bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A133: Racial/ethnic differences in serum sex steroid hormone concentrations in a nationally representative sample of U.S. adolescent males
Authors: Lopez David S. , Rohrmann Sabine , Rifai Nader , Platz Elizabeth
Published: May 2012

Background: Contrary to the hypothesis that the racial/ethnic disparity in prostate cancer (PCa) has a hormonal basis, we did not observe a statistically significant difference in serum testosterone concentration between non-Hispanic black (NHB) and non-Hispanic white (NHW) adult men in the nationally-representative Third National Health and Nutrition Examination Survey (NHANES III), although NHB men had a higher estradiol level. Unexpectedly Mexican-American men (MA) had the highest testosterone level. In this study, we evaluated racial/ethnic differences in hormone concentrations during puberty, the time of prostate maturation.

Methods: We measured serum testosterone, estradiol, and sex hormone binding globulin (SHBG) concentrations by immunoassay for 161 adolescent males aged 12–19 who participated in the morning examination of Phase I of NHANES III. Free testosterone and free estradiol were estimated. Geometric mean concentrations were compared by race/ethnicity using linear regression adjusting for age, Tanner (puberty) stage, percent body fat (%BF), waist circumference (WC), physical activity, smoking, and the other hormones.

Results: In 12–15 year olds, MA males had the highest total and free testosterone concentration (MA vs NHB: P<0.05). In 16–19 year olds, the pattern for total testosterone was similar to that for younger adolescents, whereas free testosterone did not differ by race/ethnicity. In 12–15 year olds, MAs had the lowest total (MA vs NHW: P<0.05) and free estradiol. In 16–19 year olds, NHBs had the highest and MAs the lowest total and free estradiol levels (NHB vs MA: P<0.05).

Conclusion: MA male adolescents had the highest testosterone and older NHB male adolescents had the highest estradiol levels, patterns similar to adult males in NHANES III.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A133.
Abstract A17: Using high-throughput imaging cytometry to unmask the true nature of oral lesions in a high-risk community
Authors: Poh Catherine F.Y. , Guillaud Martial , Zhang Lewei , MacAulay Calum , Rosin Miriam
Published: May 2012

Vancouver's Downtown Eastside is a high-risk community for oral cancer. Previous study has shown its prevalence of tobacco and alcohol consumption and high incidence of oral cancer (one cancer identified in 150 residents screened). Additionally, oral infection and inflammation are commonly seen in this community. In British Columbia, we are evaluating several technologies and their interactions for the screening and early detection. Direct fluorescence visualization (FV) has shown its high sensitivity for the detection of oral cancer or precancer, but can also highlight other oral conditions which are commonly seen within community setting. We start to look at the utility of imaging cytometry as an adjunct tool in oral cancer screening. There is an urgent need to develop an effective strategy for oral cancer screening in such a high risk community.

Objectives: 1) To using imaging cytometry to measure the altered nuclear phenotype (cNPS) and 2) To see if cNPS can increase the accuracy of using FV only for oral screening.

Methods: From 2004/11–2009/2, we have collected 355 exfoliative cell samples using a small curved interdental tooth brush from this high-risk community. Samples were spun down onto slides, the DNA quantitatively labeled and automatically scanned by the cyto-savant®. For each object (nucleus/debris) imaged ∼110 features were calculated and used by a cell recognition decision tree to differentiate cells from debris.

Results: Among 355 brushings, 4 from cancerous sites, 90 from non cancerous common oral lesions (60, trauma; 28, inflammation; 12, infection), and from tongue with no lesion under clinical white light and FV examinations. Using previously trained algorithm with 84% sensitivity and 97% specificity to examine these samples, there was no difference between gender, age groups, smoking habit, and immune status (presence of HIV infection). This algorithm can correctly identified 3 out of 4 high-grade lesions and 89% normal cases. For those non-cancerous common oral lesions, using FV followed with the examination of cNPS at the FV loss area can drastically increase the accuracy from 10% to 83% (trauma, 13% to 90%; inflammation, 6% to 78%; infection 0% to 75% respectively).

