bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A22: Sensitive detection of mutant KRAS in colorectal tissue using the multiplex QuARTS™ assay
Authors: Oldham-Haltom Rebecca , Leduc Christine , Hunt Oliver , Domanico Mike , Taylor William , Ahlquist David , Lidgard Graham
Published: June 2012

Background: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States, yet it is potentially the most treatable and preventable cancer with effective screening. Exact Sciences has developed a multi-biomarker CRC screening test that targets DNA methylation, DNA mutations, and hemoglobin in stool. The aim of this study was to evaluate the analytical accuracy of a novel assay for the detection of KRAS mutation sequences at Codons 12 and 13 in well-characterized colorectal tissues.

Methodology: A multiplexed KRAS assay was designed utilizing QuARTS (Quantitative Allele-specific Real-time Target and Signal amplification), a highly sensitive technology that combines allele-specific DNA amplification with invasive cleavage chemistry to generate signal during each amplification cycle similar to real-time PCR. The assay, which detects seven KRAS mutations and the reference gene β-actin, was used to assess 87 colorectal tissue samples (52 CRCs, 16 adenomas ≥ 1cm, and 19 normal epithelia) as determined by Mayo Clinic Pathology. Samples were obtained by microdissection of fresh frozen tissue biopsies. DNA was extracted by Mayo Clinic using a standardized chloroform/phenol methodology. The genotypes of each sample were established using dye terminator dideoxy sequencing in both the forward and reverse orientations. Copy numbers of KRAS mutations and β-actin were determined by conventional comparison against standard curves. KRAS data are reported as percent mutation and calculated by dividing mutant copies by β-actin copies and multiplying by 100.

Results: Based on sequencing data: the 52 CRC samples contained 22 KRAS mutations and 30 wild-type genotypes, the 16 adenomas ≥ 1cm contained 8 mutations and 8 wild-type genotypes, and the 19 normal tissues contained all wild-type genotypes. The QuARTS assay detected 100% of the KRAS mutations in the CRC and adenomas and provided excellent differentiation between wild-type and mutation, with the highest percent KRAS mutation of normal wild-type samples at 0.55% and the lowest percent mutation of KRAS positive samples at 8.34%. Based on this data, this assay has the potential to be more sensitive analytically than standard sequencing.

Conclusion: The QuARTS assay detects KRAS mutations in tissue with high sensitivity and specificity. This assay method could provide an accurate and high throughput approach to detection of KRAS mutations in biospecimens for multiple clinical applications.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A22.
Abstract A24: Evaluation and validation of biomarkers for prostate cancer early diagnosis
Authors: Reyes Niradiz , Bettin Alfonso , Causil Ceyla , Reyes Ismael , Geliebter Jan
Published: June 2012

Prostate cancer (PCa) remains the most frequently diagnosed malignancy in men and although effective treatment is possible for early stages, advanced PCa is largely incurable. PSA, the only relevant marker for this disease, has a low predictive value leading to unnecessary biopsies and associated complications. Thus, identification of better biomarkers able to accurately and reliably diagnose PCa at early stages is an important goal in prostate cancer research. Currently a number of potential biomarkers are being investigated as predictors of PCa diagnosis. Using quantitative real time PCR (qRT-PCR) we have analyzed in the PCa cell lines PWR-1E, LNCaP and PC3 the expression of a set of potential biomarkers previously identified by us in a microarray gene expression study. So far, we have found in these cell lines several differentially expressed genes, some of which encode extracellular matrix proteoglycans, cell adhesion molecules, genes related to motility, growth factor receptors, and tumor suppressor genes. We are in the process of evaluating these differentially expressed genes in cDNA panels of PCa at different disease stages and in prostate needle biopsy specimens taken from patients at diagnosis before any treatment have been established. The next step will be the validation, at the protein level in serum samples from a cohort of patients, of those genes showing an association to prostate cancer disease stages. A prospective clinical study will be necessary to confirm the clinical relevance of validated genes.

Project code: 110745921483. Supported by Colciencias Grant # RC No. 462-2008 awarded to Niradiz Reyes.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A24.
Abstract A30: Investigation of imatinib mesylate effect on vestibular schwannoma tumor by using in vivo corneal angiogenesis model
Authors: Avsar Timucin , Yener Ulas , Akgun Emel
Published: June 2012

Objective: Vestibular schwannomas (VSs) are histologically benign, encapsulated, and slow growing tumors that arise from Schwann cells of the vestibular branch of eighth of twelve cranial nerves (Vestibulo-cochlear nerve) that is located next to porus acusticus internus. The tested hypothesis was that gleevec reduces angiogenic capacity in patients with VSs and NF-2 associated schwannomas by using corneal angiogenesis assay. This in vivo therapeutic efficacy might induce new clinical trials in the treatment of VSs and add a medical treatment option in the armamentarium.

