bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4431: NFATc1 silencing increases sensitivity of pancreatic cancer cells to phosphosulindac
Authors: Murray Onika T. , Vrankova Kvetoslava , Johnson Francis , Rigas Basil
Published: August 2012

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. Current chemotherapeutic agents have limited efficacy and play a minor role in its treatment. We previously determined that the novel agent phosphosulindac (P-S) significantly prevents colon cancer and have now extended our studies into pancreatic cancer. Microarray data demonstrated a 5-fold increase in the gene expression of Nuclear Factor of Activated T-cells (NFAT) in MIA PaCa-2 cells after 2 h of treatment with P-S. NFATc1 and NFATc2 isoforms have been shown to be up-regulated in pancreatic cancer. To determine the role NFATc1 played in response to treatment with our compound, we developed a NFATc1 shRNA model in BxPC-3 and GFP positive MIA PaCa-2 cells, and a NFATc1 overexpression model in GFP labeled MIA PaCa-2 cells. Knockdown of NFATc1 expression by shRNA was confirmed by western blot and qRT-PCR. A 2-fold decrease in IC50 of P-S was observed in NFATc1 shRNA cells. In contrast, overexpression of NFATc1 increased the IC50 of P-S by 1.2-fold. The ability of our compound to reduce cell viability more potently in NFATc1 shRNA cells prompted us to assess the effect of the protein on tumor growth in a MIA PaCa-2 xenograft. 5-6 week old female BALB/c nude mice were subcutaneously injected with NFATc1 wt, knock-down, and overexpression GFP labeled MIA PaCa-2 cells. Animals were treated for 5 weeks, euthanized and tumor volume assessed. We observed a 50% reduction in tumor volume in NFATc1 wt, 63% reduction in NFATC1 knock-down, and a 26% reduction in NFATc1 overexpression xenograft. NFATc1 localization is indicative of its activity, with nuclear localization being the active form. We assessed OCT-embedded sections of our xenograft tissue to determine the localization of NFATc1 in GFP labeled tumor cells. Confocal microscopy data showed that in comparison to control, P-S treated tissue demonstrated decreased nuclear localization of the protein, indicating that P-S may suppress the activation of NFATc1. We observed a similar trend in NFATc1 knock-down and overexpression tissue, though our compound demonstrated a greater effect on tumor reduction in NFATc1 knock-down mice. We conclude that P-S is a potentially important agent for the treatment of pancreatic cancer and that our compound may play a role in NFATc1 localization and activation.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4431. doi:1538-7445.AM2012-4431
Abstract 444: MACC1 as biomarker for progression and prognosis of human malignant glioma
Authors: Stein Ulrike S. , Fuchs Steffen , Monoranu Camelia M. , Herrmann Pia , Smith Janice , Ernestus Ralf-Ingo , Vince Giles H. , Hagemann Carsten
Published: August 2012

Metastasis-associated in colon cancer-1 (MACC1) is a prognostic indicator for metastasis formation and metastasis-free survival of colon cancer patients. Patients with low MACC1 expressing primary tumors had a 5-year-survival of 80%, whereas subjects with high MACC1 expressing tumors had a 5-year-survival of only 15%. Correlations of MACC1 expression levels with tumor progression, recurrence and metastasis have meanwhile been reported for e.g. gastric, lung and hepatocellular cancer. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) are the most prevalent brain tumors of adults either developing de novo without known precursor-lesion (primary GBM), or progressing from low grade astrocytomas (secondary GBM). Patients suffering from GBM have a very disadvantageous prognosis. Although these tumors rarely metastasize, they are characterized by rapid growth, and their invasive and migratory behavior is similar to those of metastatic cells of tumors with different origin. Therefore we tested our hypothesis on MACC1 involvement in progression of human gliomas. MACC1 mRNA expression increased concomitantly with increasing WHO grading, as demonstrated by semi-quantitative and quantitative RT-PCR of biopsies from human low grade astrocytomas and GBM. MACC1 protein expression allowed discrimination of dormant and recurrent LGA and of primary and secondary GBM, as shown by immunohistochemistry of an independent patients’ cohort. Furthermore, strong MACC1 expression was associated with reduced median patients’ survival. Finally, we performed real-time measurements of migration and proliferation in the MACC1-transfected GBM cell line U138/MACC1 and found promoted proliferation and migration. Therefore, MACC1 may be a new biomarker for progression and for prognosis of human malignant gliomas and might represent a new potential therapeutic target for inhibition of their proliferation and migration.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 444. doi:1538-7445.AM2012-444
Abstract 4445: Defining a pipeline to use next generation sequencing for genetic testing in hereditary cancer
Authors: Lazaro Conxi , López-Doriga Adriana , Castellsagué Ester , del Valle Jesús , Tornero Eva , Moreno Víctor , Pineda Marta , González Sara , Feliubadaló Lídia , Capellá Gabriel
Published: August 2012