Conclusion: The pilot results indicate support the potential usage of the combination of direct FV and imaging cytometry in oral cancer screening in a high-risk community.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A17.
Abstract A35: Chemoprevention of colon carcinogenesis in F344 rats by Se,Se′-1,4-phenylenebis(1,2-ethanediyl)bis-isoselenourea (PBISe) a novel analog of PBIT, an iNOS inhibitor
Authors: Janakiram Naveena B. , Mohammed Altaf , Ravillah Durgadevi , Choi Chang In , Zhang Yuting , Desai Dhimant , Amin Shantu , Rao Chinthalapally V.
Published: May 2012

Inducible nitric oxide synthase (iNOS) is potential target for inflammation and cancer. Previously, we have shown that S,S′-1,4-Phenylenebis(1,2-ethanediyl)bisisothiourea (PBIT) inhibit colon carcinogenesis induced by azoxymethane (AOM). Although, colon cancer inhibitory efficacy of PBIT has been significant, selective iNOS inhibitors do not completely abrogate NO production due to the exogenous bioavailability and NO generation by eNOS in tumor tissues. To create an iNOS selective and multi-targeted molecule, we have developed a novel isosteric analogue of PBIT, namely PBISe in which sulfur was replaced with selenium. We examined the chemopreventive efficacy of PBISe on AOM-induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as end point. At seven weeks of age, rats (12/group) were fed the control diet (AIN 76A) and colonic ACF were induced by AOM. Three days after second AOM treatment, rats were fed the diets containing 0, 10 and 20 ppm of PBI-Se and continued on the respective diets for 8 weeks before ACF were evaluated histopathologically. Furthermore, PBISe (0–12 µM) and PBIT (0 – 100 µM) were studied for the markers of growth inhibition and induction of apoptosis in the human colon cancer CaCo2 cell line. In addition, inhibitory effect of PBISe and PBIT on proinflammatory signaling molecules iNOS, IL-8 and IL-6 were studied by RT-PCR. Results suggest that dietary administration of 10 and 20ppm of PBISe significantly suppressed AOM-induced total colonic ACF formation (32 – 41%, p< 0.001), and multi crypt (4 or more) aberrant foci (29 – 47%, p< 0.001) respectively. Dietary PBISe suppressed AOM-induced colonic ACF in a dose-dependent manner and it required less than half the dose of PBIT to inhibit total ACFs in rats. Both PBIT and PBISe in CaCo2 cells induced dose-dependent apoptosis. PBIT and PBISe treatment on CaCo2 cells showed significant decrease in cell cycle protein cyclin D1 (∼70%, p<0.0001) and iNOS (∼99%, p<0.0001). Also, treatment with PBIT (30 and 60 M) significantly decreased cytokine induced IL-6 at both the doses whereas PBISe had no such effect. PBIT significantly attenuated the LPS-induced IL-6 and IL-8 production in a dose dependent manner. Whereas, PBISe significantly increased IL-8 and attenuated IL-6 production in CaCo2 cells suggesting differential modulatory effects on immune cells/inflammatory pathways. Incorporation of selenium into the structure of PBIT has provided the agent with additional novel cytotoxic and immunologic properties. Results from in vitro and in vivo bioassay clearly suggest that PBI-Se could be further developed for prevention and treatment of colon cancer.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A35.
Abstract A39: In vitro mechanisms of cadmium-induced apoptosis in human liver carcinoma (HEPG2) cells
Authors: Skipper Anthony C. , Tchounwou Paul B. , Yedjou Clement
Published: May 2012

Cadmium is a heavy metal that has been shown to manifest its toxicity in humans and animals. Many documented in vitro studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Diseases like autoimmune thyroidism are thought to be caused, in large part, by overexposure to cadmium. Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, the mechanisms of the carcinogenic activity of cadmium is not clearly defined. Therefore, the purpose of this study was to elucidate some of the molecular mechanisms that are involved in cadmium-induced toxicity in human liver carcinoma (HepG2) cells. To achieve this goal, we performed the MTT assay to measure cell viability. Annexin V assay and DNA fragmentation analysis were performed for early and late apoptosis, respectively. The result of MTT assay indicated that cadmium induces toxicity to HepG2 cells in a dose-dependent manner, showing a 24 h-LD50 of 3.6 µg/mL cadmium chloride. Similarly, a strong dose-response relationship (p < 0.05) was obtained in connection with cadmium chloride-induced apoptosis. Cadmium chloride-induced apoptosis was characterized by a significant increase in the percentages of annexin-V positive cells, as well by the occurrence of nucleosomal DNA fragmentation. In summary, this study indicated cadmium chloride is highly cytotoxic to HepG2 cells. This cytotoxic effect may be mediated at least in part through phosphatidylserine externalization and occurrence of nucleosomal DNA fragmentation.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A39.
Abstract A58: Cul3-mediated Nrf2 ubiquitination and ARE activation are dependent on the partial molar volume at position 151 of Keap1
Authors: Eggler Aimee L. , Small Evan , Hannink Mark , Mesecar Andrew D.
Published: May 2012

