http://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/591753.htmlThe Surveillance Epidemiology and End Results data demonstrate that the risk of non-Hodgkin lymphoma is lower for women, but that the incidence increases after fifty years of age, at which menopause is regularly reached, suggesting that female hormones may be protective for NHL. This study examines the influence of sex on lymphoma risk in a relevant large animal model. Records for dogs in the Veterinary Medical Database were analyzed from 1964 to 2002. Risk ratios were calculated to evaluate associations between sex, neutering status, and lymphoma occurrence. A total of 14,573 cases and 1,157,342 controls were identified. Intact females had a significantly lower risk of developing lymphoma, Odds Ratio 0.69 (0.63–0.74) with a P<.001. We conclude that there is a sex effect on NHL risk in dogs similar to humans. We hypothesize that the hormone levels of intact females lower the risk of NHL. The possibility of a protective role of endogenous estrogens in the etiology of NHL should be investigated.J. Armando Villamil, Carolyn J. Henry, Allen W. Hahn, Jeffrey N. Bryan, Jeff W. Tyler, and Charles W. Caldwell© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/242151.htmlIn a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.Alison L. Van Dyke, Michele L. Cote, Angela S. Wenzlaff, Judith Abrams, Susan Land, Priyanka Iyer, and Ann G. Schwartz© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/182521.htmlThere is uncertainty about risk heterogeneity for venous thromboembolism (VTE) in older patients with advanced cancer and whether patients can be stratified according to VTE risk. We performed a retrospective cohort study of the linked Medicare-Surveillance, Epidemiology, and End Results cancer registry in older patients with advanced cancer of lung, breast, colon, prostate, or pancreas diagnosed between 1995–1999. We used survival analysis with demographics, comorbidities, and tumor characteristics/treatment as independent variables. Outcome was VTE diagnosed at least one month after cancer diagnosis. VTE rate was highest in the first year (3.4%). Compared to prostate cancer (1.4 VTEs/100 person-years), there was marked variability in VTE risk (hazard ratio (HR) for male-colon cancer 3.73 (95% CI 2.1–6.62), female-colon cancer HR 6.6 (3.83–11.38), up to female-pancreas cancer HR 21.57 (12.21–38.09). Stage IV cancer and chemotherapy resulted in higher risk (HRs 1.75 (1.44–2.12) and 1.31 (1.0–1.57), resp.). Stratifying the cohort by cancer type and stage using recursive partitioning analysis yielded five groups of VTE rates (nonlocalized prostate cancer 1.4 VTEs/100 person-years, to nonlocalized pancreatic cancer 17.4 VTEs/100 patient-years). In a high-risk population with advanced cancer, substantial variability in VTE risk exists, with notable differences according to cancer type and stage.Isaac E. Hall, Martin S. Andersen, Harlan M. Krumholz, and Cary P. Gross© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/354257.htmlAdvances have been made in treatment and outcomes for pediatric cancer. However adolescents and young adults (AYAs) with cancer have not experienced similar relative improvements. We undertook a study to develop the methodology necessary for epidemiologic cancer research in these age groups. Our goal was to create the Kids, Adolescents, and Young Adults Cancer (KAYAC) project to create a resource to address research questions relevant to this population. We used a combination of clinic and population-based ascertainment to enroll 111 cases aged 0–39 for this methodology development study. The largest groups of cancer types enrolled include: breast cancer, leukemia, lymphoma, and melanoma. The overall participation rate is 69.8% and varies by age and tumor type. The study included patients, mothers, and fathers. The methods used to establish this resource are described, and the values of the resource in studies of childhood and young adult cancer are outlined.Nancy J. Link, Eva Maurer, Joan Largent, Erin Kent, Rebecca A. Morris, Leonard S. Sender, and Hoda Anton-Culver© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/302047.htmlRadiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation in oxidative stress-related enzymes may influence survival of rectal cancer patients. We hypothesized that genetic polymorphisms associated with higher amounts of reactive oxygen species (ROS) that exaggerate cytotoxic activity could improve survival after radiotherapy. We followed 114 rectal cancer patients who received radiotherapy for an average of 42.5 months. Associations between genotypes (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO and eNOS) and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. As hypothesized, patients carrying low ROS producing eNOS Glu298Asp asparagine allele showed an increased hazard of death compared to homozygous carriers of the glutamine allele (hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.01–4.38). However, carriers of low ROS producing MPO G463A A allele had a decreased hazard of death compared to patients homozygous for the G allele (HR: 0.44, 95% CI: 0.21–0.93) although patients homozygous for the A allele had a slightly increased hazard (HR: 1.12, 95% CI: 0.25–5.08). This explorative study provides first results and highlights the need for further, larger studies to investigate association between genetic variation in oxidative stress genes and survival of rectal cancer patients who received radiotherapy.Silvia Funke, Angela Risch, Alexandra Nieters, Michael Hoffmeister, Christa Stegmaier, Christoph M. Seiler, Hermann Brenner, and Jenny Chang-Claude© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/301973.htmlRetinoblastoma (Rb) is considered to represent the prototype of cancer linked to the sequential loss or inactivation of both alleles of a so-called “tumor suppressor gene”, the Rb1 gene. The pathogenetic mechanism behind this tumor was first hypothesized by Knudson in 1971 and further confirmed by others who identified the Rb1 gene whose loss or inactivation was claimed to be responsible for the disease. However, after about four decades of continuous research in the field of molecular biology, the evidence behind the role of the Rb1 gene in Rb appears to be seriously flawed in the light of epidemiological, biological, and clinical evidences. This editorial summarizes the inconsistencies on this subject. Nevertheless, the molecular biology establishment still adheres to the biased view of the genetic origin of Rb and other cancers, and hardly any alternative explanations are taken into account.Domenico Mastrangelo, Theodora Hadjistilianou, Sonia De Francesco, and Cosimo Loré© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/748367.htmlSeveral lifestyle factors play a significant role in determining an individual's risk of breast cancer. Many of them could be modified to protect against the malignancy. A nested case-control study was conducted to examine the association between selected lifestyle factors and non-BRCA-related breast cancer risk among French-Canadian women. Some 280 women with breast cancer and who were nongene carriers of mutated BRCA gene were recruited as cases. Another 280 women, without any cancer and nongene carriers of mutated BRCA gene served as controls. A tested lifestyle questionnaire was interviewer administered to incident cases to obtain information on weight history, smoking, physical activity, and other lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in logistic regression models. Comparing cases to controls, breast cancer risk was higher among subjects who reached their maximum body mass index (BMI) at an older age (>50 years) (OR=2.83; 95% CI: 2.34–2.91). A positive association was noted between breast cancer risk and weight gain of >34 lbs compared to weight gain of ≤15 lbs, since the age of 20 (OR=1.68; 95% CI: 1.10–2.58). Weight gain of >24 lbs compared to weight gain of ≤9 lbs, since the age of 30 also resulted in the same relationship (OR=1.96; 95% CI: 1.46–3.06). Similarly, since the age of 40, weight gain of >12 lbs compared to weight gain of ≤1 lb was associated with increased breast cancer risk (OR=1.91; 95% CI: 1.53–2.66). Women who smoked >9 pack-years of cigarettes had a 59% higher breast cancer risk (P=.05). Subjects who engaged in >24.8 metabolic-equivalent- (MET-) hours per week compared to ≤10.7 MET-hours per week of moderate physical activity had a 52% (P=.01) decreased risk and total physical activity between 16.2 and 33.2 MET-hours per week compared to ≤16.2 MET-hours per week, resulted in a 43% (P=.05) lower risk of breast cancer. In conclusion, weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect.Vishnee Bissonauth, Bryna Shatenstein, Eve Fafard, Christine Maugard, André Robidoux, Steven Narod, and Parviz Ghadirian© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2008/387423.htmlNonsynonymous SNPs (nsSNPs) in DNA repair genes may be important determinants of DNA damage and cancer risk. We applied a set of screening criteria to a large number of nsSNPs and selected a subset of SNPs that were likely candidates for phenotypic effects on DNA double-strand break repair (DSBR). In order to induce and follow DSBR, we exposed panels of cell