bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A31: Effects of Pin1 inhibition on tumorigenicity of glioblastoma multiforme
Authors: Avsar Timucin , Atabay Kutay Deniz , Mehmet Yıldız Taha , Kilic Turker , Karabay Arzu Korkmaz
Published: June 2012

Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor, accounting for 20% of all intracranial tumors. Current approaches in pursuit of treatment of GBM are not efficient in terms of increasing patient survivability or preventing recurrence after traditional treatments. Hunt for key molecules that might turn into drug targets have been rigorously continuing for GBM as well as other various types of tumors. Pin1, which was shown to be broadly overexpressed in various types of tumors, bears the potential to be one of the key molecular players in tumorigenesis. Molecular mechanisms underlying development and growth of the GBM, which is not completely curable by the means of chemotherapy, radiotherapy, and surgery, are not yet clearly identified. For the fact that the rate of treatment success of the agents in use against GBM is lower than acceptations, investigations for potential inhibitory target molecules for GBM development are increasing. Pin1 (peptidyl-prolyl cis/trans isomerase) is one of the molecules, recently identified and trying to be clarified during the search for potential target molecules on tumorigenicity. When compared with the health cells level of the Pin1 protein in many tumor cells like prostate, lung, breast and brain tumors is found to be extremely high. Recent studies aiming to identify Pin1's role on tumorigenicity have shown that increase in level of Pin1 in cells also led in increase of VEGF (Vascular Endothelial Growth Factor) as well. Our study aims to reveal the possible role for Pin1 as a therapeutic target and also inhibit the angiogenesis mechanism, which is common for tumors to develop, through inhibition of Pin1

U87 MG Glioblastoma cell line was used and Pin1 inhibition was performed via juglone, a Pin1 specific inhibitor molecule, and Pin1 siRNAs. Effects on Pin1 inhibition on tumorigenicity was assessed by MTT proliferation assay, wound healing assay to observe the migration characteristics, confocal microscopy technique to define morphological changes and apoptosis, and western blotting to define if angiogenesis related proteins are expressed.

It is observed that Pin1 inhibition has affected and diminished the migration ability of U87 MG Glioblastoma cells. Changes on cell morphology and activation of apoptosis were also observed with reduced expression levels of angiogenesis related genes. We believe that, this study has a potential to reveal the effects of Pin1 inhibition as a therapeutic approach and will contribute to literature and clinical care in the future.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A31.
Abstract A33: Modulation of gene expression by a cooked novel resistant starch in the colon of AOM-treated Fisher 344 rats
Authors: Zhao Yinsheng , Hasjim Jovin , Ai Yongfeng , Jane Jay-lin , Birt Diane F.
Published: June 2012

We previously reported that a cooked novel steric acid complexed high amylose starch (SAC) diet fed to Azoxymethane (AOM)-treated Fisher 344 rats significantly reduced the preneoplastic lesions, Aberrant Crypt Foci (ACF) and Mucin Depleted Foci (MDF), in comparison with water-boiled normal cornstarch (CS) diet or high amylose cornstarch (HA) diet. To determine the effect of water-boiled SAC diet on the global gene expression patterns we performed Affymetrix Genechip microarray analysis on rat colon mucosa after the rats were treated with AOM and then fed 3 different diets for 8 weeks. Genes that were significantly differentially regulated by AOM or by diet were identified. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was followed as a subsequent examination confirmed the reliability of this analysis. Microarray and qRT-PCR data showed that AOM affected gene expression for 389 genes when considering q<0.1 for AOM effect, i.e., 307 up-regulated and 82 down-regulated genes when comparing AOM-treated water-boiled CS diet group with the same diet group without AOM treatment. Further, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that most of these differentially expressed genes were associated with several important biological function such as Wnt signaling pathway, TGF-beta signaling pathway, cell cycle, and Chemokine signaling pathways. A genome-wide microarray analysis was also performed to identify the gene expression modulation by water-boiled SAC diet in AOM-treated rats comparing with AOM-treated water-boiled CS diet rats. In this analysis 408 genes were observed as differentially expressed when q<0.01, i.e., 208 up-regulated and 200 down-regulated genes, included in the signaling pathways such as DNA replication, cell cycle, RNA degradation, Steroid biosynthesis, Graft-versus-host disease, Allograft rejection, and Autoimmune thyroid disease pathways. The reliability of the microarray data was further validated by qRT-PCR. These results showed differential regulation of gene expression profiles in Fisher 344 rats fed water-boiled SAC diet compared with normal starch diet. Gene expression modification was also confirmed in the rats treated with AOM. These results provided promising targets for the suppress colonic preneoplastic lesions by SAC starch.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A33.
Abstract A37: Peripheral blood DNA methylation profiles are predictive of head and neck squamous cell carcinoma
Authors: Langevin Scott M. , Koestler Devin C. , Christensen Brock C. , Wiencke John K. , Nelson Heather H. , Houseman E Andres , Marsit Carmen J. , Kelsey Karl T.
Published: June 2012