Nrf2 is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the antioxidant response element (ARE). Nrf2 is repressed by the cysteine-rich Keap1 protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3-mediated ubiquitination complex. Several promising chemopreventive agents, including sulforaphane, activate Nrf2 in Keap1 C151-dependent manner. We find that modification of C151 of human Keap1 by mutation to a tryptophan relieves the repression by Keap1 and allows activation of the ARE by Nrf2. Keap1 C151W has a decreased affinity for Cul3, and can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. A series of 12 mutant Keap1 proteins, each containing a different residue at position 151, was constructed to explore the chemistry required for the effect. The series reveals that the extent to which Keap1 loses the ability to target Nrf2 for degradation, and hence the ability to repress ARE activation, correlates well with the partial molar volume of the residue. Other physico-chemical properties do not appear to contribute significantly to the effect. Based on this finding, a structural model of the Keap1-Cul3 binding interface was constructed to investigate the potential mechanism of action of a tryptophan or other group at position 151. Several residues surrounding position 151, K131, R135 and K150, were observed in the model to be close enough to be involved in a steric clash with the tryptophan. Keap1 proteins containing these residues mutated to alanine, along with C151W, were evaluated for their ability to repress Nrf2. We find that none of mutations were able to restore the ability of Keap1 C151W to repress Nrf2. Additional residues are being investigated in effort to determine which residue(s) might be responsible for translating the increase in partial molar volume at position 151 to a lack of Nrf2 repression. This work has significant implications for how chemopreventive electrophiles that modify C151 disrupt the repressive function of Keap1.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A58.
Abstract A65: Caspase 14 is a target of black-raspberry-mediated inhibition of human cervical cancer cell proliferation
Authors: Zhang Zhaoxia , Knobloch Thomas J. , Seamon Leigh G. , Backes Floor J. , Stoner Gary D. , Paskett Electra D. , Cohn David E. , Fowler Jeffrey M. , Weghorst Christopher M.
Published: May 2012

Cervical cancer is the second most common female cancer worldwide and the seventh leading cause of cancer death in women. While significant advances have been made in early detection, it remains a challenge to manage pre-invasive and invasive cervical lesions. However, the long latency of cervical cancer development allows for the investigation and utilization of preventive and therapeutic interventions, including chemopreventive approaches. Phytochemical-based cancer chemoprevention and the role of bioactive food components have attracted significant interest due to their dramatic anti-proliferative and anti-tumorigenesis effects observed in preclinical studies. We have previously demonstrated that an extract of lyophilized black raspberries (LBR, Rubus occidentalis) inhibited the proliferation of human cervical cancer cell lines: HeLa (HPV16−/HPV18+, adenocarcinoma), SiHa (HPV16+/HPV18−, squamous cell carcinoma) and C-33A (HPV16−/HPV18−, squamous cell carcinoma) in a dose- and time-dependent manner. Here we investigate the modulation of apoptotic pathways as a potential mechanism. Expression profiling of 93 apoptosis-related genes was performed with the Applied Biosystems' TaqMan Gene Signature Human Apoptosis Array in HeLa, SiHa and C-33A human cervical cancer cells treated with vehicle control (0.02% DMSO) or LBR (200µg/mL) for 1 and 3 days. The following genes were differentially expressed (≥2-fold change) in a manner favorable to cancer prevention following LBR treatment: CARD9 (+4.4) and BCL2L10 (−4.0) in HeLa cells; BIRC1 (−2.3) and CASP14 (+4.2) in SiHa cells; CARD15 (+3.4), TNFRSF1B (+2.8), TNFRSF1A (+2.3), FADD (+2.3), BBC3 (+2.1), BOK (+2.1), RELB (+2.1), IKBKG (+2.0), HTRA2 (+2.0), DEDD2 (+2.0), BAD (+2.0) and BAX (+2.0) in C-33A cells. Two candidate genes from each cell line were chosen for subsequent validation: CARD9 and BCL2L10 in HeLa cells, BIRC1 and CASP14 in SiHa cells, FADD and BAX in C-33A cells. From these selected candidate genes, only CASP14 was validated as a >2-fold expression change (+5.1) following LBR exposure in SiHa cells. CASP14 mRNA expression was undetectable (>40 Ct values) in both HeLa and C-33A cells. Caspase 14, a cysteine-aspartic proteases, is directly involved in epithelial cell differentiation, and only indirectly with canonical apoptotic pathways. Caspase 14 plays a role in epithelial cell malignant transformation, and is progressive loss during cervical cancer progression. Consequently, up-regulation of CASP14 expression by LBR in cervical cancer cells may provide a potential mechanism for attenuating cervical carcinogenesis and progression. Further studies will define the contribution of CASP14 mRNA and protein up-regulation following LBR exposure in cervical cancer cells.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A65.
Abstract A72: Punicic acid, a fatty acid from pomegranate seed oil, inhibits breast cancer cell proliferation
Authors: Grossmann Michael E. , Mizuno Nancy K. , Schuster Todd , Cleary Margot P.
Published: May 2012