Methods: A total of 121 patients were treated by microsurgical VS resection at the School of Medicine, Neurosurgery Department and Institute of Neurological Sciences of Marmara University, Istanbul, Turkey between 1988–2009. Randomly selected 10 (6 sporadic VS, 4 NF-2 associated VS) samples were used. Angiogenic potential of VS and NF-2 associated VSs tumors in response to imatinib were compared with the healthy subjects by using immunohistochemistry, western blot and corneal angiogenesis assay. Results: Positive and negative control tissues showed significantly higher and lower angiogenic potential (p<0.05), compared with both sporadic and NF-2 associated VS tumor groups. Imatinib activity significantly reduced angiogenic potential, in both sporadic VS and NF-2 associated VS tumor groups. PDGF-A and PDGFR-alpha as well as PDGF-B and PDGFR-beta expression in sporadic VS and NF-2 associated VS were higher than the control groups (p<0.05).

Conclusion: The results of the present study indicate that NF-2 associated VSs showed significantly higher angiogenic potential than sporadic VSs. Moreoever, both sporadic and NF-2 associated VSs had significantly higher angiogenic potential compared with normal brain tissue. We conclude that, in the treatment of VS and NF-2 tumors, imatinib is an alternative approach to surgical resection and radiosurgery.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A30.
Abstract A41: The ASK1/IKK signaling axis mediates crosstalk between inflammation and apoptosis
Authors: Puckett Mary C. , Goldman Erinn , Cockrell Lisa , Khuri Fadlo , Fu Haian
Published: June 2012

Inflammation plays a well-established role in the promotion of tumorigenesis. The inflammatory response is mediated in large part by the inhibitor of kappa b (IKK) and nuclear factor κB (NfκB) signaling pathway. This signaling pathway can promote inflammation induced-tumorigenesis and inhibit apoptosis through protection against reactive oxygen species (ROS). The action of ROS is in part controlled by the apoptosis signal regulating kinase 1 (ASK1). ASK1 activation can initiate pro-apoptotic signaling cascades through mitogen activated protein kinases (MAPKs) Jun N-terminal Kinase (JNK) and p38. Improper regulation of ASK1 has been implicated in a wide array of diseases, including cancer. NfκB promotes tumor growth through activation of pro-growth and survival genes and decreases apoptosis through impairing JNK activation. This work has identified an unexpected, direct, non-genetic method of cell death inhibition by an upstream regulator of NfκB, IKK.

We have found that IKK can phosphorylate ASK1 Ser967, which leads to the recruitment of 14–3–3 proteins, decreased ASK1 kinase activity and ASK1-mediated apoptosis. To further elucidate the relationship between ASK1 and IKK, the interaction interface was identified and the consequences on ASK1-mediated signaling were studied. IKK and ASK1 were shown to interact in cells by immunoprecipitation of both overexpressed and endogenous proteins. Furthermore, the direct interaction between these kinases was confirmed through time resolved – fluorescence resonance energy transfer (TR-FRET). The ASK1/IKK interaction interface was dissected through iterative deletional mutagenesis and protein complementation assays. ASK1 activity was assessed by measuring H2O2 induced apoptosis, neurite outgrowth of ASK1-inducible cells, and phosphorylation of ASK1 Ser967 and downstream targets under several IKK states. IKK prevented stress-induced dephosphorylation of ASK1 and inhibited ASK1 mediated apoptosis.

These data suggest the existence of an IKK/ASK1 signaling node that negatively regulates apoptosis in response to pro-survival conditions. Characterization of this interaction could lead to development of targeted agents for ASK1 and IKK related diseases.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A41.
Abstract A8: Estrogen metabolism and mammographic density in postmenopausal women
Authors: Fuhrman Barbara J. , Brinton Louise A. , Pfeiffer Ruth M. , Teter Barbara E. , Dallal Cher , Byrne Celia , Muti Paola C. , Gierach Gretchen L.
Published: June 2012

Estrogens play important roles in the pathophysiology of breast tumors and are recognized causal factors in the etiology of breast cancer. Parent estrogens (estrone and estradiol) can be hydroxylated at the 2, 4, or 16 position of the steroid ring, resulting in metabolites with different biological activity and availability. Estrogen metabolism shows great inter-individual variation, is modifiable, and may contribute to differences among women at risk of breast cancer. We conducted a cross-sectional study to investigate whether urinary estrogens and estrogen metabolites (jointly referred to as EM) are associated with mammographic density (MD), the strongest predictor of sporadic breast cancer risk among women apart from age.

Methods: Postmenopausal women without breast cancer, aged 48–82 y, and reporting no current use of exogenous hormones were recruited and interviewed at a mammography clinic in Western NY in 2005. Concentrations of 15 EM were measured in first morning urine samples from 195 participants using liquid chromatography-tandem mass spectrometry. MD (%) was measured using computer-assisted analyses of digitized films. Linear models were used to assess associations of log-transformed EM concentrations and ratios with MD while adjusting for age, body mass index (BMI, kg/m2), and history of combination menopausal hormone therapy. We assessed effect modification by these factors and by years since menopause. Results: The median age of participants was 58, and median time since menopause was 8 years; 35% of participants were obese (BMI ≥30), and 33% had previously used combination menopausal hormones. Among all participants, urinary concentrations of parent estrogens were not associated with MD while some individual 2-pathway and 4-pathway EM had significant inverse associations with MD. Associations between EM profiles and MD were modified by years since menopause (≤8 or >8 y) and by obesity. Among women with a recent menopause, MD was positively associated with parent estrogens (p=0.02), and inversely associated with 2- and 4-hydroxylation pathway EM (p=0.03 and 0.02); these associations were not observed in women with a more distant menopause (pinteraction=0.02, 0.18, 0.16, respectively). Similarly, parent estrogens were directly associated with MD (p=0.003) among women who were obese but not among thinner counterparts (pinteraction=0.08).