Head and neck cancer accounts for an estimated 47,560 new cases and 11,480 deaths annually in the United States, the majority of which are squamous cell carcinomas (HNSCC). The overall 5-year survival is approximately 60% and declines with increasing stage at diagnosis, indicating a need for non-invasive tests that facilitate the detection of early disease. DNA methylation is a stable epigenetic modification that is amenable to measurement and readily available in peripheral blood. DNA methylation profiles are commonly altered in tumor tissue, including HNSCC. We applied a semi-supervised recursively partitioned mixture model (SS-RPMM) approach to identify novel blood DNA methylation markers of HNSCC using genome-wide methylation array data (26,486 autosomal CpG loci) for peripheral blood samples from 92 HNSCC cases and 92 cancer-free controls. Subjects were randomly split into training (n = 92) and testing (n = 92) sets, stratified by case-control status to ensure an equal distribution of cases and controls between sets. A series of mixed effects models were fit to the training data only and CpG loci were ranked according to absolute t-statistic. The top M loci were selected to train a classifier, where M was chosen using a nested cross-validation procedure, which was then fit to the testing data. To assess the performance of the resultant markers in the testing data, we constructed receiver operating characteristic (ROC) curves and calculated the corresponding area under the curve (AUC). Cases and controls were best differentiated by a methylation profile of 6 CpG loci (associated with FGD4, SERPINF1, WDR39, IL27, HYAL2 and PLEKHA6), resulting in 4 classes, with an AUC of 0.73 (95% CI: 0.62–0.82). After adjustment for subject age, gender, smoking, alcohol consumption and HPV16 serostatus, the AUC increased to 0.85 (95% CI: 0.76–0.92). There was no significant difference in stage at diagnosis, tumor site or HPV-16 serostatus for cases by class. We have identified a novel blood-based methylation profile that is predictive of HNSCC with a high degree of accuracy. Although not yet adequate for use in clinical settings, this profile demonstrates the potential of DNA methylation measured in blood for development of non-invasive applications for detection of head and neck cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A37.
Abstract A43: PPARδ promotes colonic inflammation and inflammation-associated tumorigenesis
Authors: Wang Dingzhi , Guo Lixia , Ning Wei , DuBois Raymond N.
Published: June 2012

Although epidemiologic and experimental evidence strongly indicates chronic inflammation as a risk factor for cancer, it remains unclear how chronic inflammation contributes carcinogenesis. Here we show that deletion of PPARδ diminishes colonic inflammation by reducing infiltration of immune cells via downregulation of pro-inflammatory chemokines and cytokine in a mouse model of colon inflammation. These chemokines are responsible for recruitment of leukocytes from the circulation to local inflammatory sites. Our results further reveal that COX-2 is a downstream target of PPARδ and COX-2-derived PGE2 stimulates macrophages to produce pro-inflammatory chemokines and cytokine. PGE2 is a crucial mediator of colorectal carcinogenesis. More importantly, loss of PPARδ attenuated colonic inflammation-associated adenoma growth in two mouse models of inflammation-associated colorectal cancer. Our results demonstrate that PPARδ promotes chronic colonic inflammation and colitis-associated tumorigenesis. Collectively, these findings indicate that PPARδ plays a pivotal role in connecting colonic inflammation to cancer progression and may represent a potential therapeutic target for prevention or treatment of colorectal cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A43.
Abstract A45: Targeting breast cancer stem cells using cancer preventive rexinoids
Authors: Zhao Jing , Zhang Yun , Hill Jamal L. , Mazumdar Abhijit , Brown Powel H.
Published: June 2012

Background: Recent research in breast biology supports the cancer stem cell hypothesis which asserts that malignancies arise in tissue stem cells through dysregulation of self-renewal. The cancer stem cell hypothesis has important implications for early detection, prevention and treatment of breast cancer. If breast cancers arise from the transformation of normal stem cells, it may be possible to target stem cells for the prevention of cancer. We have previously shown that rexinoids prevent the development of ER-negative breast cancer in transgenic mouse models. Previous studies have demonstrated a role of retinoid signaling in the regulation of normal breast stem cell self-renewal and differentiation. Bexarotene and LG100268 are rexinoids that selectively bind RXR receptors. Based on the effects of these molecularly targeted agents, we hypothesize that rexinoids prevent breast cancer development by suppressing the growth and transformation of the breast stem cell population.

Methods: We performed in vivo and in vitro studies to address our hypothesis. Cell proliferation assays were used to determine whether rexinoids can inhibit the growth of normal, pre-malignant and malignant breast cell lines (HMECs, MCF10A, DCIS.COM, SUM225, HCC1937 and HCC38 cell lines). To determine whether these agents affect stem cells, we performed mammosphere assays and FACS analysis after treatment with vehicle or rexiniods. We next conducted in vivo studies using MMTV-Wnt transgenic mice treated with LG100268 (50mg/kg) or vehicle, and studied the stem cell properties of mammary epithelial cells from these mice. The stem cell population in mammary glands was quantified by staining of CD24, CD49f and using FACS analysis and mammosphere assays.