Introduction: Pomegranate (Punica granatum) is a well-known fruit used for alternative medicine. Various pomegranate extracts are utilized as supplements with a wide variety of purported health benefits including anticancer actions. These supplements contain a number of different components that may either activate or inhibit estrogen's action. Additionally factors associated with pomegranate fruit or extracts may lower oxidation of LDL cholesterol, reduced arterial plaques, lower oxidative stress, enhanced wound healing, inhibition of angiogenesis and tumor proliferation and increased tumor apoptosis. However, these studies have been conducted with fruit, seeds, pericarp or partially purified pomegranate extracts making it hard to determine what the active component(s) may be. Punicic acid is an omega-5 long chain polyunsaturated fatty acid found in pomegranate seed oil. A number of long chain fatty acids have been reported to have cancer preventive actions. Here we investigated the potential ability of punicic acid to affect growth of both an estrogen insensitive breast cancer cell line (MDA-MB-231) and an estrogen sensitive cell line developed from the MDAMB-231 cells (MDA-ER 7).

Methods: The two breast cancer cell lines were cultured in vitro in the presence of various amounts of punicic acid, conjugated linoleic acid, α-linolenic acid and other substances to evaluate cell proliferation, apoptosis, mitochondrial membrane permeability and cell cycle.

Results: We found that 40 µM punicic acid inhibited proliferation of MDA-MB-231 and MDA-ER 7 cells 92% and 96% respectively compared to untreated cells. Furthermore, punicic acid induced apoptosis in the MDA-MB-231 and MDA-ER 7 cells by 86% and 91% respectively compared to untreated control cells. Punicic acid also disrupted mitochondrial membrane potential of both cell lines. We next investigated whether lipid oxidation was required for the function of punicic acid by adding 20 µM of the antioxidant tocotrienol to the assays. This resulted in reversal of the effects of punicic acid on proliferation inhibition, apoptosis and disruption of the mitochondrial membrane potential in both the MDA-MB-231 and MDA-ER 7 cells. Finally, we evaluated the role of PKC signaling in the anticancer effects of punicic acid by performing proliferation assays in the presence of the PKC inhibitor bisindolymaleimide I. Proliferation inhibition by punicic acid was partially blocked in both the MDA-MB-231 and MDA-ER 7 cells.