lines to gamma irradiation and followed the formation and disappearance of γH2A.X foci over time. All panels of cell lines showed significant increases in number, intensity, and area of foci at both the 1-hour and 3-hour time points. Twenty four hours following exposure, the number of foci returned to preexposure levels in all cell lines, whereas the size and intensity of foci remained significantly elevated. We saw no significant difference in γH2A.X foci between controls and any of the panels of cell lines representing the different nsSNPs.Christina A. Markunas, David M. Umbach, Zongli Xu, and Jack A. Taylor© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2009/791754.htmlLynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes, MSH2 and MLH1. The aim of this study was to evaluate the age-dependent cancer risk in MSH2 or MLH1 mutation carriers from data of DNA diagnostic laboratories. To avoid overestimation, evaluation was based on the age-dependent proportion of mutation carriers in asymptomatic first-degree relatives of identified mutation carriers. Data from 859 such eligible relatives were collected from 8 centers; 387 were found to have inherited the mutation from their relatives. Age-dependent risks were calculated either using a nonparametric approach for four discrete age groups or assuming a modified Weibull distribution for the dependence of risk on age. Cancer risk was estimated starting at 28 (25–32 0.68 confidence interval) and to reach near 0.70 at 70 years. The risks were very similar for MSH2 and MLH1 mutation carriers. Although not statistically significant, the risk in males appeared to precede that for females by ten years. This difference needs to be investigated on a larger dataset. If confirmed, this would indicate that the onset of the colonoscopic surveillance may be different in male and female mutation carriers.Sylviane Olschwang, Kai Yu, Christine Lasset, Stéphanie Baert-Desurmont, Marie-Pierre Buisine, Qing Wang, Pierre Hutter, Etienne Rouleau, Olivier Caron, Violaine Bourdon, and Gilles Thomas© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2008/215809.htmlBoth genetic and epigenetic alterations characterize human nonsmall cell lung cancer (NSCLC), but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hypermethylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hypermethylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hypermethylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hypermethylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.Carmen J. Marsit, E. Andres Houseman, Heather H. Nelson, and Karl T. Kelsey© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2008/147905.htmlApoptotic capacity (AC) in primary lymphocytes may be a marker for cancer susceptibility, and functional single nucleotide polymorphisms (SNPs) in genes involved in apoptotic pathways may modulate cellular AC in response to DNA damage. To further examine the correlation between apoptotic genotypes and phenotype, we genotyped 14 published SNPs in 11 apoptosis-related genes (i.e., p53, Bcl-2, BAX, CASP9, DR4, Fas, FasL, CASP8, CASP10, CASP3, and CASP7) and assessed the AC in response to benzo[a]pyrene-7,8-9,10-diol epoxide (BPDE) in cultured primary lymphocytes from 172 cancer-free subjects. We found that among these 14 SNPs, R72P, intron 3 16-bp del/ins, and intron 6 G>A in p53, −938C>A in Bcl-2, and I522L in CASP10 were significant predictors of the BPDE-induced lymphocytic AC in single-locus analysis. In the combined analysis of the three p53 variants, we found that the individuals with the diplotypes carrying 0-1 copy of the common p53 R-del-G haplotype had higher AC values compared to other genotypes. Although the study size may not have the statistical power to detect the role of other SNPs in AC, our findings suggest that some SNPs in genes involved in the intrinsic apoptotic pathway may modulate lymphocytic AC in response to BPDE exposure in the general population. Larger studies are needed to validate these findings for further studying individual susceptibility to cancer and other apoptosis-related diseases.Zhibin Hu, Chunying Li, Kexin Chen, Li-E Wang, Erich M. Sturgis, Margaret R. Spitz, and Qingyi Wei© 2010, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/jce/2008/298495.htmlThe majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79), moderate (36), and severe (12) dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS)” (57) along with controls (69), in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.M. Singh, S. Mehrotra, N. Kalra, U. Singh, and Y. Shukla© 2010, Hindawi Publishing Corporation. All rights reserved.