Results: Our results showed that the rexionids LG100268 and bexarotene inhibit the growth of breast cell lines only at a high concentrations (the IC50 (concentration that reaches a 50% growth inhibiton) in most of the tested cell lines exceeded 10uM). Results of in vitro mammosphere assays showed that 100nM LG100268 reduced mammosphere formation efficiency by more than 40% in all breast cancer cell lines. Results from our in vivo experiments showed that LG100268 reduced the mammary epithelial stem cell population by 57% as defined by the CD24+/CD49f++ population identified by FACS and by 47% as measured by in vitro mammosphere assays.

Conclusion: These results from in vitro and in vivo studies demonstrate that the rexinoid LG100268 is a potent mammary stem cell inhibitor. This study shows that rexinoids suppress stem cell expansion and suggest that mammary stem cell inhibitors will be useful breast cancer preventive agents. This work is supported by a grant from the Breast Cancer Research Foundation (to PHB) and from an NIH/NCI RO1 grant (CA078480) (to PHB).

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A45.
Abstract A61: Prognostic relevance of genome-wide association studies-identified single nucleotide polymorphisms in primary breast cancer
Authors: Bayraktar Soley , Thompson Patricia A. , Yoo Suk Young , Do Kim-anh , Sahin Aysegul A. , Arun Banu , Bondy Melissa L. , Brewster Abenaa M.
Published: June 2012

Purpose: Several single nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS).

Methods: A cohort of 739 white women with early-stage breast carcinoma was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648, rs3803662, rs12443621, rs8051542, rs999737, rs6504950, rs4973768), using Illumina GoldenGate platform. The relationships between SNPs and breast cancer outcomes were evaluated using univariate and multivariate Cox proportional hazard regression models. The cumulative effects of SNPs were assessed by computing the number of at-risk-alleles based on the results from the univariate analyses. In addition, we explored higher-order interactions between clinical variables and SNPs using classification and regression tree (CART) analysis.

Results: Four SNPs (rs2981582, rs1219648, rs12443621 and rs6504950) were significantly associated with OS using univariate Cox proportional hazard regression analysis (P≤0.1) and there was no association with DFS. In multivariate model adjusted for age, hormonal status, clinical stage, and treatment, rs12443621 (16q12) and rs6504950 (17q23) polymorphisms remained as independent prognostic markers for OS. Compared with the GG/AG reference group, homozygous carriers of minor A allele for rs12443621 and rs6504950 had an increased risk for death (HR:1.38, 95% CI:1.01 to 1.86; P=0.04, and HR:1.80, 95% CI:1.18 to 2.77; P=0.007, respectively). In multivariate analysis, a higher risk for death was found in the sub-cohort of patients harboring 3–4 at-risk-alleles of the GWAS SNPs compared to patients carrying ≤2 at-risk-alleles (HR:1.5, 95% CI:1.14 to 1.85; P=0.002). In CART modeling, women with stage 2 breast cancer who did not receive chemotherapy and were carries of the AA genotype for rs6504950 had the highest risk for death (HR:10.0, 95% CI:3.47 to 28.78).

Conclusion: SNPs in previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), were also found to be independent prognostic markers for OS in breast cancer patients. The precise molecular mechanisms through which these SNPs influence clinical outcomes remain to be determined.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A61.
Abstract A66: Apoptosis, cell cycle, DNA repair, immune, and metabolism pathway SNPs modify bladder cancer risk, recurrence, and survival
Authors: Andrew Angeline S. , Gui Jiang , Moore Jason H. , Karagas Margaret R. , Pendleton Eben , Schned Alan R. , Mason Rebecca A. , Wyszynski Asaf , Tanyos Sam A. , Kelsey Karl T. , Marsit Carmen J. , Zens Michael S.
Published: June 2012

Bladder cancer is the fourth most common malignancy in U.S. men. Current treatments for non-invasive bladder tumors often appear initially effective, yet the rates of recurrent disease are high. Clinically useful predictors of the recurrent bladder cancer phenotype have not yet been identified. Major biological processes involved in bladder carcinogenesis include apoptosis, cell cycle, DNA repair, immune surveillance, and xenobiotic metabolism. We hypothesized that genetic variation in genes involved in each of these pathways may modify bladder cancer susceptibility and prognosis. Methods: To examine the independent and interacting effects, we analyzed variant genotypes hypothesized to modify these processes in 818 transitional cell carcinoma cases and 1167 controls enrolled in a case – control study of incident bladder cancer conducted in New Hampshire, U.S.A. Cases were followed over time to ascertain recurrence and survival status. We evaluated gene–gene interactions using Multifactor Dimensionality Reduction (MDR). Results: In the metabolism pathway, the variant form of the metabolism gene HSD3B2 was associated with increased risk (adjusted OR 1.85 95%CI 1.31–2.62) and ALDH2 variants had shorter time to first bladder cancer recurrence (adjusted HR non-invasive 1.94 95%CI 1.32–2.84). We observed longer survival among bladder cancer cases with non-invasive tumors associated with DNA repair XRCC4 heterozygous genotype compared with wildtype (adjusted HR 0.53 95%CI 0.38–0.74) and for invasive cases for immune pathway GATA3 heterozygotes (adjusted HR 0.11 95%CI 0.03–0.39). Conclusions: Our analysis suggests candidate SNPs for further clinical evaluation as prognostic markers and may lead to more personalized bladder cancer surveillance guidelines.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A66.
Abstract A68: Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and lobule type in the Nurses' Health Study II
Authors: Rice Megan S. , Tamimi Rulla M. , Connolly James L. , Collins Laura C. , Shen Dejun , Pollak Michael N. , Rosner Bernard , Hankinson Susan E. , Tworoger Shelley S.
Published: June 2012

Introduction: Previous research in the Nurses' Health Study (NHS) and NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans.