One of the emerging Next Generation Sequencing (NGS) applications is amplicon resequencing, which can be applied to screen for mutations in defined genes with diagnostic value. However, in this scenario, methods and protocols are still poorly developed. To address this need, we have established a study workflow that integrates experimental work and bioinformatics analyses. Our Unit of Genetic Testing for Hereditary Cancer is using kits for Multiplex Amplification of Specific Targets for Resequencing (MASTR) from the Multiplicom Company in order to generate highly homogeneous gene specific libraries for point mutation detection. Currently we have completed a proof of concept for the Breast Cancer Susceptibility kit (BRCA1 and BRCA2). We analysed a training set of 267 variants in 28 samples, and a validation set of 137 variants in 14 samples. Results from the GS Junior were combined with those resulting from the analysis of the homopolymer sequences in each gene. Sanger confirmation was performed in all the identified DNA variants. Low coverage (<=38x; 1.2% of the target) regions were also Sanger sequenced. The bioinformatics analysis combined the Variant Identification Pipeline software (VIP, De Shrijver, JM et al. BMC Bioinformatics 2010) together with a set of in-house designed R scripts in order to obtain both a Coverage Report as well as a Variant Calling Report. The first training set of 28 samples showed a sensitivity and specificity of 97.6% and 100%, respectively. After the improvement of the kit and the analysis pipeline, the validation set of 14 samples demonstrated an excellent specificity and sensitivity of the pipeline (100% both). In conclusion, we showed that a combined algorithm both at the experimental as well as at the bioinformatics level allows the interpretation of NGS results with a good specificity and sensitivity for diagnosis purposes. We are now finishing our proof of concept for genes responsible for Hereditary Colorectal Cancer, results will be presented at the meeting. This work has been supported by Spanish Ministry of Science and Innovation, Carlos III Health Institute ISCIII (RD06/0020/1050; RD06/0020/1051; PI10/01422; CA10/01474); The Government of Catalonia (2009SGR290) and The Spanish Association Against Cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4445. doi:1538-7445.AM2012-4445
Abstract 4447: In search of the ideal cancer screening test
Authors: Pivot Xavier , Viguier Jérôme , Morère Jean-François , Blay Jean-Yves , Coscas Yvan , Roussel Claire , Eisinger François
Published: August 2012

Background: The success of a cancer screening program partly depends on the compliance level of the screened population for the proposed screening procedure. Since 2005, EDIFICE surveys on cancer screening behaviours are carried out in France in the general population for breast, colon and prostate cancers. In the third edition of the EDIFICE surveys, subjects were questioned on what could be improved on screening tests. Methods: This third nationwide observational study, EDIFICE 3, was conducted through phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years, using the quota method, from July 8th to July 28th, 2011. The question concerning subjects’ expectations for a screening test was: “If scientific progress were made, what kind of cancer screening test would you wish to be proposed?” Results: For breast cancer screening, among 669 women never treated for cancer, the main expectations were: a more reliable imaging or radiological test for 43% of the subjects, a blood test for 32% and no preference for 17% of the subjects. For colon cancer screening, among 1469 subjects never treated for cancer, the main expectations were: a blood test for 35% of the subjects, no preference for 22% and a more reliable imaging or radiological test for 21% of the subjects. Results show a low level of satisfaction for the fecal occult blood test with 9% of the subjects looking for a more reliable fecal test. For prostate cancer screening, among 711 men never treated for cancer, the main expectations were: a blood test for 43% of the subjects, a more reliable imaging or radiological test for 21% and no preference for 21 % of the subjects. Conclusions: For breast cancer and prostate cancer, screening procedures are well accepted by the population. The vast majority prefers a blood test for cancer screening, even if they seem to accept radiological tests. In contrast, the population seems reluctant with fecal occult blood tests. This suggests the need to think over colon cancer screening tests to improve their results.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4447. doi:1538-7445.AM2012-4447
Abstract 4451: The NCI Early Detection Research Network (EDRN) urinary PCA3 validation trial
Authors: Wei John Thomas , Sanda Martin G. , Thompson Ian M. , Partin Alan , Feng Ziding , Sokoll Lori , Groskopf Jack , Brown Elissa , Lotan Yair , Kibel Adam , Lin Daniel , Taneja Samir , Viterbo Rosalia , Busby Erik , Bidair Mohamed , Kagan Jacob , Srivastava Sudhir
Published: August 2012

