bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A53: Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment
Authors: Koyama Fernanda C. , Ramos Camila M. Lopes , Fernandes Jennifer M. , Ledesma Fernanda C. , Alves Venancio A F , Vailati Fernanda C. , Habr-Gama Angelita , Perez Rodrigo O. , Camargo Anamaria A.
Published: May 2019

Resistance to therapy is the major obstacle to a favorable outcome in cancer treatment. Neoadjuvant chemoradiotherapy (nCRT) can lead to complete tumor regression in a significant proportion of patients with rectal cancer (up to 40%). The possibility of avoiding radical surgery and its associated functional consequences for those who present complete response has become increasingly attractive, but approximately 60% of patients have only partial or no tumor remission after nCRT. In order to identify molecular mechanisms determining poor response to nCRT and to uncover optimized treatment strategies, we have conducted global gene expression analysis followed by pathway enrichment analysis in pretreatment biopsies from patients showing complete or poor clinical response to nCRT. We show that mitochondrial oxidative phosphorylation and phosphatidylinositol signaling pathways are consistently altered in rectal tumors comparatively. Both pathways have already been associated with resistance to radiation and chemotherapy in solid tumors and appear to converge on the activation of the Akt pathway in nonresponding tumors. To further address the role of Akt activation in response to nCRT, we evaluated by immunohistochemistry, Akt activation in an independent set of pretreatment biopsies from rectal cancer patients and observed not only high pAkt levels in those presenting poor response to nCRT but also that nuclear pAkt can also discriminate resistant tumors. We also evaluated the combination of an allosteric Akt-inhibitor MK2206 to chemoradiation in a radioresistant colorectal cancer cell line SW480 either in vitro and in vivo and observed an improvement of 50% of tumoricidal effect. Altogether, our results indicate that activation of the Akt pathway is a key event affecting response to nCRT and that combining chemoradiotherapy and Akt inhibitors such as MK2206 may significantly improve response rates to neoadjuvant therapy in rectal cancer.

Citation Format: Fernanda C. Koyama, Camila M. Lopes Ramos, Jennifer M. Fernandes, Fernanda C. Ledesma, Venancio A F Alves, Fernanda C. Vailati, Angelita Habr-Gama, Rodrigo O. Perez, Anamaria A. Camargo. Akt inhibitior MK2206 combination to neoadjuvant radiotherapy: Improving the rectal cancer treatment [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A53.
Abstract A61: Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy
Authors: Oliveira Ângela das Neves , Correia Lucas Ian Veloso , Arantes Lídia Maria Rebolho Batista , Carvalho Ana Carolina de , Messias Elisa Alves , Sorroche Bruna Pereira , Eguchi Flávia Coltri , Rodrigues Renata Santos , Melendez Matias Eliseo , Carvalho André Lopes
Published: May 2019

Background: Head and neck cancer is the sixth most common cancer site worldwide and is associated with low survival and high mortality rates, when diagnosed in advanced stages. The pursuit for potential therapeutic targets in natural resources may lead to the development of new antineoplastic agents. Several compounds coming from venomous animals are being tested in clinical trials due to their high selectivity and different physiologic activities. In this way, ant-venom glands are composed of bioactive molecules, such as peptides/proteins and allergens, which may be considered as potential therapeutic agents for oncology.

Objectives: The aim was to identify potential therapeutic proteins expressed in venomous glands of Ectatomma opaciventre ants, for the treatment of head and neck squamous cell carcinoma (HNSCC) tumors.

Materials and Methods: The mRNA library of Ectatomma opaciventre was sequenced using Illumina NextSeq 500 platform (76 bp unpaired-end) and NextSeq 500/550 Mid Output v2 kit (150 cycles). Libraries were constructed using TruSeq Stranded mRNA LT Sample Prep Kit (Illumina). A de novo assembly of the Ectatomma opaciventre transcriptome was performed using Velvet software.

Results: The RNA-seq of E. opaciventre venom gland generated 55,131,904 raw reads. The de novo Velvet assembly produced 23,254 contigs, which matched against 12,061 NCBI-Blastn transcripts. From these contigs, 437 full-length transcripts were identified, from which two potential therapeutic genes were selected: SPARC and Phospholipase B. Both SPARC and Phospholipase B genes have been previously described as having antitumor properties.

Conclusions: In conclusion, this deep transcriptome sequencing may have identified two potential therapeutic proteins, which are being analyzed in HNSCC cell lines.