Methods: We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999. A pathologist, blinded to exposure status, classified lobule type in normal adjacent tissue on available biopsy slides according to the number of acini per lobule. For each participant, the pathologist determined the predominant lobule type (i.e., type 1, 2, or 3) and whether any type 1 or any type 3 lobules were present. Lobule type then was classified as: 1) predominant type 1/no type 3 lobules, which is suggestive of complete involution or 2) other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, IGF binding protein-3 (IGFBP-3), and the ratio of IGF-1-to-IGFBP-3 levels with lobule type.

Results: In univariate analyses, greater age, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type1/no type 3 lobules (p<0.05). In multivariate models adjusting for age and assay batch, higher IGF-1 levels were associated with decreased odds of predominant type 1/no type 3 lobules (OR quartile 4 vs. quartile 1=0.37, 95%CI: 0.15–0.89). Greater ratios of IGF-1-to-IGFBP-3 levels also were associated with decreased odds of predominant type1/no type 3 lobules (OR quartile 4 vs. quartile 1=0.26, 95%CI: 0.11–0.64). These results were slightly attenuated after adjustment for other potential predictors of lobule type.

Conclusion: Higher IGF-1 levels and a greater IGF-1-to-IGFBP-3 ratio were associated with decreased odds of having predominant type 1 lobules/no type 3 lobules among women with proliferative BBD in the NHSII. This study provides further evidence for the role of growth factors in the structure of breast lobules and lobular involution.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A68.
Abstract A75: Calorie restriction and rapamycin, but not exercise, inhibit mammary tumor growth in a mouse model of postmenopausal obesity
Authors: Nogueira Leticia , Dunlap Sarah M. , Ford Nikki A. , Hursting Stephen D.
Published: June 2012

Obesity is a well-established risk factor for postmenopausal breast cancer and is associated with poor outcomes in both premenopausal and postmenopausal women. Given that approximately one third of the US population is obese, interventions to reverse the detrimental effects of obesity on breast cancer progression are urgently needed. The molecular target of Rapamycin (mTOR) modulates pathways regulating energy balance and cell growth. Therefore, agents that target the mTOR pathway are promising for breaking the obesity-breast cancer link. Here, we directly compared the two most recommended strategies for reversing obesity, calorie restriction (CR) and exercise (EX), and a well-established mTOR inhibitor (rapamycin) on mammary tumor growth and metabolic profiles in obese mice.

Ovariectomized C57BL/6 mice were administered a diet-induced obesity regimen for 8 weeks, then randomized into 3 diet or exercise treatment groups: Control (AIN-76A diet fed ad libitum to maintain the obese state, n=30); 30% CR (70% of the carbohydrate calories but otherwise isonutrient relative to control, n=15); EX (control diet fed ad libitum plus treadmill exercise regimen, n=15). Mice were orthotopically implanted (4th mammary gland) with syngeneic MMTV-Wnt-1 mammary tumor cells at week 12. Of the 30 mice in the control group, 15 received rapamycin (5mg/kg, administered ip every 48hrs) starting at week 14. All other mice received vehicle treatment (saline, administered ip every 48 hrs) starting at week 14. Tumors were excised at week 18. Final tumor weights from mice in the CR (0.043 ± 0.007 g) and rapamycin (0.072 ± 0.010 g) groups, but not EX (0.380 ± 0.072 g) group, were significantly reduced compared to control (0.390 ± 0.066 g).

The crucial role of mTOR in the link between obesity and breast cancer progression was confirmed in a follow up study where constitutive activation of mTOR (mTOR) ablated the inhibitory effects of CR on mammary tumor growth. CR failed to reduce tumor weight in mice injected with cells transfected with mTOR (0.38 ± 0.05 g), compared to control (0.55 ± 0.08 g). Transfection effect bias was discarded since CR significantly reduced weight of tumors (0.29 ± 0.03 g) in mice injected with cells transfected with WT mTOR, compared to control (0.62 ± 0.12 g).

We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity-breast cancer progression link.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A75.
Abstract A82: Can telomere length be modified in healthy people?
Authors: Washechek-Aletto Jill R. , Engelman Corinne , Thibodeau Stephen N. , Petersen Gloria M. , Cunningham Julie M. , Boardman Lisa A. , Opyrchal Seung M. , Devine Megan M. , Viker Kimberly B. , Johnson Ruth A. , Skinner Halcyon G. , Seo Songwon , Gangnon Ronald , Litzelman Kristin
Published: June 2012