INTRODUCTION: Widespread use of PSA screening has raised concerns of overdiagnosis of low risk and underdiagnosis of high grade cancer. This is primarily due to the low sensitivity and specificity of PSA. PCA3, a non-coding large chain ribonucleic acid, is significantly over-expressed in cancer tissue and quantitatively measured by a novel urinary assay. The objective of this NCI EDRN trial was to conduct a comprehensive, independent validation of the PROGENSA PCA3 Assay for the detection of prostate cancer. METHODS: A prospective, PROBE-compliant NCI validation trial was undertaken at 11 clinical sites to evaluate PCA3 positive predictive value (PPV, PCA3 score >60) in the initial biopsy setting and negative predictive value (NPV, PCA3 score <20) in the repeat biopsy setting. PCA3 was obtained prior to biopsy but following an attentive DRE. We hypothesized that PPV for an initial prostate biopsy to be at least 55% and that NPV for a repeat biopsy to be at least 75%. The accuracy of PCA3 in detecting any prostate cancer and secondarily, high grade cancer (Gleason > 7), was compared to PCPT risk calculator through ROC curve analysis. RESULTS: 880 eligible men (mean age 62 years) were enrolled; 305 had a prior negative prostate biopsy. 99% had an informative PCA3 test. For the detection of any cancer, PPV was 80% (95% CI: 0.72 - 0.86) in the initial biopsy group while NPV was 88% (95% CI: 0.81 - 0.93) in the repeat biopsy group. PCA3 performance was superior to PCPT risk estimation and improved upon the detection of any cancer (p<0.006) and high grade cancer (p<0.02) when combined with the PCPT risk model. CONCLUSIONS: PCA3 ability to detect prostate cancer was superior to PCPT risk calculator in both the initial (p < 0.0001) and repeat biopsy setting (p=0.001)Independent validation of PCA3 demonstrated a high PPV in the initial biopsy setting and a high NPV in the repeat biopsy setting. Given the significant improvements in risk estimation over PCPT, PCA3 is expected to greatly enhance clinical decision making.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4451. doi:1538-7445.AM2012-4451
Abstract 4452: Mother-daughter communication and breast cancer prevention knowledge, attitudes, and behaviors between Hispanic and non-Hispanic college women
Authors: Kratzke Cynthia , Vilchis-Licon Hugo
Published: August 2012

Background: Although breast cancer prevention programs focus primarily on women ages 40 and older, little is known about breast cancer prevention awareness among young women. Cancer communication is essential for early detection and treatment for Hispanic and non-Hispanic women. Data trends show Hispanic women are more likely to be diagnosed with more advanced stages of breast cancer at an early age. Aim: The purpose of this exploratory study is to examine mother-daughter communication and breast cancer prevention knowledge, attitudes, and breast self-examination (BSE) behaviors between Hispanic and non-Hispanic college women. Method: Using a cross sectional study design, a convenience sample of college women ages 18 and older were surveyed in Fall 2010 at a southwestern university. Survey items were developed using the Health Belief Model framework. An open-ended item was included to elicit descriptions of breast cancer prevention advice received from their mothers. Results: Self-reported data were obtained from 71 college women (44% Hispanic and 56% non-Hispanic) ages 18 to 49 with a mean age of 22.6 (SD = 5.6). Overall, 33% received mother-daughter communication about breast cancer prevention, 80% received a provider's recommendation to conduct BSE, and 62% conducted BSE. Nearly 74% knew someone with breast cancer. Bivariate analysis revealed no significant differences for mother-daughter communication, knowledge, and self-efficacy for breast cancer prevention. In content analysis, only non-Hispanic college women received advice from their mothers about modifiable risk factors for breast cancer prevention. Hispanic college women (84%) were more likely compared to non-Hispanic women (63%) to have friends who supported BSE (p=.023). In addition, Hispanic college women (61%) were more likely compared to non-Hispanic women (38%) to seek online breast cancer information (p=.023). Conclusion: Our preliminary findings support the need for college educational breast cancer prevention programs including risk factors. Future research is suggested with a larger sample size to validate findings as well as to explore Internet use to seek quality online health information with an emphasis on breast cancer prevention information.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4452. doi:1538-7445.AM2012-4452
Abstract 4453: Smoking characteristics, intention to quit, and nicotine dependence in patients with head and neck cancer
Authors: Conlon Michael S.C. , Saunders Deborah P. , Meigs Margaret L. , Allemano Justin A. , Bewick Mary A.
Published: August 2012