Conclusions: Our in vitro assays indicated that punicic acid inhibited both estrogen sensitive and estrogen insensitive cell lines equally. Additionally the results indicate that the antiproliferative effect of punicic acid on human breast cancer cells appears to be at least partially dependent on lipid peroxidation and the PKC pathway.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A72.
Abstract A73: Bladder cancer inhibition by allyl isothiocyante
Authors: Bhattacharya Arup , Tang Li , Geng Feng , Paonessa Joseph D. , Chen Shang C. , Wong Michael K.K. , Zhang Yuesheng
Published: May 2012

Nearly all cancers of the urinary bladder originate from its inner surface (epithelium). While most bladder cancers are diagnosed at an early stage, recurrence rate is extremely high. There is an urgent need for agents capable of inhibiting bladder cancer development and recurrence. Allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, was previously shown to kill bladder cancer cells in vitro. Our objective was to evaluate the chemopreventive potential of AITC against bladder cancer. The anticancer activities of AITC were assessed using multiple bladder cancer cell lines in vitro and two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). Its toxicity toward normal human bladder epithelial (NHBE) cells was also examined. Pharmacokinetic study of AITC and histological examination of normal and malignant bladder tissues of AITC-treated rats were undertaken as well.

Proliferation of bladder cancer cells was potently inhibited by AITC (IC50 of approximately 3 µM), which was associated with G2/M arrest and apoptosis. AITC was markedly less toxic to NHBE cells (IC50 of 69 µM). Low oral dose of AITC (1 mg/kg), starting one day after cancer cell inoculation significantly inhibited the development of orthotopic bladder cancer, but was ineffective against subcutaneous xenografts of the same cancer cells. This differential effect was explained by our finding that urinary concentrations of AITC equivalent were 2–3 orders of magnitude higher than that in the plasma, and that its levels in the orthotopic bladder cancer tissues were also 3 orders of magnitude higher than that in the subcutaneous cancer tissues. Thus, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development in vivo. Besides its potential use for prevention of primary bladder cancer, AITC appears to represent a novel and very attractive approach in the management of recurrence of superficial bladder cancer, since all currently available intravesicle therapies against bladder cancer recurrence mandate urethral catherization. In addition, this new knowledge opens the possibility for adjuvant or multimodality combination approaches for the prevention and treatment of bladder cancer. Supported by NCI grant CA124627.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A73.
Abstract A74: Inhibition of azoxymethane-induced preneoplastic lesions in the rat colon by a novel resistant starch cooked by different methods
Authors: Zhao Yinsheng , Hasjim Jovin , Ai Yongfeng , Jane Jay-lin , Birt Diane F.
Published: May 2012

The purpose of this study was to test the inhibitory effects of a novel resistant starch cooked by two different methods on azoxymethane (AOM)-induced colon carcinogenesis in rats. The novel resistant starch (RS)(patent pending) was processed from commercial high amylose cornstarch. A normal cornstarch (CS) and the high amylose cornstarch (HA) were used as negative and positive control starch groups, respectively. Two cooking methods were applied to all the three starches: (1) making each starch into bread using a standard bakery procedure (cB). (2) using boiling water, high moisture cooking method (cW). Then the starches were mixed with other ingredients based on AIN-93 formulations into 6 rat diets: bread normal-cornstarch diet (cB-CS), bread high-amylose-cornstarch diet (cB-HA), bread novel-resistant-starch diet (cB-RS), boiling-water-high-moisture normal-cornstarch diet (cW-CS), boiling-water-high-moisture high-amylose-cornstarch diet (cW-HA), and boiling-water-high-moisture novel-resistant-starch diet (cW-RS). Six groups of 5-week-old male Fischer 344 rats including 15 animals each were injected with two doses of 20 mg/kg bw AOM one week apart and fed the above diets respectively. Another six groups of male Fischer 344 rats with 5 animals in each group were injected with saline and fed the same six kinds of diets as the AOM treated groups. The rats were fed for 8 weeks after the second injection and then killed. Caecum weight and pH, Aberrant Crypt Foci (ACF) and Mucin Depleted Foci (MDF) were investigated. ACF and MDF were only seen with AOM treatment. The ACF numbers for cB-CS, cB-HA, cB-RS, cW-CS, cW-HA, and cW-RS groups were 29, 29, 17, 225, 256, and 121, respectively. The MDF numbers for the above diet groups were 6.1, 4.9, 1.9, 10.7, 8.7 and 2.1, respectively. ACF and MDF numbers were significantly reduced in rats fed novel resistant starch diet in comparison with rats fed the other two diets (P<0.0001). When comparing the two cooking methods, the cB diet groups also showed a significantly decrease in preneoplastic lesion numbers compared with the cW diet groups (P<0.0003). Increased caecum weight and decreased caecum pH were also observed in the novel resistant starch diet group in comparison with the other two diet groups (P<0.05). These results suggested that the novel resistant starch, which is less digestible than regular cornstarch or commercial high amylose cornstarch, may inhibit colonic carcinogenesis. The cooking method could also be important since the bread baking procedure showed significantly more effectiveness in the inhibition than the boiling water high moisture method. The inhibition might be related to increased caecal fermentation.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A74.
Abstract A79: Human breast tissue bioavailability of topically applied limonene
Authors: Miller Jessica A. , Thomson Patricia , Hakim Iman A. , Lopez Ana Maria , Vining Donna , Chew Wade M. , Chow H-H Sherry
Published: May 2012