Short constitutional telomere length has been associated with aging and cancer, but how telomere length is affected by other epidemiologic or environmental variables in health has not been thoroughly studied. Understanding these associations with telomere length in health is important for studies to evaluate the relationship of telomere length and diseases such as cancer. We measured peripheral blood leukocyte DNA telomere length with quantitative PCR in 1977 non-related healthy controls collected through the Colon Cancer Family Registry (an NCI cooperative group) and through the Mayo Biobank and Biobank for Gastrointestinal Health Research, two IRB approved prospective biospecimen collections based at Mayo Clinic, Rochester, MN. The controls were a median age of 50.6 years old, and 49.6% of the controls were male. Ninety-six percent of the controls were white; 1.8% were Asian, and <1% were either black, Pacific Islander, or Native American. Less than 1% of controls were Hispanic. On univariate analysis, as age increased, telomere length decreased (Pearson correlation coefficient = −0.07, 95% CI: −0.11, −0.03). Telomeres were longer in people who consumed more fruits (p<0.01) and vegetables (p<0.01); took aspirin on a regular basis (p<0.01); or had a family history of cancers of any type (p=0.05). Women had longer telomeres than men (p=0.03). Telomeres were shorter in people who consumed alcohol (p<0.01), took folate on a regular basis (p=0.01), or who consumed red meat (p<0.01). Statistical significance was not found in the following variables: tobacco use, diagnosis of diabetes, intake of calcium, use of hormone replacement therapy in women, or body mass index. On multivariate analysis, age, vegetable consumption, family history of colorectal cancer or any type of cancer, and folate intake were identified as being significantly associated with telomere length. Telomere length may be associated with multiple environmental and demographic variables in healthy individuals, and adjusting for these may be important for studies that test for an association between telomere length and diseases such as cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A82.
Abstract A9: Phenotype matters in the prediction of cancer risk of oral premalignant lesions (OPL)
Authors: Zhang Lewei , Guillaud Martial , Poh Catherine , MacAulay Calum , Rosin Miriam
Published: June 2012

Histology remains the most reliable way for predicting cancer risk of premalignant (preinvasive) lesions if the OPLs show high-grade changes (i.e. severe dysplasia or carcinoma in situ, CIS): however, it is a poor predictor of the cancer risk of OPLs with no or low-grade (mild/moderate) dysplasia (termed LGOPL). It is possible that there are subtle histological differences between progressing LGOPLs and nonprogressing LGOPLs. In a recent retrospective study (Cancer Research 2008, 68:3099–107), we have shown that nuclear phenotypic score (NPS) as measured by a computer-driven microscope imaging system could serve as an adjunct tool to assist pathologists in judging the progression risk of LGOPLs Objective: to assess the potential of this new tool in identifying high-risk LGOPLs from an ongoing prospective study and to give an interim report of our results.

Methods: 284 primary LGOPLs from 284 patients were studied: 47 hyperplasias, 116 mild and 121 moderate dysplasias. Thoinin-Feulgen stained sections were imaged and analyzed to generate a NPS for each sample. The NPS was correlated with histopathology, clinical variables and outcome (progression to severe dysplasia, CIS or invasive cancer).

Results: Elevated NPS was significantly associated with progression: high NPS (≥ 4.5) was associated with a 4.7-fold increase in risk of progression as compared to low NPS (< 4.5). Of the 199 LGOPLs with low NPS, 13 (7%) progressed as compared to 26/85 (31%) of LGOPLs with high NPS (P < 0.0001). In the multivariate Cox model, high NPS was a significant risk predictor for cancer progression (P < 0.0001).

Conclusions: These data support the potential utility of automated quantitative microscopy technology to assist the pathologist in assessing progressing potential of low-grade OPLs (Supported by grant R01DE13124, NIDCR).

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A9.
Abstract B1: Deciding between ethic standards for cancer screening
Authors: Eisinger Francois
Published: June 2012

The underfunding of upstream interventions (prevention and screening) is often seen as a mistake, for the least. However, whatever your moral theory might be, reallocation in favor of very early detection is questionable. From a deontological perspective and according to the rule of rescue described by Al Jonsen in its contribution “Bentham in the Box” a society should look first at helping the threatened ones (the affected ones) whether it is cost-effective or not. Spending “more” money for treatment would therefore be the result of a self-imposed moral duty. In contrast screening and even more prevention, appear to be, in this perspective less mandatory. However for utilitarian advocates, looking for the “best” allocation is looking for the most cost-effective one and prevention, screening and care be assessed/compared without that kind of moral bias.

In this perspective, it is useful to make a clear distinction between early diagnosis and screening. According to the quantitative relationship between stages and survival, more than the 2/3 of what could be gained lay in a shift from stage II to stage I, and not a in a shift from stage I to an earlier state. This latter attempt would be costly with few returns (the standard neoclassical production function with decreasing returns). Therefore, allowing every stage II case to be diagnosed at stage I, will yield more benefits and more equity (distributive justice). Even more, if we can be confident in expecting that almost every tumor of 2 cm will grow and spread, in contrast the natural history of a very small tumor will be more heterogeneous. Which screened small prostate cancers will be threatening (or not) is a key question. I believe that new biological markers will give us that critical information, and for that matter, that biological paradigm of cancer (the kind of the tumor) will overcome the anatomical paradigm (the size of the tumor).

Lastly, even if the pace of discovery for screening tools might be fast and full of promises, to understand the growing interest in screening programs it would be useful to have also a sociological perspective considering the rise of a surveillance medicine (M. Foucault and D. Armstrong).