Conclusion: This is the first study to examine the relations between 15 EM and MD in postmenopausal women. EM profiles were most strongly associated with MD in subgroups with higher estrogen levels including obese women and those with a more recent menopause. In these groups, more extensive 2- and 4-hydroxylation of parent estrogens was associated with reduced MD. This pattern of metabolism may influence MD by facilitating clearance of estrogens from breast tissues.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A8.
Abstract A85: Paternal age at birth is associated with leukocyte telomere length in the Nurses' Health Study
Authors: Prescott Jennifer , Han Jiali , De Vivo Immaculata
Published: June 2012

Despite the high heritability of telomere length, genome-wide association studies have not found common genetic variants with a strong influence on telomere length. A few studies have demonstrated significant correlations between the telomere length of offspring and maternal and/or paternal telomere lengths. Positive correlations have also been observed for parental age at birth and offspring telomere length, particularly with paternal age. We decided to investigate the relationship between parental age and female offspring telomere length in one of the largest studies to date, by using existing leukocyte telomere length (LTL) data that were measured by a high-throughput quantitative PCR assay for multiple prospective nested case-control studies of various cancers and cardiovascular disease in the Nurses' Health Study (NHS). We derived probit scores for each nested case-control study to standardize for between-batch variability before pooling data. Participants included in this analysis were free of cancer and other major diseases at blood draw and were restricted to the 6,647 NHS participants who reported the years their mother and father were born on the 1976 baseline questionnaire. We calculated Spearman correlation coefficients and also used generalized linear regression to calculate least-square (LS) means of LTL probit score by maternal and paternal age at birth categories. LS means were adjusted for the participant's age at blood draw. Analyses of maternal age at birth categories were additionally adjusted for continuous paternal age at birth and vice versa. The mean age of participants at blood draw was 59 years. Mean maternal and paternal age at birth were 28 and 32 years, respectively. Maternal age and paternal age at birth were highly correlated (rS=0.77, P<0.0001). After controlling for participant's age at blood draw and maternal age at birth, paternal age at birth was positively associated with the participant's LTL at blood draw (P-trend=0.003). The adjusted LS mean LTL (probit score) across paternal age categories (15–24, 25–29, 30–34, 35–39, 40–44, and 45+ years) were −0.10, −0.01, 0.01, 0.02, 0.08, and 0.19, respectively. Among the NHS participants, a one year increase in paternal age at birth corresponded to an LT L difference observed for ∼6 months of younger age. Maternal age at birth was not associated with the participant's LTL at blood draw (P-trend=0.26). In our study population, we provide evidence of an association between older paternal age at birth and longer telomere length among female offspring, but not for maternal age at birth. These results are consistent with prior literature and support the existence of temporally-regulated paternal factors in the inheritance of leukocyte telomere length among their female offspring.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A85.
Abstract A87: The association between polymorphisms in hormone metabolism and growth factor genes and mammographic density in Norwegian postmenopausal women
Authors: Ellingjord-Dale Merete , Lee Eunjung , Ozhand Ali , Couto Elisabeth , Qureshi Samera , Hofvind Solveig , Akslen Lars , Ursin Giske
Published: June 2012

Mammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD, and is known to increase breast cancer risk possibly through increased proliferation of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between mammographic density and 340 SNPs (singular nucleotide polymorphisms) from about 30 putative genes in hormone metabolism / growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004.

We assessed mammographic density on 2040 postmenopausal women aged 50–69 years using a computer assisted method (Madena, University of Southern California). We ran multiple regressions models (dominant and additive), adjusting for age, body mass index (BMI) with and without adjustments for multiple comparisons (the number of SNPs per gene). We stratified the postmenopausal women into current, past and never EPT users. For postmenopausal current EPT users there was an association between a variant in the prolactin gene (rs10946545) and MD (dominant model p=0.0002). This association was also present in women who were currently using norethisterone acetate (NETA) based EPT, a regimen common in Nordic countries. In past EPT users, we found that two variants in the catechol-O-methyltransferase gene (COMT; rs2239395 and rs5992500) were associated with MD (dominant model p=0.0112), but the association was no longer significant when we adjusted for multiple tests. Among current estrogen only users, there was an association between a variant in the cytochrome P450 gene (CYP1B1; rs4670813) and MD in current estrogen only users (dominant model p=0.0028). We also found an association between a variant in the vascular endothelial growth factor gene (VEGF; rs833052) and MD for current users of high dose NETA EPT (dominant model p=0.0021), while in low dose NETA EPT users a variant in the tumor necrosis factor gene (TNF; rs4947324) was associated with MD (dominant model p=0.0007).