There are high rates of smoking among head and neck cancer patients, and successful smoking cessation may offer a treatment and survival benefit for these patients. This prospective study was designed to assess baseline smoking characteristics, and intention to quit in a cohort of patients with head and neck cancer. All patients attended the dental oncology clinic within the regional cancer centre for assessments before, during, and after primary treatment. Primary treatment included one or more of radiation therapy, chemotherapy, or surgery. Participation in this study was offered to ever smokers (defined as having smoked at least 100 cigarettes in their lifetime), and involved completing a questionnaire that assessed baseline smoking related behaviours, including nicotine dependence using the Fagerstrom Test for Nicotine Dependence (FTND), and intention to quit smoking. Patients were asked for consent to provide a saliva sample for genetic analyses and for future contact to assess smoking cessation and other health-related outcomes. Personalised counselling about smoking cessation, by trained staff, was also offered. One hundred and eleven consecutive patients have agreed to participate. Most (77 %) are male, with a median age of 65 years (range 36-92 years). Participants reported a median of 37 pack-years of smoking, and 43% were nicotine dependent (FTND score indicating high or very highly dependent). Nicotine dependence level was significantly associated with smoking status at enrolment, with current smokers more likely to report significantly higher nicotine dependence levels than those who were not smoking (p=0.03). While 96% (n=104) of the participants had previously attempted smoking cessation, 35% (n=39) were current smokers at study enrolment. Most of the current smokers (80%) were interested in quitting smoking and in receiving personalized counselling for cessation. This study demonstrates the need to support cessation efforts in this population of cancer patients, and highlights the role of nicotine dependence and smoking behaviour. Future research into smoking cessation methods, including the role of genetic variants in nicotine dependence and cessation, may help us better address smoking behaviours in cancer patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4453. doi:1538-7445.AM2012-4453
Abstract 4455: Mild and moderate early-life stressors differentially affect stress reactivity and mammary tumorigenesis in BALB/c mice: A new look at the stress and breast cancer relationship
Authors: Kerr Leslie R. , Boyd Allison , Heighton Ryan , Munro Meagan , Salleh Ayesha
Published: August 2012

Many studies have produced inconsistent support for the hypothesized role of stressful life events in breast cancer risk. One major factor contributing to the inconsistent data could be that differences in premorbid physiological (e.g., endocrine levels) and psychological (e.g., emotional reactivity to challenges) characteristics were not taken into account and therefore, nor was the enduring impact of these differences on many aspects of endocrine activity and mammary gland development. It is difficult to gain information on human childhood variables that affect breast development and even more still on the influence of those variables into adulthood. Thus, evidence for factors influencing breast development and increased cancer risk during this time is limited. To this end, we use an established rodent model in which mild and moderate chronic neonatal stressors of brief and long maternal separation (BMS and LMS, respectively) over the first 3 weeks of life cause enduring functional changes to limbic-pituitary-adrenal axis activity. With this model, we show that BMS and LMS experiences differentially alter emotion- and stress-related behaviors of adult female BALB/c offspring. Circulating, corticosterone (CORT) and estrogen (E2) levels were also differentially altered by the BMS and LMS experiences as were transcript or protein levels of estrogen receptor (ER)α and ERα in ‘normal’ mammary glands. Interestingly, increased mammary tumorigenesis in LMS mice following adulthood carcinogen (7,12-dimethylbenz[α]anthracene; DMBA) administration was related to lower circulating plasma CORT and E2 levels, higher ERα protein (but not transcript), and lower ERα transcript (but not protein) levels in mammary glands. We suggest that early-life physical and psychosocial environments influence breast cancer risk by shaping the behavioral phenotype and altering circulating hormone levels which in turn alter the cellular and molecular architecture of the breast predisposing some to increased risk of carcinogenesis. A better understanding of the biobehavioral pathways that govern the complex interplay among environment, phenotype, and normal and malignant breast development will facilitate the creation of effective behavioral and cellular strategies for cancer prevention.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4455. doi:1538-7445.AM2012-4455
Abstract 4458: The burden of cancer in Japan
Authors: Koinuma Nobuo
Published: August 2012