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B1.
Abstract B10: Factors predicting decisional conflict and p53 genetic testing intention among those at risk of Li-Fraumeni syndrome
Authors: Hovick Shelly R. , Pentz Rebecca , Jackson Michelle A. , Bojadzieva Jasmina , Strong Louise C. , Peterson Susan K.
Published: June 2012

Background: Li-Fraumeni syndrome (LFS) is a rare genetic condition that increases lifetime risk for a variety of cancers in children and adults. LFS is due to an inherited mutation in the p53 tumor suppressor gene. While genetic testing may help LFS families better understand their cancer risks, decisions to undergo testing may be difficult given the psychosocial implications of testing and the lack of clarity about screening and surveillance methods that are most appropriate for LFS-related cancers. Previous research has shown decisional conflict, or one's perceived difficulty in making decisions about genetic testing, to be a strong predictor of p53 testing intention. However, little is known generally or specifically among LFS-affected families about the factors that predict decisional conflict. We tested a theoretical model of factors (Hall, Manne, Winkel et al., 2011) that contribute to decisional conflict, including genetic testing self-efficacy, genetics knowledge and testing pros and cons. Additionally, we expanded upon the model by assessing the contribution of risk perceptions and worry and the extent to which the model also predicts p53 genetic testing intentions.

Methods: Participants (N=139) in this study were from 27 LFS-affected families enrolled in a longitudinal study offering p53 genetic counseling and testing, including those affected (N=29) and unaffected (N=110) by cancer.

Results: Analysis using generalized estimating equations shows higher testing self-efficacy is associated with lower levels of decisional conflict (B=0.09, p<.01). Worry is also shown to moderate the effect of risk perception on decisional conflict (B=0.04, p<.01) whereby higher risk perceptions predict lower decisional conflict when worry is also high. Lower decisional conflict in turn, is associated with higher p53 genetic testing intention (B=1.04, p<.01). Those with more knowledge about genetics also had lower intentions to test (B=-0.10, p<.01).

Conclusions: These findings support previous research showing decisional conflict to be an important predictor of genetic testing intention among those at-risk of LFS and suggest decisional conflict may help further explain how psychological factors (e.g. perceived risk, self-efficacy, worry) impact genetic testing intention. Thus, these findings offer support for the development of decision aids for p53 genetic testing and suggest these aids should communicate risk and build self-efficacy in order to reduce uncertainty surrounding testing decisions. Additionally, results suggest that those with strong cognitive and emotional responses to risk will have more confidence in their decisions whether to test.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B10.
Abstract B102: Serum compounds involved in the one-carbon metabolism and urothelial cell carcinoma risk: A nested case-control study within EPIC
Authors: Ros Martine M. , Bueno-de-Mesquita H Bas , Aben Katja KH , Kampman Ellen , Buchner Frederike L. , Jansen Eugene H.J.M. , Kiemeney Lambertus A.
Published: June 2012

Introduction: Folate is, in combination with vitamin B6, vitamin B12 and homocysteine, involved in one-carbon-metabolism affecting DNA synthesis and methylation which may play a role in carcinogenesis. This nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) is the first prospective study that investigated associations between prediagnostic serum folate, homocysteine, vitamin B6 and vitamin B12 and the risk of urothelial cell carcinomas (UCC).

Methods: 847 UCC first incident cases were matched to 847 controls for gender, age at baseline, study center, date of blood collection, time of day of blood collection, and fasting status. Serum concentrations of folate and vitamin B12 were determined with an immuno-analyser. Serum vitamin B6 concentrations were measured by reverse-phase high-performance liquid chromatography (HPLC) and serum homocysteine concentrations by an enzyme cycling assay. Incidence rate ratios (IRR) were estimated with conditional logistic regression with detailed adjustment for smoking status, smoking duration and smoking intensity. All analyses were conducted for total UCC and for two prognostic subgroups of UCC, defined by tumor stage and grade. Ta grade 1 or 2 tumors were defined as non-aggressive (n=377) while all other grade and stage combinations were defined as aggressive (n=395).

Results: A reduced risk of UCC was found for higher levels of serum folate (IRR highest vs. lowest quartile 0.73; 95%CI 0.52–1.01, p-trend=0.04), although this was apparent only for current smokers. Serum folate was inversely associated with aggressive UCC risk (IRR highest vs. lowest quartile 0.59; 95%CI 0.37–0.95, p-trend=0.04), but not with the risk of non-aggressive UCC. No associations were observed between serum homocysteine, vitamin B6 and B12 and UCC risk.

Conclusion: This large European cohort study shows that high serum concentrations of folate may reduce the risk of UCC, in particular the risk of aggressive UCC. However, residual confounding by smoking can not be excluded.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B102.
Abstract B106: Coffee consumption and the risk of skin cancer
Authors: Song Fengju , Qureshi Abrar , Han Jiali
Published: June 2012

Objective: An association between caffeine intake and the risk of skin cancer has been suggested in animal studies, but has not been well established in epidemiologic studies. The objective of this study is to prospectively examine the association between coffee consumption and the risk of skin cancer.