Citation Format: Ângela das Neves Oliveira, Lucas Ian Veloso Correia, Lídia Maria Rebolho Batista Arantes, Ana Carolina de Carvalho, Elisa Alves Messias, Bruna Pereira Sorroche, Flávia Coltri Eguchi, Renata Santos Rodrigues, Matias Eliseo Melendez, André Lopes Carvalho. Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A61.
Abstract A62: In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors
Authors: Sales Natiely Silva , Diniz Mariana de Oliveira , Silva Jamile Ramos , Silva Mariângela de Oliveira , Porchia Bruna F. M. M. , Aps Luana R. M. M. , Ferreira Luis Carlos Souza
Published: May 2019

Cervical cancer associated with persistent papilloma virus infections (HPV) is a public health problem and represents the third most frequent type of cancer in women. Our group developed a DNA vaccine against HPV-induced tumors based on the expression of the HPV-16 E7 oncoprotein genetically fused to the HSV-1 glycoprotein D (gD) (pgDE7h). This vaccine is capable of promoting antitumoral effects against tumor cells expressing HPV-16 E6 and E7 proteins (TC-1 cells) and induces specific cellular immune responses. In view of the low success rate of DNA vaccines in clinical trials, in vivo electroporation (EP) is a promising strategy for plasmid delivery, leading to increased cellular transfection and enhanced immune responses. In this study, C57BL/6 mice were inoculated with TC-1 cells subcutaneously and immunized 3 days later with pgDE7h intramuscularly, associated or not with EP. Immune responses were analyzed 14 days after vaccination and tumor growth was monitored for 60 days. Similar antitumor effects were obtained with 10-fold less DNA associated with EP when compared to the group that was inoculated only with DNA, reaching around 20% of tumor-free mice. Dose-response curves indicated that maximum protective immunity was achieved with 50 ug of vaccine inoculated with EP, promoting 100% of antitumor protection. This group also had enhanced frequencies of cytotoxic lymphocytes expressing the degranulation marker CD107a and high in vivo cytotoxic activities. Besides that, a delayed vaccination performed 10 days after the TC-1 injection led to 70% of tumor-free mice until the end of the observed period. Collectively, these data confirmed that EP can be used as an efficient method of DNA vaccine delivery and should be further studied to improve the chances of cancer vaccine success in clinical trials.

Citation Format: Natiely Silva Sales, Mariana de Oliveira Diniz, Jamile Ramos Silva, Mariângela de Oliveira Silva, Bruna F. M. M. Porchia, Luana R. M. M. Aps, Luis Carlos Souza Ferreira. In vivo electroporation improves the immune responses induced by a DNA vaccine and confers complete antitumor protection against HPV-associated tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A62.
Abstract B17: Gene therapy and chemotherapy cooperate to inhibit prostate cancer progression in an animal model
Authors: Tamura Rodrigo Esaki , Strauss Bryan Eric
Published: May 2019

Patients with localized prostate carcinoma have a 5 year-survival rate of almost 100%; however, for patients with metastatic disease the rate is 31%, and mortality in 90% of these cases is the result of metastases. Clearly, there is a need for novel therapies and room for improving existing modalities. We propose that gene therapy and chemotherapy, when combined, may provide superior tumor cell killing. Our laboratory has developed a novel adenoviral vector expressing p53 under the control of a p53 responsive promoter; thus a positive feedback mechanism is established, providing high levels of p53, resulting in cell death of prostate cancer cells in vitro and in vivo. In previous assays, we have shown that our vector (AdRGDPGp53) is more effective than typical gene therapy approaches which employ a constitutive promoter (CMV) to control expression of p53. Here, we evaluate whether the union of gene therapy and chemotherapy applied to prostate cancer cell lines would promote a synergistic response in the induction of programmed cell death and reduction of tumor progression in an animal model. We combined AdRGDPGp53 along with the chemotherapy drugs used in the clinical treatment of prostate carcinoma, mitoxantrone, docetaxel, or cabazitaxel. Our results indicate that all drugs increase phosphorylation of p53, leading to improved induction of p53 targets. In vitro experiments indicate that AdRGDPGp53 sensitizes prostate cancer cells to each of the drugs tested, conferring increased levels of cell death. In a xenograft mouse model of in situ gene therapy, AdRGDPGp53 treatment, when combined with cabazitaxel, drastically reduced tumor progression and increased survival rates to 100%. Strikingly, we used a sub-therapeutic dose of cabazitaxel, thus avoiding leukopenia, yet still showed potent antitumor effects when combined with AdRGDPGp53 in this mouse model. The AdRGDPGp53 approach warrants further development for its application in gene therapy of prostate carcinoma.

Citation Format: Rodrigo Esaki Tamura, Bryan Eric Strauss. Gene therapy and chemotherapy cooperate to inhibit prostate cancer progression in an animal model [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B17.
Abstract B24: Role of Dermcidin in growth and survival of melanoma tumor cells
Authors: Montoya Jennifer N. , Perez-Sosa Marcela N. , Sangiuliano Beatriz A. , Belizario Jose E.
Published: May 2019