Objectives: The burden of cancer to society is growing significantly in terms of human suffering and cost. The burden of cancer in Japan is projected to grow due to the tendency of the morbidity and mortality to increase and the technical progress in treatment. The problem of the patients who cannot undergo required cancer care due to economic reasons has been increasing rapidly. In our universal health insurance system, patients are responsible for 10-30% copayments for medical services, and there is a ceiling on copayments set most recently at $970 per month for middle-income families. However, patients still have a considerable economic burden and it is critical to cope with the problem adequately so that all patients have access to appropriate and up-to-date care. Methods: We surveyed the actual situation of the burden of patients on a national scale. We asked patients to tabulate their concrete expenses in connection with cancer care in a questionnaire by looking at receipts and a household account book. We also conducted the survey for their attending physicians. Results: The annual out-of-pocket expenses including direct and indirect expenses were an average of $11,200, and the refund mostly from the private insurance benefits was $7,000 (n= 6,604; 63.3 years old) on average. The balance ($4,200) is their real expenses. The out-of-pocket expenses in molecular-targeted therapy and in heavy ion cancer treatment were $13,400 (n=1,032) and $46,700 (n=388) respectively. The expenses differ by the lesion and stage of cancer and the treatment. For example, in case of colon cancer the expenses in stage 3 and stage 4 were $10,900 (n=59) and $18,300 (n=77) respectively. The mean and median of the expenses for trastuzumab (n=199) were $10,600 and $9,800 and those for bevacizumab (n= 144) were $14,200 and $12,500 respectively. The 34% patients with colon cancer were between $11,100 and $ 33,300 in their household income and 39% were below $ 77,800 in their savings (n= 223). 62% of those had to withdraw the savings to pay the fee for medical services. 1.5 in-patients and 1.6 outpatients per month and per doctor had to change or discontinue the most appropriate treatment for economic reasons according to the survey for physicians. Conclusion: The burden of cancer is growing for both society and patients. The growth rate of the medical expenses of cancer care from 2000 to 2009 in Japan was 42.1%, more than three times the growth of the national medical expenditure. In order to deliver the high quality and equitable cancer care, it is important to discuss the cost with patients and to minimize the economic burden of patients in clinical settings through appropriate policy making.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4458. doi:1538-7445.AM2012-4458
Abstract 4459: Evaluation of the performance of a previous day recall of time spent in active and sedentary behaviors
Authors: Matthews Charles E. , Sampson Joashua , Keadle Sarah , Freedson Patty , Lyden Kate , Libertine Amanda , Fowke Jay H.
Published: August 2012

Previous-day recalls (PDR) collect information about time spent in specific active and sedentary behaviors, are presumed to be less error prone than traditional physical activity questionnaires, and therefore may be useful in epidemiologic studies of physical activity and cancer. Purpose. Evaluate the performance of a PDR for active and sedentary behaviors administered by phone by comparing it to a valid reference measure. Methods. Adolescents (n=91; 12-17 yrs; 53% female) and adults (n=88; 18-71 yrs; 55% female) wore an activPAL (aPAL) for 7 days to measure sedentary (sit/lie) and active time (standing/stepping) and completed up to three PDRs. Interviewers conducted PDRs eliciting open-ended reports of time spent sleeping and in specific active and sedentary behaviors. Bland-Altman methods and regression models evaluated PDR performance versus aPAL on matched days of observation. Mixed models were fit to quantify the error structure of the PDR using the following equation: PDRij = β0 + α1Tij + ri + eij, where Tij is the estimate of truth from aPAL and β1 is the slope of the regression of aPAL on PDR. Variances were estimated for systematic (≥ri) and random reporting errors (≥eij) for the PDR. Results. Adolescents and adults reported 10.0 (SD=2.2) and 9.9 (SD=2.8) hr/d of sedentary time, and 4.2 (SD=1.8) and 5.2 (SD=2.6) hr/d of active time, respectively. Total PDR active and sedentary time was greater than aPAL wear time (difference=0.58 hr/d, p0.05) negative bias for active time in adolescents (bias=−0.27 (SD=1.37) hr/d) and adults (bias=−0.13 (SD=1.44) hr/d). In contrast, a significant positive bias in PDR sedentary time was evident (p<0.01) in adolescents (bias=0.81 (SD=1.52) hr/d) and adults (bias=0.74 (SD=1.59) hr/d), in part due to greater PDR observation time. Reporting bias was unrelated to age (years), gender, or body mass index (BMI, kg/m2). Mixed models comparing PDR to aPAL indicated: (1) a strong linear relationship between measures for sedentary (≥1=0.90 to 1.00) and active time (≥1=0.70 to 0.95); (2) that reporting errors were predominantly random errors (≥ri < αeij); and (3) correlations between measures were high (Active: 0.54 to 0.73; Sedentary: 0.62 to 80) for these behavioral exposures. Conclusion. PDRs measuring active and sedentary behaviors rank-ordered individuals on the day observed, correlations with the reference measure were high, and systematic reporting errors were unrelated to age, gender or BMI. PDRs may have value in future epidemiological studies of physical activity and cancer. Support: R01NR011477; NCI Intramural Research Program