Materials and Methods: Using data from two large cohorts in the U.S., the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we prospectively examined the risks of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma according to coffee consumption. In the NHS, 72,921 participants were followed up from June 1984 to June 2008. In the HPFS, 39,976 participants were followed up from June 1986 to June 2008. We documented 25,480 incident skin cancer cases in the two cohorts, which comprised 22,786 BCC, 1,953 SCC, and 741 melanoma cases. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and skin cancer risk factors.

Results: A significantly inverse association was found between coffee consumption and BCC risk. The dose-response relationship was significant (P trend < 0.0001 in women, and P trend = 0.005 in men). Compared with people who consumed coffee < 1 cup/month, those who consumed > 3 cups/day had a RR of 0.80 (95% CI: 0.75, 0.85) in women, and 0.91 (95% CI: 0.81, 1.02) in men. The amount of caffeine consumption was also inversely associated with BCC risk. The highest quintile had the lowest risk (in women RR = 0.82; 95% CI: 0.78, 0.87, and in men RR = 0.87; 95% CI: 0.81, 0.94, both P trend < 0.0001). Decaffeinated coffee consumption was not associated with a decreased risk of BCC. Neither SCC nor melanoma was found to be inversely associated with coffee consumption.

Conclusion: Coffee consumption is inversely associated with BCC risk in women and men, likely through the effect of caffeine. Further studies are warranted to investigate the underlying mechanism.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B106.
Abstract B115: A pooled analysis of smoking and alcohol drinking and risk of multiple myeloma in the International Multiple Myeloma Consortium
Authors: Andreotti Gabriella , Benhaim-Luzon Veronique , Brennan Paul , de Sanjose Silvia , Caudet Laura Costas , Costantini Adele Seniori , Cocco Perluigi , Becker Nikolaus , Foretova Lenka , Maynadie Mark , Nieters Alexandra , Birmann Brenda , Staines Anthony , Miliken Kevin , Weisenburger Dennis , Baris Dalsu , Baris Dalsu , Purdue Mark , DeRoos Anneclaire , Spinelli John , Cozen Wendy , Camp Nicola , Moysich Kirsten , Chiu Brain , Boffetta Paolo
Published: June 2012

Risk of multiple myeloma (MM), a highly fatal cancer, is increased in older age, men, African Americans, and persons with monoclonal gammopathy of undetermined significance (MGUS). Modifiable risk factors for MM remain obscure. Tobacco and alcohol use findings are inconsistent. To further assess the etiologic role of these lifestyle factors, the International Multiple Myeloma Consortium (IMMC) pooled individual-level questionnaire data from 6 case-control studies with alcohol data (n: cases=1,484, controls=6,542) and 9 case-control studies with smoking data (n: cases=2,662, controls=11,890). A pooled multivariable logistic regression analysis using a random effects model and adjusting for age, race, and study center location showed a decreased MM risk among men who reported ever drinking alcohol regularly compared with non-drinkers [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.57–0.87], while results among women were null (OR 0.98, 0.76–1.26). Frequency, duration, and cumulative lifetime consumption of alcohol use were not linearly associated with MM risk among men or women. Neither a history of cigarette smoking compared to never smokers, nor any quantification of dose or duration of smoking was associated with MM risk in the pooled study population. Our findings are very similar to those reported from a pooled analysis of smoking and alcohol use conducted among case-control studies of non-Hodgkin lymphoma, a collection of lymphoid malignancies that are predominatly B-cell in origin, like MM (1, 2). Prospective studies may provide further insight into the association between alcoholic beverage consumption and MM risk.

References:

1. Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS, Stagnaro E, Willett EV, Dal Maso L, Serraino D, Chang ET, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Hartge P; InterLymph Consortium. Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. Lancet Oncol 2005;6:469–76.

2. Morton LM, Hartge P, Holford TR, Holly EA, Chiu BC, Vineis P, Stagnaro E, Willett EV, Franceschi S, La Vecchia C, Hughes AM, Cozen W, Davis S, Severson RK, Bernstein L, Mayne ST, Dee FR, Cerhan JR, Zheng T. Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). Cancer Epidemiol Biomarkers Prev 2005;14:925–33.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B115.
Abstract B24: Common and persistent adverse outcomes following prostate cancer treatment: Findings from the Michigan Prostate Cancer Survivor Study
Authors: Yassine May Darwish , Copeland Glenn , Wei John T. , Demers Raymond Y.
Published: June 2012

Context: Advances in screening and treatment of prostate cancer have dramatically increased the number of survivors in the U.S. population. Previous studies have typically only reported outcomes of treatment and symptoms within a short time following treatment, leaving a need for a study of long-term, post-treatment symptoms experienced by survivors because the persistence of such symptoms over time necessitates an improvement of survivor care.

Objective: To perform a population based survey of prostate cancer survivors in the Michigan Cancer Registry to identify treatment side effect rates and assess areas of need in survivors' care.

Design, Setting, and Patients: Linking case files of the Michigan Cancer Registry with records from the National Death Index, we identified prostate cancer patients diagnosed between 1985 and 2004 and alive on December 31, 2005. Participants were selected using a stratified cross-sectional sampling strategy to ensure adequate inclusion of survivors based upon race and ethnicity, urban versus rural location, and number of years since diagnosis of prostate cancer. A total of 2,499 surveys were completed and returned.