Dermcidin (DCD) is a candidate oncogene localized at 12q13.1 which is normally expressed in the skin sweat gland and brain and overexpressed in various tumor cells. We have established the role of DCD in melanoma growth and survival by silencing DCD via shRNA expression in human melanoma G361 cell line. Biologic and biochemical assays showed that DCD gene knockdown decreased significantly melanoma cell growth in culture and tumor formation in NUDE mice. A DNA microarray-based study identified a total of 162 upregulated and 212 downregulated genes, in a G-361 control clone (pLKO) and clones expressing shRNA to DCD mRNA (IBC-I). We found, notably, genes involved in the nucleosome organization and signaling pathway to APRIL/BAFF receptor. Additionally, we examined DCD expression by immunohistochemistry in TMA (tissue microarray) of 101 patients and found that DCD-negative tumor had a 65.54% survival rate and DCD-positive tumor 43.33% survival rate in 5 years. We found an association with BRAF V600E and ERBB4 mutation in DCD-positive tumor with most frequent E43K mutation. Finally, we have screened clones resistant to Vemurafenib after long-term treatment in vitro and in xenografts in nude mice. Overall, these studies provide further support for DCD as oncogene to melanomas.

Financial support: FAPESP, CNPq and CAPES.

Citation Format: Jennifer N. Montoya, Marcela N. Perez-Sosa, Beatriz A. Sangiuliano, Jose E. Belizario. Role of Dermcidin in growth and survival of melanoma tumor cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B24.
Abstract B48: Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line
Authors: Cassinela Edson Kuatelela , Oliveira Grabriela Pintar , Landemberger Michele Christine , Martins Vilma Regina
Published: May 2019

Background: Gastric cancer is the fourth most common cause of cancer death worldwide and one of the tumors with higher mortality rates in Brazil. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness, resulting in treatment failure. The mechanisms of gastric cancer pathogenesis are largely unknown, as is what causes limitations in the personalized treatment. Neoadjuvant therapy has been largely applied in these tumors because it can improve tumor resectability and survival of patients. However, tumors can develop resistance during chemotherapy, or this resistance can be present intrinsically before chemotherapy. Indeed, mechanisms associated to chemotherapy resistance in gastric cancer are complex and multifactorial; understanding the variety of these factors that are involved in chemoresistance is of great relevance.

Materials and Methods: Gastric adenocarcinoma cell line (AGS) was treated with increased concentration of 5-fluorouracil to generate a resistant cell (rAGS_FU). Extracellular vesicles (EVs) secreted from AGS and rAGS_FU cell lines were isolated by ultracentrifugation, quantified, and evaluated regarding their aggressiveness through invasion and colony assays. Proteomics analysis of EVs and secreting cells were performed to identify potential markers for chemotherapy resistance in gastric cancer cell lines.

Results: We found proteins involved in resistance to chemotherapy upregulated in EVs derived from resistant cells; parental cells treated with EVs derived from resistant cells were able to promote high colony formation and increased invasion potential. Thus, cells resistant to chemotherapy have a more aggressive phenotype and are able to transfer these acquired characteristics to the nonresistant ones using EVs. We compared the proteomes of EVs derived from the two cell lines and revealed important pathways that can be associated with chemoresistance in gastric cancers.

Conclusion: It is crucial to understand these chemoresistance mechanisms and develop efficient treatment strategies to overcome them. A deep investigation of these data is needed to understand and create new opportunities for the discovery of new biomarkers of response to chemotherapy in gastric cancers and contribute to the better understanding of the biologic role of molecules shuttled by EVs.

Citation Format: Edson Kuatelela Cassinela, Grabriela Pintar Oliveira, Michele Christine Landemberger, Vilma Regina Martins. Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B48.
Abstract B62: Intratumoral genetic heterogeneity in rectal cancer and response to neoadjuvant chemoradiotherapy
Authors: Masotti Cibele , Bettoni Fabiana , Correa Bruna R. , Habr-Gama Angelita , Gama-Rodrigues Joaquim , Viana Maria , Vailati Bruna B. , Juliao Guilherme P. Sao , Fernandez Laura M. , Galante Pedro A. F. , Perez Rodrigo O. , Camargo Anamaria A.
Published: May 2019

Response to neoadjuvant chemoradiotherapy (nCRT) varies substantially among patients with locally advanced rectal cancer, but key determinants of treatment response are not fully understood. Intratumoral genetic heterogeneity (ITGH) is a common feature of solid tumors and has been proposed to drive disease progression and treatment response. Others and we have recently demonstrated that primary nontreated rectal tumors exhibit significant ITGH, but the effect of nCRT in shaping the clonal architecture of rectal cancer has not yet been addressed. In the present work, we further expanded the analysis of ITGH in rectal cancer by analyzing whole-exome sequencing (WES) and clinical data from 79 primary nontreated rectal cancers obtained from The Cancer Genome Atlas. We show that primary rectal tumors exhibit a remarkable variability in the degree of ITH. We also analyzed the effect of nCRT on ITGH and monitored tumor cell subpopulation dynamics after treatment through WES of paired tumor samples collected at diagnosis (pretreatment) and at surgery following nCRT (post-treatment) from seven patients. We show that treatment exposure does not introduce novel somatic mutations or significantly alter tissue genetic heterogeneity. Instead, nCRT acts as a potent selective pressure, shaping the mutational landscape of rectal tumors and allowing the selection and expansion of tumor cell subpopulations, which are more prone to resist nCRT. Our results shed light on the highly heterogeneous and dynamic mutational landscape of rectal tumors and indicate that ITGH may directly affect response to nCRT.

