with basal cell carcinoma for both TT=C and TT=T. The data suggest that patients with basal cell carcinoma have a reduced capacity to repair UV-induced DNA lesions. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2388–92)
Age and Severity of Mucosal Lesions Influence the Performance of Serologic Markers in Helicobacter pylori–Associated Gastroduodenal Pathologies
Authors: Camorlinga-Ponce Margarita , Flores-Luna Lourdes , Lazcano-Ponce Eduardo , Herrero Rolando , Bernal-Sahagún Fernando , Abdo-Francis Juan Miguel , Aguirre-García Jesús , Muñoz Nubia , Torres Javier
Published: September 2008

Objective: The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non–atrophic gastritis, preneoplastic lesions, and gastric cancer.

Methods: We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay.

Results: We included 618 patients, 368 with non–atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non–atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA.

Conclusions: This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2498–504)
Genetic Polymorphisms of the E-Cadherin Promoter and Risk of Sporadic Gastric Carcinoma in Chinese Populations
Authors: Zhang Baozhen , Pan Kaifeng , Liu Zhaojun , Zhou Jing , Gu Liankun , Ji Jiafu , Ma Junling , You Wei-cheng , Deng Dajun
Published: September 2008

Frequent mutations and loss of expression of E-cadherin have been reported in a number of cancers. E-cadherin germ line mutations lead to a high risk of familial diffused gastric carcinoma. In the present study, to evaluate the effect of genetic polymorphisms in the E-cadherin promoter on the risk of sporadic gastric carcinoma (SGC), a comprehensive study was conducted in two populations with high and low risk of SGC in China, respectively. Five hundred seventy-two SGC cases and 625 controls from low-risk area and 589 individuals enrolled in a long-term follow-up survey in high-risk area were studied. Polymorphisms of E-cadherin around transcription start site (−437 to +314) were analyzed by sequencing. Five variations of −347del>A, −160C>A, −73A>C, +178T>C, and +234 13N ins>del were linked tightly. The −347del/del and its strongly linked +178T/T, +234 13N ins/ins genotypes increased male SGC risk in the high-risk area significantly [odds ratio (OR), 2.22; 95% confidence intervals (95% CI), 1.10-4.46] and correlated with the severity of gastric lesions. A synergetic effect was also observed between −347del/del genotype and Helicobacter pylori infection (OR, 4.93; 95% CI, 1.65-14.71). Compared with −347del-containing haplotypes, the −347A-containing haplotype [A(−347)-C(−160)-A(−73)-C(+178)-13N del(+234)] decreased the risk of SGC among male subjects (OR, 0.61; 95% CI, 0.37-1.01). Such correlation could not be observed among subjects from the low-risk area. The present data suggest that the −347del allele of E-cadherin strongly links with the +178T and +234 13N ins alleles. The −347del/del genotype may increase the susceptibility of SGC among males in the high-risk area of China. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2402–8)
Residential Traffic Density and Childhood Leukemia Risk
Authors: Behren Julie Von , Reynolds Peggy , Gunier Robert B. , Rull Rudolph P. , Hertz Andrew , Urayama Kevin Y. , Kronish Daniel , Buffler Patricia A.
Published: September 2008

Background: Exposures to carcinogenic compounds from vehicle exhaust may increase childhood leukemia risk, and the timing of this exposure may be important.

Methods: We examined the association between traffic density and childhood leukemia risk for three time periods: birth, time of diagnosis, and lifetime average, based on complete residential history in a case-control study. Cases were rapidly ascertained from participating hospitals in northern and central California between 1995 and 2002. Controls were selected from birth records, individually matched on age, sex, race, and Hispanic ethnicity. Traffic density was calculated by estimating total vehicle miles traveled per square mile within a 500-foot (152 meter) radius area around each address. We used conditional logistic regression analyses to account for matching factors and to adjust for household income.

Results: We included 310 cases of acute lymphocytic leukemias (ALL) and 396 controls in our analysis. The odds ratio for ALL and residential traffic density above the 75th percentile, compared with subjects with zero traffic density, was 1.17 [95% confidence interval (95% CI), 0.76-1.81] for residence at diagnosis and 1.11 (95% CI, 0.70-1.78) for the residence at birth. For average lifetime traffic density, the odds ratio was 1.24 (95% CI, 0.74-2.08) for the highest exposure category.

Conclusions: Living in areas of high traffic density during any of the exposure time periods was not associated with increased risk of childhood ALL in this study. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2298–301)