Main Outcome Measures: Rates of bowel, sexual, urinary, and vitality symptoms by treatment (prostatectomy monotherapy, external beam radiation monotherapy); level of problem posed by symptom as rated by patient.

Results: Median duration between prostate cancer diagnosis and survey response was 9 years. 80% of study population was diagnosed at early stage. Patient-reported outcomes of “moderate” to “big” problems in the four weeks prior to survey completion: sexual symptoms, 51.6%; vitality, 24.1%; urinary, 19.7%; bowel, 14%.

Conclusion: Persistent symptoms subsequent to prostate cancer treatment suggest a gap in symptom management. Future research should support long-term studies of active surveillance vs. active treatment outcomes to understand the feasibility of minimizing the burden of long-term physical symptoms arising from prostate cancer treatment.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B24.
Abstract B25: Cancer survival by stage among Koreans
Authors: Shim Young Mog , Shin Myung-Hee
Published: June 2012

Background: Five-year relative survival rates (5y-RSRs) calculated from the Korean National Cancer Registry (KNCR) data have been reported recently, but the stage distribution among the registered patients is still unknown. We aim to calculate stage-specific 5y-RSRs using a large cancer registry data from one hospital that has contributed 7.1% of the KNCR data between 1999 and 2008.

Method: Samsung Medical Center Cancer Registry System has been established since 1994. We identified all cancer patients diagnosed between Nov. 1, 1994 and Dec. 31, 2006 and followed them up through Dec. 31, 2008. We calculated 5y-RSRs using Ederer II expected survival rates. Stage-specific 5y-RSRs were calculated for those cancers that had stage information for more than 50% of the patients.

Results: A total of 82,038 cancer records were analyzed. Five-year-RSR had improved with time periods. Five-year-RSR for all cancer was 52.6 % in 1994–1999 and 60.3 % in 2000–2004. During 1999–2006, the highest 5y-RSR was obtained from thyroid, breast and prostate cancers and the lowest from pancreas, gallbladder, and lung cancers. Five-year-RSR for stage I, II, III, and IV cancers were 0.95, 0.80, 0.58, and 0.18, respectively. Site specific 5y-RSR of stomach, liver and lung cancer was 0.99, 0.65, and 0.79, respectively, in stage I, and 0.09, 0.07, and 0.04, respectively, in stage IV.

Conclusions: Stage-specific 5y-RSRs among Koreans were comparable to other developed countries, and fairly good for common cancers in Korea such as stomach, liver, and lung cancers.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B25.
Abstract B29: Screening and communication with physicians for women with Lynch syndrome: Findings from a qualitative study
Authors: Burton Allison M. , Sun Charlotte C. , Daniels Molly S. , Boyd-Rogers Stephanie , Lynch Patrick M. , Lu Karen H. , Peterson Susan K.
Published: June 2012

Background: Lynch syndrome, which is also known as hereditary non-polyposis colon cancer (HNPCC), is an autosomal dominant hereditary cancer syndrome that confers women with a 40–60% lifetime risk of endometrial cancer (EC) and a 12% lifetime risk of ovarian cancer (OC). Consensus statements recommend annual EC and OC screening for women with Lynch syndrome, initiated at age 30–35 or 10 years younger than the earliest known case in the family. This study evaluated the prevalence of EC and OC screening behaviors among women at risk for Lynch syndrome, and communication with their physicians about EC and OC risk and screening needs.

Methods: Women age > 25 years who were at risk for Lynch syndrome-related cancers, and who had not had both a hysterectomy and oophorectomy, completed a semi-structured interview either in person or over the phone. The domains covered included demographics and medical history, knowledge of screening recommendations, screening for Lynch-syndrome associated gynecological cancers, and physician-patient communication. SPSS and NVivo™ were used for data analysis.

Results: Fifty-two women (mean=40.6 years old) participated. They were mostly white, married, well-educated, and had children. Approximately 70% were Lynch-syndrome mutation carriers while the remaining 30% met the Amsterdam II criteria. Approximately 70% reported a family history of EC or OC. All but five had received genetic counseling regarding their risk for Lynch syndrome. Half of the participants correctly answered questions about the appropriate age to begin screening, while approximately 75% correctly assessed the recommended screening frequency. Approximately half of the women reported never having had asymptomatic gynecological screening. Between 15 and 38% were currently adherent to screening recommendations because they received screening as part of a research study. Women who were seeing non-oncology gynecologists were not offered appropriate EC or OC screening, although they uniformly expressed a high level of trust and value in the care provided by these physicians and believed that their physicians were doing the best job possible to manage their health needs. Approximately 33% of the women report that cost and lack of insurance might prevent their screening adherence in the future.

Conclusions: Lynch syndrome-affected families and their primary care physicians may lack accurate knowledge of EC and OC risks. Women who are at risk for Lynch syndrome may not receive appropriate EC or OC screening from their community physicians, and new prevention-communication strategies may be needed. Participation in research studies may improve adherence to screening for gynecologic cancers in Lynch syndrome.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B29.