Citation Format: Cibele Masotti, Fabiana Bettoni, Bruna R. Correa, Angelita Habr-Gama, Joaquim Gama-Rodrigues, Maria Viana, Bruna B. Vailati, Guilherme P. Sao Juliao, Laura M. Fernandez, Pedro A. F. Galante, Rodrigo O. Perez, Anamaria A. Camargo. Intratumoral genetic heterogeneity in rectal cancer and response to neoadjuvant chemoradiotherapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B62.
Abstract B64: The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation
Authors: Mehic Merima , Sá Vanessa Karen de , Hebestreit Sandra , Heldin Paraskevi , Heldin Carl Henrik
Published: May 2019

Introduction: Lung cancer is the result of a multistep accumulation of genetic and/or epigenetic alterations; therefore, a better understanding of the molecular mechanism by which these alterations affect lung cancer pathogenesis would provide new diagnostic procedures and prognostic factors for early detection of recurrence. The remarkable qualitative and quantitative modifications of extracellular matrix components as the deubiquitinating enzyme (USP17), hyaluronan (HA), and hyaluronan synthases 2 (HAS 2) may favor invasion, cellular motility, and proliferation in several cancers including lung.

Results: The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. Numerous epithelial cells expressed USP17 and HAS2 in dysplasia compared to squamous cell carcinoma (SqCC) (p=0.001). USP17 and HAS2 were prominently expressed in adenocarcinoma (ADC) (p≤0.005). HA immunostaining indexes were increased in ADC and SqCC compared to normal and dysplasia cells (p=0.05). Consistent with the immunohistochemical analyses, low amounts of hyaluronan and USP17 were observed in SqCC by confocal analysis, coincident with less colocalization as determined by confocal microscopy. In contrast, a high expression of hyaluronan (48% of positive index) and high USP17 expression (78% of positive index) in ADC was consistent with a higher degree of colocalization.

Conclusions: HAS2, hyaluronan and USP17 were expressed at higher levels in particular in preneoplastic lesions and ADC, suggesting a role in NSCLC oncogenic transformation, possibly by promoting cellular division by USP17-mediated. Elucidation of the mechanism of how USP17 and HAS2 cooperate in the regulation of the cell cycle might be of therapeutic importance.

Citation Format: Merima Mehic, Sr., Vanessa Karen de Sá, Sr., Sandra Hebestreit, Sr., Paraskevi Heldin, Sr., Carl Henrik Heldin, Sr.. The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B64.
Abstract B74: Prevention of breast cancer by withanolides
Authors: Singh Shivendra V.
Published: May 2019

Malignancy of the breast is a leading cause of cancer-related deaths among women globally. Feasibility of breast cancer prevention is illustrated by clinical success with SERMs and aromatase inhibitors for ER+ breast cancers. However, a clinically viable preventive intervention targeting ER-negative breast cancers is still lacking. Constituents of Ayurvedic medicine, which has been practiced in India for thousands of years, continue to draw attention for identification of novel small molecules potentially useful for prevention of chronic diseases including cancer. This presentation summarizes efficacy data, molecular targets, and biomarkers of mammary cancer prevention by a small-molecule steroidal lactone (withaferin A) derived from an Ayurvedic medicinal plant (Withania somnifera). This work was supported by the grant US PHS grant RO1 CA142694-05 from the National Cancer Institute.

Citation Format: Shivendra V. Singh. Prevention of breast cancer by withanolides [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B74.
Abstract A07: Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: A nationwide study in Sweden
Authors: Huang Jiaqi , Magnusson Måns , Törner Anna , Ye Weimin , Duberg Ann-Sofi
Published: May 2019

Background: A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association.

Methods: HCV and HBV-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIR), and with a matched reference population (1:5 matching) using Cox proportional hazards regression model to calculate Hazard Ratios (HR).

Results: In total 340,819 person-years in the HCV-cohort and 102,295 in the HBV-cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIR was 2.1 (95% CI: 1.4, 2.9) for HCV infection and the SIR 1.4 (0.5, 3.3) for HBV infection. In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders of chronic obstructive pulmonary disease, diabetes mellitus, chronic pancreatitis and diagnoses related to alcohol abuse.

Conclusion: This nationwide population-based cohort study demonstrated an increased risk of pancreatic cancer among HCV-infected individuals, although this excess risk was attenuated but still statistically significant after adjustment for other potential risk factors. Our results support the hypothesis that HCV infection might be associated with an increased risk of pancreatic cancer, but further studies, with more complete information about other potential confounding factors, are needed to verify the association and to explore the causality.