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4459. doi:1538-7445.AM2012-4459
Abstract 4460: Breast cancer knowledge and awareness among high school and college students in mid-Western USA
Authors: Mafuvadze Benford , Manguvo Angellar , He Jiaxin , Whitney Stephen D. , Hyder Salman M.
Published: August 2012

Breast cancer is the second leading cause of death in the United States among women. Each year approximately 200,000 new cases are reported and 40,000 women succumb to the disease. Early detection and treatment results in good prognosis and higher rates of patient survival; however, despite advanced methods of screening, breast cancer is often detected at an advanced stage when it has metastasized to other organs, particularly in younger, premenopausal patients who typically have a poor understanding of the disease. While educational activities meant to promote breast cancer awareness among women are conducted every year in the USA, especially during the month of October, previous studies show a widespread ignorance of the disease, in both the USA and in women around the world. At present there are no programs in place that specifically promote breast cancer awareness among high school and college students. Such programs would potentially engender the adoption and development of health habits likely to lead to early detection and treatment, including regular screenings and effective self-examination. The main goal of this study was to investigate breast cancer awareness among college and high school students. We used self-administered questionnaires to assess breast cancer perceptions and misconceptions, awareness of risk factors and understanding of breast self-examination. A total of 355 high school students and 132 college students in a Mid-Western area of the USA participated in the study. Our findings were in accordance with previous studies carried out in other regions of the world, showing that a high proportion of students at both high school and college level were largely ignorant of the risk factors associated with breast cancer. Furthermore, a number of misconceptions regarding the disease were common. Only 66% of female college students and 40% of female high school students reported having ever received information on breast self-examination. Interestingly, only half the students who had received instruction reported that they could perform breast self-examination with confidence. Most of the participants however, expressed an eagerness to have more information provided in schools. Consequently we strongly urge the adoption of more breast cancer awareness programs targeting college and high school students.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4460. doi:1538-7445.AM2012-4460
Abstract 4460A: Meat-related compounds and colorectal cancer risk by anatomical subsite
Authors: Miller Paige E. , Lazarus Philip , Lesko Samuel M. , Cross Amanda J. , Sinha Rashmi , Laio Jason , Zhu Jay , Harper Gregory , Muscat Joshua E. , Hartman Terryl J.
Published: August 2012

The most recent consensus statement issued by the World Cancer Research Fund and the American Institute for Cancer Research concluded that the evidence to support a positive association between intake of red and processed meat and colorectal cancer was convincing, yet the evidence for specific mechanisms explaining these associations remained inconclusive. To identify responsible compounds that may account for the previously observed statistical associations between meat and colorectal cancer, the present study examined associations between red meat, processed meat, and meat-derived heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), nitrites, and nitrates and colorectal cancer in a population-based case-control study in central and northeast Pennsylvania. This population is at particularly high risk for colorectal cancer compared to the U.S. as a whole (54.5/100,000 in PA versus 48.8/100,000 in the U.S. at the start of this study in 2007). Participants (989 colorectal cancer cases and 1,033 healthy controls) completed a 137-item food frequency questionnaire, the National Cancer Institute's (NCI) Diet History Questionnaire (DHQ), which included a meat module that was linked to a database of nitrites and nitrates. The meat module also allowed for the use of NCI's Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) software application to generate estimates of HCAs and PAHs. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat variables and colorectal cancer, stratified by anatomical subsite, were estimated from unconditional logistic regression models. After multivariable adjustment, there were no associations between red or processed meat and colorectal cancer. Nitrite plus nitrate intake was positively associated with proximal colon cancer (OR = 1.54, 95% CI = 1.03-2.31, P-trend = 0.025). A positive association was observed between 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal cancer (OR = 1.36, 95% CI = 1.02-1.82, P-trend = 0.027). Total mutagenic activity was positively associated with distal colon cancer (P-trend = 0.049). There was no association between benzo[a]pyrene and total colorectal cancer or any sub-site. These results indicate that HCAs, PAHs, nitrites, and nitrates may be risk factors for colorectal cancer, but additional studies that examine risk factors stratified by anatomical subsite are warranted.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4460A. doi:1538-7445.AM2012-4460A
Abstract 4463: Serum phytanic acid and prostate cancer risk: Results from a nested case-control study
Authors: Wright Margaret E. , Albanes Demetrius , Shi Fei , Moser Ann , Virtamo Jarmo , Gann Peter
Published: August 2012