We found some evidence that variants in the prolactin and COMT genes were associated with MD in current or past EPT users. We also found associations between genetic variants in TNF and MD in low dose NETA users, and between variants in VEGF and MD in high dose NETA users.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A87.
Abstract A97: Risk of biochemical recurrence after radical prostatectomy among men using 5α-reductase inhibitors and alpha-blockers
Authors: Murtola Teemu J. , Tammela Teuvo L.J.
Published: June 2012

Background: Previous studies have demonstrated that 5α-reductase inhibitors (5-ARIs) finasteride and dutasteride decrease overall prostate cancer risk, while the proportion of high risk tumors may be increased. We compared risk of biochemical recurrence and mortality after radical prostatectomy between users of 5-ARIs, alpha-blockers and medication non-users

Materials and Methods: A total of men 1,315 men who underwent radical prostatectomy at the Tampere University Hospital during 1995–2009 were included in the study cohort. Post-operatively, men were followed at six month intervals during the first postoperative year and yearly afterwards. Serum PSA was measured at each visit. Biochemical relapse was defined as PSA becoming detectable after the operation. Information on causes of death was obtained from the Finnish Cancer Registry. Data on medication purchases during 1995–2009 was obtained from national prescription database. Cox proportional regression was used to analyze hazard ratios (HRs) and 95% confidence intervals (95% CI) of biochemical relapse and death.

Results: A total of 117 men had used finasteride or dutasteride, while 372 had used tamsulosin or alfuzosin. During the follow-up 424 men had a biochemical relapse, while 124 died, of which 22 due to prostate cancer. The median follow-up time until biochemical relapse was 3.17 years and until death 5.08 years. Pathological T-stage and tumor Gleason score among users of either drug group did not significantly vary from non-users. However, 5-ARI and alpha-blocker users had more often local lymph node metastases and positive surgical margins. Prediagnostic PSA, Gleason grade, pathological T-stage and marginal positivity were all independent predictors of biochemical recurrence. Risk of biochemical relapse was comparable to non-users among 5–ARI users (HR 1.38; 95% CI 0.86–2.19), but elevated among alpha-blocker users (HR 1.71; 95% CI 1.31–2.25). However, this risk increase was only observed when alpha-blockers were being used after the surgery. Overall mortality and prostate cancer-specific mortality did not differ by medication usage.

Conclusions: Use of finasteride or dutasteride was not associated with prostate cancer grade in this population, although the users had more often local lymph node metastases and positive surgical margins. Nevertheless, the risk of biochemical recurrence and prostate cancer mortality were not affected by 5-ARI use. Our finding of increased risk of biochemical recurrence among alpha-blocker users likely reflects treatment of symptoms of aggressive prostate cancer with alpha-blockers.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A97.
Abstract A98: The association between coronary artery calcification and colorectal adenomas
Authors: Yang Moon Hee , Cho Juhee , Choi Yoon Ho , Son Hee Jung , Rhee Jong Chul , Sung Jidong
Published: June 2012

Background: Colorectal neoplasm and coronary artery disease share several risk factors. Chronic inflammation has been considered to be associated with the pathogenesis of both conditions.

Aims: To determine the association between coronary artery calcification and occurrence of colorectal adenoma.

Methods: We retrospectively evaluated 3,184 subjects who underwent colonoscopy and coronary artery calcium CT on the same day, or within a 3-month interval, during routine check-ups conducted between January 2006 and June 2009 at the Center for Health Promotion of the Samsung Medical Center.

Results: Colorectal adenomas were detected in 1,083 of the 3,184 subjects (34.0%), including 545 (39.9%) individuals with and 538 (29.6%) without coronary calcification (p < 0.01). Multiple logistic regression analysis showed that the presence of coronary artery calcification (odds ratio [OR] 1.29; 95% confidence interval [CI] 1.08–1.54), age >50 years (OR, 1.54; 95% CI, 1.28–1.86), waist circumference of 90–99 cm (OR, 1.36; 95% CI, 1.10–1.84), and current smoking status (OR, 1.29; 95% CI, 1.07–1.56), were all independent risk factors for development of colorectal adenoma.

Conclusions: Coronary artery calcium, a marker of coronary artery atherosclerosis, is significantly associated with colorectal adenoma. Further study is needed to establish a common mechanism in development of coronary artery disease and colorectal adenoma. And it may be worthwhile to evaluate the possible role of coronary atherosclerosis as an indicator of future development of colorectal carcinoma.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A98.
Abstract A99: Novel method to aid clinicians and users in choosing smartphone applications for cancer prevention and management
Authors: Passarella Ralph , McKittrick Melissa , Miller Tyler , Anderson Cheryl
Published: June 2012

Introduction: As the number of mobile healthcare applications expand, the task of choosing the best one becomes increasingly difficult for users and clinicians. To streamline this process, we developed a novel mobile app characterization tool that allows users and clinicians to make better-informed decisions. We use cancer as an example to demonstrate the effectiveness of our classification system.