Citation Format: Jiaqi Huang, Måns Magnusson, Anna Törner, Weimin Ye, Ann-Sofi Duberg. Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: A nationwide study in Sweden. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A07.
Abstract A35: Associations between time spent sitting and cancer-related biomarkers: An exploration of effect modifiers
Authors: Jung Su Yon , Paxton Raheem J. , Hays-Grudo Jennifer , Paskett Electra , Hursting Stephen D. , Fenton Jenifer , Pollak Michael , Vitolins Mara , Chang Shine
Published: May 2019

Purpose: Despite convincing evidence that prolonged periods of sitting may influence critical biological mediators of cancer development, few studies assessed the relationship between time spent sitting and cancer-related biomarkers.

Methods: This cross-sectional study included 825 postmenopausal women who were enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. Plasma levels of biomarkers were measured at the third annual visit. The time spent sitting per day was categorized as quartiles (Qs) and analysis of covariance was used to assess the relationships between sedentary time and cancer biomarkers.

Results: No clear linear patterns were observed between the time spent sitting and levels of biomarkers; however, these relationships were modified by race, physical activity level, and exogenous estrogen use. Insulin-like growth factor-I (IGF-I) levels among black women were higher than those of white women across the Qs of time spent sitting. Likewise, IL-6 levels in black women were higher than those in white women at Q3 and Q4 of sedentary time. IGF binding protein-3 levels were higher and insulin levels were lower among women meeting guidelines for physical activity than women who were not across the Qs of sedentary time. Additionally, C-reactive protein levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time.

Conclusions: Few meaningful associations were observed between the time spent sitting and the cancer-related biomarkers. More research is needed to characterize the relationship between time spent sitting and cancer-related biomarkers in the context of pertinent effect modifiers.

Citation Format: Su Yon Jung, Raheem J. Paxton, Jennifer Hays-Grudo, Electra Paskett, Stephen D. Hursting, Jenifer Fenton, Michael Pollak, Mara Vitolins, Shine Chang. Associations between time spent sitting and cancer-related biomarkers: An exploration of effect modifiers. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A35.
Abstract A39: Gene-environment interactions between SNPs in the renin-angiotensin-aldosterone system and hypertension, obesity, and blood pressure-related dietary exposures regarding renal cell cancer risk
Authors: Deckers Ivette AG , Brandt Piet A. van den , Engeland Manon van , Godschalk Roger , Schouten Leo J.
Published: May 2019

Background: Hypertension and obesity may increase renal cell cancer (RCC) risk, but the underlying mechanism is not well understood. Given that sodium, potassium and fluid intake influence blood pressure (BP), genetic variants in the renin-angiotensin-aldosterone system (RAAS) may constitute to RCC development, as RAAS regulates BP and sodium balance.

Methods: The Netherlands Cohort Study on diet and cancer with case-cohort design includes 120,852 participants aged 55-69 years. At baseline, diet and lifestyle factors were assessed using questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the iPLEX Gold system and MassARRAY software (Sequenom, Hamburg). After 20.3 years of follow-up, 13 candidate single nucleotide polymorphisms (SNPs) in seven RAAS genes known to be involved in BP regulation or sodium balance were available for Cox proportional hazards analyses for 3,583 subcohort members and 503 cases.

Results: Two SNPs, AGTR1_rs1492078 (AA vs. GG) and AGTR1_rs5186 (CC vs. AA), were associated with RCC risk in the total population [hazard ratio (95% confidence interval): 0.70 (0.49-1.00) and 1.49 (1.08-2.05), respectively] and in participants with hypertension. AGT_rs3889728 (AA + AG vs. GG) showed a lower RCC risk in participants with hypertension and a higher RCC risk in participants without hypertension (P-interaction = 0.039). Associations between sodium intake and RCC risk differed among genotypes of RAAS SNPs, but tests for these and other SNP-environment interactions were not significant.

Conclusion: SNPs in AGTR1 and the interplay between AGT_rs889728 and hypertension may influence RCC susceptibility. SNP-environment interactions with obesity, potassium intake and fluid intake were not significant. For sodium intake we can neither conclude nor exclude that such interactions may contribute to RCC risk.

Citation Format: Ivette AG Deckers, Piet A. van den Brandt, Manon van Engeland, Roger Godschalk, Leo J. Schouten. Gene-environment interactions between SNPs in the renin-angiotensin-aldosterone system and hypertension, obesity, and blood pressure-related dietary exposures regarding renal cell cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A39.
Abstract A43: Circulating concentrations of serum 25-hydroxyvitamin D and colorectal adenoma
Authors: Choi Yoonji , Kim Young Ha , Cho Chang Ho , Kim Sung Hi , Lee Jung Eun
Published: May 2019

Introduction: Vitamin D has been suggested to decrease a risk of colorectal neoplasia. We examined the association between serum 25-hydroxyvitamin D (25(OH)D) levels and colorectal adenoma in Korea adults.