Phytanic acid is a saturated branched chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. We measured phytanic acid as a percentage of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic acid were dairy fat, butter, and saturated fat (r=0.45, 0.42, and 0.40, respectively; all p-values <0.001). With the exception of lamb (r=0.18, p = 0.002), red meat intake was not significantly correlated with phytanic acid. There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models. However, a significant interaction between phytanic acid and baseline concentrations of beta-carotene was noted in relation to advanced disease (p-interaction = 0.04). Among men with lower beta-carotene levels, serum phytanic acid was suggestively associated with elevated risks of advanced prostate cancer (odds ratios and 95% confidence intervals for increasing phytanic acid tertiles = 1.0 (referent), 1.42 (0.78-2.59), and 1.80 (0.91-3.55); p trend = 0.08) whereas the opposite relationship was noted among participants with higher beta-carotene levels (for increasing phytanic acid tertiles, odds ratios and 95% confidence intervals = 1.0 (referent), 1.03 (0.52-2.06), and 0.59 (0.30-1.17); p trend = 0.06). Our findings indicate that serum phytanic acid may be associated with increased risks of advanced prostate cancer in men with low levels of the antioxidant beta-carotene.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4463. doi:1538-7445.AM2012-4463
Abstract 4468: Pre-diagnostic steroid hormone levels and risk of testicular germ cell tumors
Authors: McGlynn Katherine A. , Chia Victoria M. , Trabert Britton , Cook Michael B. , Quraishi Sabah , Stanczyk Frank Z. , Rifai Nader , Bradwin Gary , Rubertone Mark V. , Graubard Barry I. , Erickson Ralph L.
Published: August 2012

Background: Testicular germ cell tumors (TGCT), the most commonly occurring cancer among young men in the U.S., are thought to be endocrine-related tumors. The relationship between steroid hormone levels and development of TGCT, however, has been difficult to study given the rarity of the tumor in the general population and the paucity of pre-diagnostic serum from young men. The U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study, however, was able to overcome these obstacles by enrolling military servicemen who had previously donated serum specimens to the Department of Defense Serum Repository. Methods: STEED participants were enrolled between 2002 and 2005. The associations between TGCT risk and log-transformed serum concentrations of testosterone, free testosterone, estradiol, free estradiol, 3α-androstanediol glucuronide (3α-diol-G), an indicator of peripheral androgen action, and sex hormone-binding globulin (SHBG) were examined in 517 case and 790 control participants. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, adjusting for date of serum donation, age, race/ethnicity, family history of testicular cancer, history of cryptorchidism, height, and body mass index. Results: The analysis found that while testosterone was not significantly associated with TGCT risk, there was an inverse association between 3α-diol-G and risk (OR=0.80, 95%CI=0.63-0.99). In addition, there was a significant inverse association with TGCT and the ratio of 3α-diol-G to testosterone (OR=0.76, 95%CI=0.61-0.93). There was also a significant direct association between estradiol and TGCT risk (OR=1.41, 95%CI=1.06-1.87). The relationships between the free forms of testosterone and estradiol and risk were the same as the relationships between the total forms of each hormone and risk. There was no association between TGCT and SHBG. Conclusion: These results suggest that the hormone metabolism of men who subsequently develop TGCT may vary from that of other men. In men who develop TGCT, more testosterone may be converted to estradiol and less to dihydrotestosterone, the most potent form of androgen, than in men who do not develop TGCT. Further examination of metabolites, both upstream and downstream in the steroid hormone pathway, may help elucidate the mechanism by which these exposures are related to development of TGCT.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4468. doi:1538-7445.AM2012-4468
Abstract 4469: S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and colorectal adenoma risk
Authors: Shrubsole Martha J. , Wagner Conrad , Zhu Xiangzhu , Loukachevitch Lioudmila , Ness Reid M. , Zheng Wei
Published: August 2012