Methods: Mobile apps were identified by two key methods. First, we searched Apple's App Store and the Android Market for eight key terms. From these hits we included apps that were: (a) cancer-focused, (b) publicly available (c) targeted consumers (d) had a user rating of at least ⅗ and (e) focused on disease prevention, disease diagnosis or disease management. Second, each app was characterized according to 20 relevant features. Non-binomial variables (e.g. cost of the app) were recorded when appropriate. Results: Out of over 1200 mobile cancer apps evaluated, 25 met our inclusion criteria. Of these, only five focused on disease management and only one contained personalized user feedback. The highest scoring application overall, Cancer.net Mobile, only contained 14 of 20 relevant features. Also notably, nine of 25 cancer apps focused exclusively on breast cancer while only one focused on prostate cancer.

Discussion: Thus, our system represents: (1) the first systematic approach to characterizing smartphone mobile apps related to chronic disease, (2) the first clinician and user reference tool to choosing the appropriate cancer app (3) the first systematic approach to identifying areas in need of app development. We aim to apply this system to other chronic diseases, generating a comprehensive guide for clinical decision making for mobile applications.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A99.
Abstract B100: Index-based dietary patterns and risk of breast cancer in postmenopausal women in the NIH-AARP Diet and Health Study
Authors: Wu Jennifer W. , Reedy Jill , Park Yikyung
Published: June 2012

Background: Because foods and nutrients could have synergistic or antagonistic effects when they are consumed in combination, dietary patterns in relation to diseases are a growing interest. Index-based dietary patterns that are created based on recommended dietary guidelines and Mediterranean Diet Score have been related to lower risk of some diseases. Objectives: We examined Healthy Eating Index 2005 (HEI), Alternative Healthy Eating Index (AHEI), and Alternative Mediterranean Diet Score (AMED) were associated with breast cancer risk. We also investigated the association by hormone receptor status of breast cancer.

Methods: The NIH-AARP Diet and Health Study consisted of 184,932 postmenopausal women aged 50–71 years at baseline and followed them from 1995 to 2006. The scores for each dietary pattern was calculated based on intakes assessed by a 124-items food frequency questionnaire. Cancer cases were ascertained through state cancer registries. Thirty nine percent of breast cancer cases had information on hormone receptor status. Cox Proportional hazard model, with person-years as the underlying time metric, was used to estimate the relative risk (RR) and 95% confidence intervals (CI), adjusting for potential breast cancer risk factors.

Results: During an average nine year follow up, 7,182 incident invasive breast cancer cases were identified. Both HEI and AHEI were inversely associated with risk of breast cancer. Compared with the lowest quintile of HEI, RR for the highest quintile was 0.91 (95% CI: 0.84–0.98 p-trend=0.01). RR for the highest quintile of AHEI vs. the lowest was 0.92 (95% CI: 0.85–1.00, p-trend=0.04). The AMED was also related to lower risk of breast cancer. Compared with women with low AMED score (0–3), women with high AMED score (7–9) had 10% lowered risk of breast cancer (RR: 0.90, 95% CI: 0.82–0.99, p-trend=0.01). Although it was not statistically significant, the association of index-based dietary patterns with risk of ER− was slightly stronger than those with ER+. RR for the highest quintile of HEI vs. the lowest was 0.70 (95% CI: 0.52–0.95, p-trend=0.12, n=459 cases) for ER− breast cancer and 0.95 (95% CI: 0.83–1.09, p-trend=0.30, n=2,322 cases) for ER+ breast cancer. In contrast, the highest AMED score vs. the lowest was 0.87 (95% CI: 0.73–1.03, p-trend=0.16) for ER+ and 0.91 (95% CI: 0.62–1.31, p-trend=0.26) for ER− cases.

Conclusion: Dietary patterns based on Dietary Guidelines for Americans or Mediterranean diet were related to a lower risk of breast cancer in postmenopausal women.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B100.
Abstract B108: Reexamination of total fluid intake and the risk of bladder cancer in the Health Professionals Follow-Up Study cohort
Authors: Zhou Jiachen , Smith Scott , Giovannucci Edward , Michaud Dominique
Published: June 2012

It has been hypothesized that high fluid intake may reduce contact time between carcinogens and bladder epithelial and consequently reduce carcinogenesis. Epidemiologic studies examining fluid intake and bladder cancer have been extremely inconsistent, ranging from strong inverse to strong positive associations. We reevaluated the association between fluid intake and bladder cancer among 47,909 participants in the prospective Health Professionals Follow-up Study over a period of 23 years. 823 incident bladder cancer cases were diagnosed during follow-up (1986–2008). Information on fluid intake was collected using the food-frequency questionnaire at the baseline and every four years thereafter. Cox proportional hazard regression analysis was used to adjust for risk factors for bladder cancer. Total fluid intake was inversely associated with bladder cancer when the analysis was based on the baseline diet (RR: 0.76, 95% CI: 0.60–0.97, comparing the highest total daily fluid intake quintile (>2531 ml per day) to the lowest quintile (<1290 ml per day, p-trend = 0.01). However, no association was detected when the analysis was based on recent diet or cumulative updated diet. The updated analysis for total fluid intake and bladder cancer was attenuated compared to the original findings from the first 10-year follow-up period.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B108.
Abstract B11: Routine use of a screening questionnaire improves detection of individuals that may be at risk of hereditary cancer
Authors: Koeneman Margot , Kruse Arnold-Jan , Gomez-Garcia Encarna , Gubbels Cynthia , Sep Simone , Slangen Brigitte , van Beekhuizen Heleen , Van Gorp Toon , Kruitwagen Roy
Published: June 2012