Methods: We conducted a case-control study among 364 patients (112 cases and 252 controls). Participants who underwent colonoscopy completed questionnaires and provided blood samples. Serum 25(OH)D were measured using the radioimmunoassay (RIA). We used multivariable logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal adenoma.

Results: The mean values of serum 25(OH)D among controls were 16.8 ± 5.1 ng/ml for men and 16.6 ± 6.6 ng/ml for women. With adjustment for potential confounding variables, serum levels of 25(OH)D were not significant associated with adenoma in men (ORs = 0.94, 95% CIs = 0.26-3.40 compared the highest quartile with the lowest quartile). However, women in the highest quartile of serum 25(OH)D levels had a significant lower prevalence of colorectal adenoma compared to those in the lowest quartile (OR = 0.32, 95% CIs = 0.11-0.94).

Conclusion: Our results suggest that there is an inverse association between serum 25(OH)D levels and colorectal adenoma in Korea women.

Citation Format: Yoonji Choi, Young Ha Kim, Chang Ho Cho, Sung Hi Kim, Jung Eun Lee. Circulating concentrations of serum 25-hydroxyvitamin D and colorectal adenoma. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A43.
Abstract A45: Consumption of artificially and sugar-sweetened carbonated beverages and risk of non-Hodgkin lymphoid neoplasms: The Cancer Prevention Study-II Nutrition Cohort
Authors: McCullough Marjorie L. , Teras Lauren , Shah Roma , Diver Ryan , Gaudet Mia M. , Gapstur Susan M.
Published: May 2019

Background: The sweetener aspartame received regulatory approval for use in carbonated beverages 30 years ago, but debate continues over its safety. Only two prospective studies have examined the relationship between artificially-sweetened beverages and incidence of non-Hodgkin lymphoma (NHL), with one study finding no association and the other suggesting possible increased risk.

Objective: We examined the associations of consumption of artificially- and sugar- sweetened carbonated beverages and total aspartame intake with risk of incident NHL, overall and by major histologic subtypes in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort.

Methods: Included in this analysis were 100,442 men and women, average age 69.2 (SD ± 6.1) years. Participants reported consumption of diet and regular soda in 1999 and 2003, in addition to information on medical history, lifestyle and anthropometric factors. During a 10 year follow-up, 1,196 self-reported NHL cases were verified through medical record or state cancer registry linkage. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI).

Results: Average daily consumption of diet and regular soda at baseline was less than a half serving/day. In men and women combined, we observed no association between consumption of one or more servings/day of diet (RR=0.92, 95% CI 0.73, 1.17, p trend=0.14) or regular (RR=1.10, 95 % CI 0.77, 1.58, p trend=0.62) soda and total NHL risk, compared to no consumption (p heterogeneity by sex>0.1); both models controlled for consumption of the other beverage. Aspartame intake was not associated with NHL risk (RR=1.02, 95% CI 0.84, 1.24 p trend=0.69, comparing top to bottom quintile of intake). Associations with NHL subtypes (multiple myeloma, DLBCL, CLL/SLL, follicular, other B cell lymphoma) were similarly null except for an inverse trend for consumption of artificially sweetened soda with risk of multiple myeloma (RR=0.70, 95% CI 0.42, 1.17 for 5+ servings/week vs. none, p trend=0.05).

Conclusion: In this cohort of older men and women, daily consumption of artificially- or sugar- sweetened sodas is not associated with increased risk of NHL. Further research in younger cohorts is needed to examine associations with higher amounts of consumption.

Citation Format: Marjorie L. McCullough, Lauren Teras, Roma Shah, Ryan Diver, Mia M. Gaudet, Susan M. Gapstur. Consumption of artificially and sugar-sweetened carbonated beverages and risk of non-Hodgkin lymphoid neoplasms: The Cancer Prevention Study-II Nutrition Cohort. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A45.
Abstract A52: ZIP11 and susceptibility to renal and bladder cancer
Authors: Wu Lang , Rabe Kari G. , Parker Alexander S. , Petersen Gloria M.
Published: May 2019

Introduction: Laboratory studies have demonstrated that zinc and zinc transporters play important roles in the development of urological cancers, including prostate, bladder, and renal cell cancer. To date however, there have been no efforts to evaluate whether germline variation in zinc transporter genes alter the risk of developing these cancers. Motivated by this, we evaluated associations of known variants in zinc transporter genes with risk of prostate, bladder, and renal cell cancer using three NCI Genome Wide Association Study (GWAS) data sets downloaded from dbGaP.

Methods: Data consisted of GWAS data from the PLCO Screening Trial (prostate; 1172 cases, 1157 controls); Bladder Cancer study (3527 cases, 5119 controls); and Renal Cancer study (1453 cases, 3531 controls). All genotyped variants in 10 ZNT family genes (ZNT1-ZNT10) and 14 ZIP family genes (ZIP1-ZIP14) in each data set were analyzed by logistic regression models to evaluate the association of each variant with risk of developing prostate, bladder, and renal cancer, respectively. We evaluated these associations in a univariable setting, after adjusting for available covariates, such as age and gender. Correction for multiple comparisons used Max T permutation tests.