Purpose: Limonene is a monocyclic monoterpene found at high concentration in citrus peel oil and has demonstrated anti-cancer effects in preclinical studies of mammary carcinogenesis. However, the effective oral dose determined in rodents extrapolates to a human dose that may not be feasible for long-term consumption. Limonene is highly lipophilic and has been long explored as an enhancer for percutaneous absorption of pharmaceutical drugs, including tamoxifen. Preliminary work from our group demonstrated that topically applied limonene is absorbed through the mouse skin and accumulates in the mammary glands.

Methods: We conducted a pilot clinical study to determine whether limonene would be bioavailable in the breast following topical application. In the first study phase, we recruited 19 healthy women to apply limonene containing massage oil to the breast daily or 3x/wk. Nipple aspirate fluid (NAF) and plasma samples were collected before and after 4 weeks of limonene massage application. Sample limonene concentrations were determined using gas chromatography-mass spectrometry. In the second study phase, we recruited 25 healthy women to undergo 4 weeks of daily limonene massage oil application to the breast. Potential agent effect biomarkers were determined in NAF and plasma collected before and after the limonene massage application.

Results: In samples collected from the first study phase, no significant increase in NAF and plasma limonene levels was observed following the limonene massage application, possibly because limonene deposits in the fatty breast tissue with minimal secretion to NAF or systemic circulation. Changes in agent effect biomarkers in NAF, including TGF-beta, EGF, and adiponectin, were evaluated in the second study phase for determination of the breast tissue limonene bioavailability. There were no consistent changes in the agent effect biomarkers overall or in pre-menopausal women following the limonene massage application. However, among the post-menopausal women (n =8), there were significant increases in NAF levels of TGF-beta (p = 0.005) and EGF (p = 0.032), and there was an increasing trend in adiponectin (p = 0.164, n=5 due to limited NAF volume).

Conclusions: We conclude that breast massage application of limonene containing massage oil did not result in consistent changes in limonene secretion to the NAF and the potential drug effect biomarkers in NAF. However, limonene massage application increased the NAF expression of TGF-beta and EGF in post-menopausal women, indicative of the intervention effects in the breast tissue. Further studies are needed to explore the potential effects of topical limonene massage intervention on carcinogenesis biomarkers in a larger cohort of post-menopausal women. Supported by Department of Defense, BCRP Idea Award, BC061529

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A79.
Abstract A91: Racial and urban/rural disparities in treatment of non-small cell lung cancer among Medicare beneficiaries in Alabama, 2000–2003
Authors: Steele Conola B. , Pisu Maria , Richardson Lisa C.
Published: May 2012

Introduction: In 2005, non-small cell lung cancer (NSCLC) incidence and mortality rates in Alabama (77.5 per 100,000 population and 65.0, respectively) exceeded corresponding rates in the U.S. (67.7 and 52.8, respectively). Within Alabama, incidence and mortality vary by race, urban/rural residence, and other demographic characteristics. We examined racial (black versus white) and geographic (urban versus rural residence) differences in stage at diagnosis of NSCLC and treatment received (i.e., surgery, chemotherapy, radiation therapy) among Medicare beneficiaries in the state.

Methods: We linked Alabama State Cancer Registry data with Medicare claims to identify beneficiaries with NSCLC (either American Joint Committee on Cancer [AJCC] stages I–IV or unknown stage) diagnosed in 2000–2003. We examined distributions of NSCLC by race and geography, and applied multivariate logistic regression to compute odds of receiving stage-specific treatment among beneficiaries.