Background: Approximately 10% of all cancers are caused by a strong genetic predisposition. Identifying those individuals at genetic risk for cancer is important for proper care for prevention. Guidelines exist for appropriate referral of individuals to Cancer Genetic Services (CGS), based on family and personal medical history criteria. However, only a minority of individuals at risk for cancer predisposition are recognized either by the patients' health care providers or the patients themselves. This may be due to a suboptimal family and personal medical history taken by their health care providers. Purpose: To evaluate whether the routine use of a screening questionnaire about personal and family medical history improves the detection of individuals that may be at risk of hereditary cancer of the breasts, ovaries and/or uterus.

Methods: This pilot study was performed at the gynaecology outpatient clinic. The usual care (or common practice) referral rate to CGS, based on unstandardized anamnesis of family and personal medical history, was determined retrospectively between May 1, 2009 and April 30, 2010. Prospectively, the health care providers were asked to complete a questionnaire based hereditary cancer-risk screening tool for each new patient between June 1, 2011, and July 15, 2011. This screening tool was based on national and international guidelines, and provided a first global risk assessment of cancer predisposition. Individuals estimated to have an increased risk, were scheduled for a telephone consultation, in which a more detailed family and personal medical history was obtained to assess hereditary risk, and indication for CGS referral. Differences in proportions between groups were tested by the chi-square test.

Results: In the usual care arm, 8 of the 8630 patients (0,09%) who attended the gynaecology outpatient clinic had been referred to CGS. In the prospective arm, 500 screening questionnaires were handed out of which 203 (41%) were completed by the same health care providers. Results showed that fourteen of the patients (6.9%) who fulfilled criteria for referral, already had previous genetic counselling. Twenty-four additional telephone consultations (11.8%) were conducted, from which in five patients (2.5%) CGS referral was indicated. Referral rates differed significantly (p<0.001) between the usual care (without screening questionnaires) and prospective (with screening questionnaires) arms.

Conclusion: The routine use of a screening questionnaire improves significantly the detection and referral rate to CGS, based on consensus criteria, of individuals that may be at risk of hereditary cancer of the breast, ovaries, and/or uterus, and may benefit from professional genetic counselling and testing.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B11.
Abstract B110: Polymorphisms in xenobiotic metabolizing genes, intakes of heterocyclic amines and red meat, and postmenopausal breast cancer
Authors: Lee Hae-Jeung , Wu Kana , Cox David G. , Hunter David , Hankinson Susan E. , Willett Walter C. , Sinha Rashmi , Cho Eunyoung
Published: June 2012

Background: Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are cooked at high temperature and for long duration. Evidence from animal studies has pointed towards a possible role of HCAs in breast carcinogenesis. However, findings from previous studies on HCAs and breast cancer are inconsistent, possibly due to genetic variations in the enzymes metabolizing HCAs.

Methods: To evaluate whether the associations of intakes of estimated HCAs, meat-derived mutagenicity (MDM), and red meat with risk of postmenopausal breast cancer were modified by N-acetyltransferase 2 (NAT 2) acetylator genotype or cytochrome P450 1A2 −164 A/C (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases and 981 controls within a prospective cohort, the Nurses' Health Study (NHS). HCAs and MDM intakes were derived using a cooking method questionnaire administered in 1996.

Results: NAT2 acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM, and red meat were not associated with risk of postmenopausal breast cancer. There was also no interaction between NAT2 acetylator genotype and HCAs and MDM and red meat intake in relation to breast cancer. There was no interaction between the CYP1A2 genotype and HCAs and MDM and red meat intake in relation to breast cancer.

Conclusion: These results do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes involved in the metabolism of HCAs may modify the associations between intakes of red meat or meat-related mutagens and risk of breast cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B110.
Abstract B33: Cancer survivors as messengers
Authors: Eisinger François , Viguier Jérôme , Pivot Xavier , Blay Jean-Yves , Coscas Yvan , Roussel Claire , Morère Jean-François
Published: June 2012

Using data from the iterative EDIFICE surveys carried out in France on cancer screening behaviours in the general population, survivors were asked whether they had or not urged their relatives or friends to undergo cancer screening tests. Among our representative sample of 1564 individuals, aged 40–74 years old, 110 were cancer survivors (7%). Among the survivors, 76 (69%) declared having made positive advices for cancer screening. Interestingly 6% (7 survivors out of 110) declared that following their intervention, a cancer was found in friends or relatives after a screening test. Since there are currently 2 000 000 survivors living in France, one could consider that more than 84 000 cancers have been discovered after survivors had urged friends and/or relatives to undergo a cancer screening.