Results: One variant in ZIP11, rs8081059, was associated with increased risk of renal cancer (OR=1.28, 95% CI= 1.13-1.45; corrected p= 0.049). Another ZIP11 variant, rs11871756, was associated with an increased risk of bladder cancer risk (OR=1.43, 95% CI 1.24-1.63; corrected p=0.0002). We also found three variants in ZIP11 associated with a decreased risk of bladder cancer: rs11077654 (OR=0.76, 95% CI 0.68-0.85; corrected p=0.001), rs9913017 (OR=0.76, 95% CI= 0.68-0.85; corrected p=0.002), and rs4969054 (OR=0.78, 95% CI 0.69-0.88; corrected p=0.02). Interestingly, these three protective variants are within the same LD block. There were no associations between zinc transporter variants and prostate cancer risk.

Conclusion: We report for the first time that specific genetic variants of a zinc transporter gene, ZIP11, are associated with risk of renal and bladder cancer. If validated in larger, more focused studies, further investigations are warranted to explore the functional significance of ZIP11 in these two cancers.

Citation Format: Lang Wu, Kari G. Rabe, Alexander S. Parker, Gloria M. Petersen. ZIP11 and susceptibility to renal and bladder cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A52.
Abstract A54: Vitamin D and risk of colorectal cancer: The Melbourne Collaborative Cohort Study
Authors: English Dallas R. , Williamson Elizabeth J. , Heath Alicia K. , Ebeling Peter R. , Baglietto Laura , Hodge Allison M. , Giles Graham G. , Kvaskoff David , Eyles Darryl
Published: May 2019

Introduction: Several nested case-control studies have found that high serum or plasma levels of 25-hydroxy vitamin D (25OHD) are associated with decreased risk of colorectal cancer. Most of these studies were conducted in areas with lower UVB irradiance than Australia. To determine whether 25OHD was associated with reduced risk of colorectal cancer in Australia, we conducted a case-cohort study nested within a cohort study.

Methods: The Melbourne Collaborative Cohort recruited 41,514 participants from 1990-94. At baseline, blood samples were collected. This study was restricted to participants with dried blood spots from baseline blood samples. We included a random sample of 2996 people (i.e. subcohort), together with all incident cases of colorectal cancer during follow-up. 25OHD was measured using liquid chromatography tandem mass-spectrometry. The data were analysed with Cox regression, using Barlow's method to allow for the case-cohort design and adjusted for sex, education, physical activity, waist circumference, country of birth (southern Europe versus other), smoking, and intakes of alcohol, energy, margarine and processed meat.

Results: The method showed high reliability; the intra-class correlation from 500 repeat measurements was 0.78 (95% CI: 0.75, 0.82). In a separate calibration study, there was good agreement between 25OHD measurements from dried blood spots and plasma and for the subcohort, the predicted mean plasma concentrations were 55.5 nmol/L for males and 46.0 for females. During an average of 14 years of follow-up, we identified 563 cases. There was a weak, non-statistically significant inverse association between 25OHD and colorectal cancer; the hazard ratio for the highest versus lowest quartile was 0.82 (95% CI: 0.61, 1.10, p trend = 0.20).

Conclusions: In this Australian study, the association between 25OHD and risk of colorectal cancer was weaker than has been observed in studies from Europe and North America.

Citation Format: Dallas R. English, Elizabeth J. Williamson, Alicia K. Heath, Peter R. Ebeling, Laura Baglietto, Allison M. Hodge, Graham G. Giles, David Kvaskoff, Darryl Eyles. Vitamin D and risk of colorectal cancer: The Melbourne Collaborative Cohort Study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A54.
Abstract A57: Alcohol consumption and plasma sex steroids in premenopausal women
Authors: Hirko Kelly A. , Hankinson Susan E. , Eliassen A. Heather
Published: May 2019

Purpose: Alcohol consumption is a consistent risk factor for breast cancer, and evidence suggests premenopausal plasma hormones are associated with breast cancer. In this study, we examined the association between alcohol consumption and plasma sex steroid hormones in premenopausal women.

Methods: We assessed the cross-sectional association between alcohol intake and circulating sex steroid concentrations among 2,034 premenopausal women in the Nurses' Health Study II (NHSII). Plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, prolactin, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulphate (DHEAS) were measured in samples collected in 1996-99. Estrogens were measured in both the follicular and luteal phases of the menstrual cycle, while androgens were measured in the luteal phase as well as in random samples that were not timed in the menstrual cycle. Average alcohol intake was calculated from semi-quantitative food frequency questionnaires collected in 1995 and 1999.