Introduction: Methionine and its metabolic derivatives regulate activity of most methyltransferases and activity of several enzymes involved in one-carbon metabolism. S-adenosylmethionine (SAM), the direct metabolite of methionine, is the methyl donor for nearly all methylation reactions in the body. SAM is irreversibly converted to S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine. SAH is a potent inhibitor of all methyltransferases. Very few studies have evaluated biological measures of methionine and its metabolites with colorectal cancer. Recently, a large cross-sectional study found plasma methionine was associated with a reduced risk of distal colorectal adenoma. To our best knowledge, no study has evaluated SAM or SAH with colorectal cancer or adenoma. Methods: In this study, we evaluated plasma levels of these markers with risk for colorectal adenoma using a colonoscopy-based matched case-control design. Participants were part of a large case-control study of colorectal adenoma. A subset of cases were individually matched to polyp-free controls in a 1:1 ratio on age, sex, race, study site and date of sample collection. Included in the analysis were 220 pairs of adenoma cases and polyp-free controls. SAM and SAH were measured in a single assay by high-performance liquid chromatography. Sex-specific quantile cutpoints were derived using the distributions among controls. Conditional logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations with colorectal adenoma risk after adjusting for age, and other potential confounders. All of the reported P values were two-tailed, and statistical significance was set at 0.05. Result: A statistically significant interaction between sex, SAH or SAM, and adenoma risk was observed. Among women, high SAH was associated with a borderline statistically significant increased risk of adenoma (p for trend=0.08). Among men, both high SAH (OR=0.36, 95% CI: 0.16-0.78, p for trend=0.009) and high SAM (OR=0.41, 95% CI: 0.19-0.88, p for trend=0.02) were associated with decreased risks of adenoma. The joint association of SAM and SAH was also evaluated among men. In comparison to men with low SAH and low SAM, men with high SAM and high SAH had a reduced risk of colorectal adenoma. Conclusion: The findings reported in this study are new, suggesting SAH and SAM may be involved in the development of colorectal adenoma. Further studies are warranted.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4469. doi:1538-7445.AM2012-4469
Abstract 4536: Identification of new prognostic biomarker of gastric cancer by systems analysis
Authors: Seol So-Young , Lim Jae Yun , Yoon Sun Och , Hong Soon Won , Kim Jong Won , Choi Seung Ho , Cho Jae Yong
Published: August 2012

Gastric cancer is one of the most common and cancer-related deaths worldwide and accounts for an estimated 800,000 deaths annually. Prognosis depends on the stage of disease. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. To differentiate the malignant potential appropriately, many efforts have been made to select prognostic markers. Molecular markers will be important in predicting patients’ outcomes and personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers which could be used to classify patients according to prognosis and also become new therapeutic targets. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. qRT-PCR and tissue microarray validated TXN overexpression and ERO1L have poor prognosis in gastric cancer. Finally, systems analysis revealed TXN family genes are highly correlated with many oncogene and tumor suppressor functional genes and shown relationship on energy and protein synthesis. Survival analysis based on Hierarchical-clustering of TXN family correlated mRNA expression genes revealed that TXN and TXNIP are significantly influenced the patient survival. We evaluated ERO1L and find out also significantly overexpressed in gastric tumor and suggest TXN family members are actively involved in gastric cancer. In vitro hypoxic experiment ERO1L was very highly expressed in hypoxic condition and this also supports TXN high expressed cancer cells are in hypoxic condition. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of TXN family and ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4536. doi:1538-7445.AM2012-4536
Abstract 4537: Tumoral expression on peroxisome proliferator-activated receptor ≤ is an independent prognostic marker in intestinal type of gastric cancer
Authors: Cho Soo-Jeong , Lee Jun Ho , Kook Myoung-Cheorl , Choi Il Ju , Ryu Keun Won , Kim Young-Woo
Published: August 2012

Introduction: Peroxisome proliferator-activated receptor ≤ (PPARδ) is a member of the nuclear hormone receptor family that regulates the expression of mediators of the inflammatory response. Metaplastic change secondary to chronic inflammation of gastric mucosa is regarded as a premalignant condition of intestinal-type gastric cancer (IGC). We aimed to evaluate the prognostic significance of PPARδ in IGC patients. Methods: The clinical significance of PPARδ was explored using tissue microarray methods and immunohistochemical staining of specimens from 306 IGC patients. The Kaplan-Meier method was used to calculate survival curves, and differences between the survival curves were assessed using the log-rank test. Cox proportional hazards regression was used to assess the effect of PPARδ expression on survival while controlling for other confounding covariates. Results: Among 306 patients with IGC (stage I-IV), PPARδ expression was detected by immunohistochemistry in the tumors of 209 (68.3%). The patients with PPARδ-positive tumors had significantly lower overall and gastric cancer-specific mortalities (P = 0.0010 and 0.0016, respectively, by the log-rank test) than did those with PPARδ-negative tumors. A positive PPARδ expression was a significant independent prognostic factor for gastric cancer-specific mortality by the Cox regression analysis in patients with IGC (adjusted hazard ratio, 0.42; 95% confidence interval, 0.22-0.81). The relationship between PPARδ and lower mortality was not modified by other clinical variables including tumor stage (all Pinteraction > 0.05). Conclusions: tumor expression of PPARδ was independently associated with lower mortality of patients with IGC. Keywords: Gastric cancer, Intestinal-type gastric cancer, Peroxisome proliferator-activated receptor ≤ (PPARδ), Prognostic marker, Survival

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4537. doi:1538-7445.AM2012-4537