For colorectal cancer, attendance rate for screening is only about 40% of the targeted population. For a screening test like FOBT, the tumour detection rate is close to 1.25% of tested individuals. If 50% of current survivors could convince one reluctant person to undergo a screening test, every other year, then 12 500 colorectal tumours could be detected at an early stage.

Stories and personal communication are by far more effective than mass media campaign in risk management communication. For survivors who wish to be involved in cancer control, it could be hypothesized that their efficiency and impact could even be increased using inexpensive process and tools such as, communication aids such as flyers (facts and data) and/or training. The increasing number of survivors and their strong commitment could be used to convey preventive counselling and advices on cancer screening, particularly for colorectal cancer which is still underperformed.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B33.
Abstract B37: Ethnic differences in smoking rate, nicotine dependence, and cessation-related variables among adult smokers in Hawaii
Authors: Herzog Thaddeus A. , Pokhrel Pallav , Kawamoto Crissy T.
Published: June 2012

Introduction: This study tests hypotheses concerning ethnic disparities in daily cigarette smoking rate, nicotine dependence, cessation motivation, and knowledge and past use of cessation methods (e.g., counseling) and products (e.g., nicotine patch) in a multi-ethnic sample of smokers in Hawaii. Previous research has revealed significant differences in smoking prevalence among Native Hawaiians, Filipinos, Japanese, and Caucasians in Hawaii. However, no study has examined differences in dependence and cessation-related knowledge and practices among smokers representing these ethnic groups.

Methods: Participants were recruited through newspaper advertisement as part of a larger smoking cessation intervention study. Participants (N=919; M age=45.6, SD=12.7; 48% female) eligible to participate provided self-report data through mail and telephone. Subjects included 271 self-identified Native Hawaiians, 63 Filipinos, 316 Caucasians, 145 “Asians” (e.g., Japanese, Chinese), and 124 “Other” (e.g., Hispanic, African-American).

Results: Pair-wise comparisons of means, controlling for age, gender, income, education, and marital status, indicated that Native Hawaiian smokers reported statistically significantly higher daily smoking rates and higher levels of nicotine dependence compared to Asians. Native Hawaiian smokers reported significantly lower motivation to quit smoking as compared to Caucasians. Further, Filipino, and Native Hawaiian smokers reported lesser knowledge of cessation methods and products, and less frequent use of these methods and products compared to Caucasians.

Conclusions: The results suggest that Native Hawaiian and Filipino smokers could be under-served with regard to receiving cessation-related advice, and may lack adequate access to smoking cessation products and services. In addition, cessation interventions tailored for Native Hawaiian smokers could benefit from a motivational enhancement component.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B37.
Abstract B48: Inhibition of recurrence of craniopharyngiomas with imatinib mesylate-loaded poly(lactide-co-glycolide) (PLGA) microspheres
Authors: Avsar Timucin , Akgun Emel , Yılmaz Oksan Karal , Küküt Manolya , Baysal Kemal , Bayir Yasar , Seker Askın , Kilic Turker
Published: June 2012

Background: Recurrence is highly seen in craniopharyngiomas. Due to their close proximity to the vital structures, gross-total resection, which is thought to be the major determinant of the recurrence, is not always possible for craniopharyngiomas. So, post-operative long-term effective therapy approaches are needed to prevent the recurrence. Besides, our recent studies showed that there is a positive correlation between the recurrence and angiogenic potential of craniopharyngioma through over activation of PDGF (platelet-derived growth factor) signaling pathway.

Objective: In this study, we aimed to investigate the inhibitory potential of local, long-term delivery of imatinib mesylate (PDGFR-B blocker) on recurrence of adult craniopharyngiomas via PLGA-type biodegradable microspheres.

Methods: Imatinib mesylate containing PLGA polymers composed of different lactic/glycolic acid concentrations, molecular weights and drug compositions were synthesized by modified double emulsion/solvent evaporation technique. After in vitro characterization of protein holding, surface morphology, entrapment efficiency and drug release kinetics, inhibitory potential of microspheres on neovascularization was tested on craniopharyngioma tumor samples implanted in rat cornea.

Results: Imatinib containing PLGA microspheres in different LA:GA ratios (LA:GA, 50:50 (M38); 75:25(M70); 85:15(M71)) considerably reduced the neovascularization induced by recurrent tumor samples in an in vivo rat cornea angiogenesis model, p<0,01.

Conclusion: Long-term, local delivery of imatinib mesylate to the post-surgical tumoral cavity using biodegradable microspheres is promising approach to prevent the recurrence of craniopharyngiomas.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B48.
Abstract B5: Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study
Authors: Stolzenberg-Solomon Rachael Z. , Schairer Catherine , Hollenbeck Albert , Silverman Debra T.
Published: June 2012

Background: Adiposity at older age is positively associated with pancreatic cancer in many studies; however its association at younger ages and weight gain across a lifetime has not been examined extensively particular in cohort studies.

Methods: We prospectively analyzed the association between body mass index (BMI) at different ages (18, 35, 50, and > 50 years), BMI gain, and first age of overweight or obesity and exocrine pancreatic cancer in the NIH-AARP Diet and Health Study, a large cohort of men and women aged 50–71 who completed questionnaires at baseline (1995–1996) and six months later that ascertained height and weight history. During follow-up though 2006, 2120 and 1204 pancreatic cancer cases were identified in the baseline cohort among participants > 50 years (n=501,702) and sub-cohort who completed the second questionnaire (n=273,977), respectively. Hazards Ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazards with adjustment for smoking, sex, energy and total fat. Statistical tests were two sided.