Results: Alcohol consumption was positively association with concentrations of luteal estrone (p-trend<0.0001) and luteal estradiol (p-trend=0.0001). Women who consumed more than 20 grams of alcohol per day, compared with non-drinkers, had higher concentrations of luteal estrone (geometric mean 98.0 vs. 79.9 pg/mL) and luteal estradiol (152.5 vs. 123.3 pg/mL). We did not observe statistically significant associations between alcohol and follicular estrogens, luteal estrone sulfate, testosterone, androstenedione, progesterone, prolactin, DHEA or DHEAS.

Conclusion: Alcohol consumption was significantly positively associated with luteal estrogen concentrations, but not with plasma androgen levels, nor estrogens measured in the follicular phase. Thus, luteal estrogen levels may mediate the association between alcohol and breast cancer.

Citation Format: Kelly A. Hirko, Susan E. Hankinson, A. Heather Eliassen. Alcohol consumption and plasma sex steroids in premenopausal women. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A57.
Abstract A65: Effect of voluntary running on metastasis in a mouse model of breast cancer
Authors: Rundqvist Helene , Mijwel Sara , Ahlstedt Emil , Lindholm Carolin , Strell Carina , Roswall Pernilla , Pietras Kristian , Johnson Randall , Ostman Arne
Published: May 2019

Introduction: Breast cancer is one of the most common neoplastic diseases. Emerging evidence states that regular physical exercise provides a risk reduction for breast cancer by approximately 25 %. In addition, recent studies suggest that physical activity may also have an effect on recurrence and mortality. Mouse models are suitable tools to study anti-neoplastic mechanisms.

Aim: To evaluate the effect of voluntary running on tumor initiation, growth and metastasis in mouse models of breast cancer.

Methods: From 4 weeks of age, MMTV-PyMT mice were housed with access either to wirelessly recording running wheels or locked control wheels. Running distances and tumor volumes were recorded. At 12 weeks, mice were sacrificed and mammary glands were histologically staged and pulmonary metastases were quantified. In a follow up study, pre-trained mice were injected intravenously with tumor cells derived from the PyMT model and after an additional 10 weeks of voluntary running, pulmonary metastases were quantified.

Results: PyMT mice ran significantly more than wildtype mice (6.4 vs 3.4 km/day). No significant effects of voluntary running on tumor- initiation, volume or stage were found. However, a trend for reduced metastasis was observed. Significant reductions in pulmonary metastasis frequency were found in runners after intravenous injections of tumor cells. Metastases of running mice displayed a reduced proliferation score.

Discussion: In this aggressive breast cancer model, an average of 6 km/day of voluntary running produces little effect on tumor formation and growth. However, the findings suggest that physical activity has impact on the metastatic process.

Citation Format: Helene Rundqvist, Sara Mijwel, Emil Ahlstedt, Carolin Lindholm, Carina Strell, Pernilla Roswall, Kristian Pietras, Randall Johnson, Arne Ostman. Effect of voluntary running on metastasis in a mouse model of breast cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A65.
Abstract B01: Body fatness throughout life and the incidence of endometrial cancer
Authors: Dougan Marcelle M. , Vivo Immaculata De , Tworoger Shelley S. , Hankinson Susan E. , Michels Karin B.
Published: May 2019

Background: Although adult obesity is known to increase endometrial cancer (EC) risk, evidence for the role of childhood obesity is limited. We prospectively examined the association between body fatness throughout the life-course and EC risk.

Design: Participants, 47,289 members (527 cases) of the Nurses' Health Study (NHS), and 105,386 members (130 cases) of the Nurses' Health Study II (NHS II) recalled their body fatness at ages 5, 10, and 20 using a nine-level pictogram. Childhood and adolescent body fatness were the average between ages 5 and 10, and ages 10 and 20, respectively. We obtained weight from biennial questionnaires and calculated relative risks (RR) of EC using Cox proportional hazards models. All statistical tests were two-sided.

Results: In the NHS, body fatness was associated with EC at age 10, adolescence, age 20, and adulthood, but not at age 5 or childhood (RR for EC comparing most overweight to least overweight in adolescence was 1.51, 95% CI 1.08-2.11, Ptrend 0.02). For NHS II, the associations were stronger (RR, comparing most overweight to least overweight in adolescence was 2.91, 95% CI 1.83-5.98, Ptrend <0.001). However, after adjusting for current body mass index (BMI), none of the associations persisted (NHS: RR was 0.93, 95% CI 0.65-1.32 Ptrend 0.40; NHS II: RR was 1.14, 95% CI 0.59-2.20, Ptrend 0.73). The association between adult BMI and EC was similar across both cohorts.

Conclusion: These findings indicate that body fatness in early life is not independently associated with endometrial cancer risk.

Citation Format: Marcelle M. Dougan, Immaculata De Vivo, Shelley S. Tworoger, Susan E. Hankinson, Karin B. Michels. Body fatness throughout life and the incidence of endometrial cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B01.