Results: Compared to normal weight, overweight (body mass index, BMI >25.0–30 kg/m2) or obesity (BMI > 30 kg/m2) at ages 18, 35, 50 or > 50 years was significantly associated with elevated pancreatic cancer risk with HR ranging from 1.18 to 1.25. Adiposity gain (per 5 kg/m2) from early adulthood to older age was significantly associated with pancreatic cancer especially among never smokers (HR=1.12, 95% CI 1.04–1.21). The etiologic fraction of pancreatic cancer explained by overweight or obesity at any age in our population was 13% overall.

Conclusion: Overweight or obesity at any age is associated with a greater pancreatic cancer risk. Prevention of weight gain might prevent pancreatic cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B5.
Abstract B55: Dietary cadmium intake and risk of invasive breast cancer in the VITAL cohort
Authors: Adams Scott V. , Newcomb Polly A. , White Emily
Published: June 2012

Background: Evidence from two retrospective case-control studies suggests that cadmium is associated with risk of breast cancer. The primary routes of cadmium exposure in the general population are smoking cigarettes and eating certain foods including vegetables, grains, and seafood. To our knowledge, no reports from prospective epidemiological studies of cadmium and breast cancer risk have been published.

Methods: Dietary cadmium consumption was estimated for peri- or post-menopausal women in the VITamins And Lifestyle (VITAL) cohort by combining baseline food frequency questionnaire (FFQ) responses and US Food and Drug Administration Total Diet Study market basket survey data on the cadmium content of foods. Women reporting a personal history of breast cancer prior to enrollment in the study were excluded. The outcome of incident, invasive breast cancer was ascertained through linkage to the western Washington State Surveillance, Epidemiology, and End Results cancer registry. Women were censored at the earliest of diagnosis of in situ breast cancer, moving out of the catchment area, death, or withdrawal from the study. Multivariable adjusted Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for invasive breast cancer with increasing estimated dietary cadmium intake, adjusted for cigarette smoking history, total energy intake, total servings of vegetables and potatoes, and established breast cancer risk factors.

Results: During an average of 6 years of follow-up, 794 invasive breast cancers were registered among 31,630 women included in analysis. No evidence of an association between dietary cadmium and invasive breast cancer risk was observed in the entire analytical cohort (aHR (95% CI) comparing highest to lowest quartile dietary cadmium: 0.94 (0.63–1.38) P-trend=0.4). Similar results were obtained in analysis restricted to never-users of hormone therapy, or never-smokers. Because cadmium may compete for binding sites with zinc, we examined the interaction between dietary cadmium and estimated total intake of zinc from diet, supplements, and multivitamins; no evidence of effect modification was observed.

Conclusions: This study does not provide evidence in support of the hypothesis that dietary cadmium intake is a risk factor for breast cancer. However, non-differential measurement error in the estimate of cadmium intake was a limitation of the study that could have obscured an association.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B55.
Abstract B61: Postpartum mammary gland involution drives DCIS progression through collagen and COX-2, identifying a target for intervention
Authors: Lyons Traci R. , O'Brien Jenean , Conklin Matthew , Keely Patricia , Borges Virginia , Schedin Pepper
Published: June 2012

Prognosis of young women's breast cancer is influenced by reproductive history. Women diagnosed within five years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. We propose that breast involution following pregnancy accounts for the poor prognosis of breast cancers diagnosed postpartum. Our ‘involution hypothesis’ states that the physiologically normal microenvironment of the postpartum involuting gland is tumor promotional; however, testing the involution hypothesis has been limited by lack of pre-clinical models. We developed a mouse xenograft model of PABC that isolates postpartum mammary gland involution as a driving force for breast cancer progression and metastasis. In this model, human breast cancer cells are injected into actively involuting mouse mammary glands and nulliparous controls. Results from this model indicate that tumor cells exposed to the collagen rich involuting mammary microenvironment form larger tumors characterized by abundant fibrillar collagen, high COX-2 expression, and an invasive phenotype. In culture, these tumor cells are invasive in a collagen/COX-2-dependent manner. Importantly, in the involuting mammary gland, inhibition of COX-2 with celecoxib or ibuprofen reduced the collagen fibrillogenesis associated with involution, as well as tumor growth and lung infiltration. These anti-tumor effects were observed without blocking apoptosis of secretory mammary epithelial cells, which is required to remodel the gland to a non-secretory state, and is a requisite for advancing this strategy to clinical trial. The question of whether an NSAID based intervention study could be aimed at recently pregnant women at high risk for breast cancer remains to be determined, but is an extremely desirable objective given that there are more than 6 million pregnancies in the US per year. In summary, these data support further research to determine whether women at high-risk for postpartum breast cancer would benefit from treatment with NSAIDs during postpartum involution.

This work was funded by DOD, Komen, and ACS.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B61.