Results: There were 3,929 beneficiaries with NSCLC: 86.7% were white, 13.3% black, 50% resided in the state's 55 rural counties, and 50% in the remaining12 urban counties. Blacks and whites in urban counties had slightly higher proportions of resectable NSCLC (stages I, II, IIIA) (36.2% and 47.2%, respectively) compared with blacks and whites in rural counties (31.2% and 44.2%, respectively). Proportions of unknown stage were higher among blacks and whites in rural counties (38.9% and 29.7%, respectively) compared with blacks and whites in urban counties (24.3% and 21.2%, respectively). Blacks had a 37% lower odds of undergoing surgery than whites (OR, 0.63; 95% confidence interval [CI] 0.41–0.96). This racial disparity was greater in rural counties, where the odds of blacks undergoing surgical resection were 52% lower than the odds for whites (OR, 0.48;CI 0.28–0.84). Among black beneficiaries who underwent surgery, those residing in urban counties had higher proportions of receipt of any adjuvant therapy (39.6%) than those in rural counties (19.2%). Among surgically-treated whites, the receipt of any adjuvant therapy was similar in both types of counties (approximately 32%).

Conclusions: Disparities in receipt of treatment for NSCLC in Alabama exist. Future studies should focus on the reasons for these differences, which may be associated with access to health care in different counties, patients' knowledge of and beliefs about available treatment for their cancer, and physicians' attitudes toward treating patients with lung cancer.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A91.
Abstract A95: Socioeconomic, demographic, lifestyle, anthropometric, and clinical correlates of high Gleason score prostate cancer in U.S. veterans
Authors: Cyrus-David Mfon S.
Published: May 2012

Socioeconomic status has not been consistently associated with prostate cancer outcomes, and the risk factors of aggressive prostate cancer have not been fully characterized. Therefore, I assessed how socioeconomic status and demographic, lifestyle, anthropometric, and clinico-pathological characteristics are associated with low- (i.e. ≤6), intermediate- (i.e. 7), or high-risk (i.e. ≥8) Gleason scores for prostate cancer at diagnosis. As part of the Prostate Cancer Stage Study, a cross-sectional pilot study conducted between 2006 and 2008, I recruited 248 U.S. male veterans (Caucasians, n=137; Latinos, n=18; African American, n=90; unknown, n=3) with histopathologically confirmed prostate cancer who lived in Houston, Texas, or its surrounding counties. The subjects were interviewed and anthropometric measurements were taken. Chi-square, analysis of variance, and univariate logistic regression procedures were used to compare subjects with low-, intermediate-, and high-risk Gleason scores by covariates. Patients with low-risk Gleason scores were more likely to have first-degree relatives with prostate cancer (odds ratio [OR], 2.09, 95% confidence interval [CI], 1.03–4.24), higher serum prostate-specific antigen levels before treatment (OR, 0.19, 95% CI, 0.10–0.38), and higher T classifications (OR, 0.06, 95% CI, 0.02–0.28). Patients with intermediate-risk Gleason scores were more likely to live in metropolitan counties (OR, 2.36, 95% CI, 1.06–5.22) with median household incomes between $40,000 and $49,999 (OR, 2.14, 95% CI, 1.12–4.09). High-risk patients were more likely to have had body weights greater than or equal to the median (OR, 2.61, 95% CI, 1.20–5.65), and to have been obese (OR, 4.78, 95% CI, 1.28–17.85) when they were 25 years old. They also were more likely have higher serum prostate-specific antigen levels before treatment (OR, 10.9, 95% CI, 4.74–25.18) and higher T classifications (OR, 7.14, 95% CI, 2.87–17.74) compared with other subgroups. They also tended to be current smokers (OR, 2.93, 95% CI, 0.94–9.19) relative to Gleason scores categories, with the patients who never smoked serving as the referent group, although this result was not statistically significant. Finally, in this study population of patients, who were recruited from an equal-access setting, their racial/ethnic backgrounds were not associated with the clinico-pathological features at diagnosis. Therefore, I concluded that preventing obesity in young adults, improving access to, and use of prostate cancer prevention services, especially for men who have a family history, and inner city residents, would be beneficial.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A95.
Abstract B111: Obesity is associated with worse outcome in colon cancer survivors
Authors: Sinicrope Frank A. , Foster Nathan R. , Sargent Daniel J. , O'Connell Michael J. , Rankin Cathyrn
Published: May 2012

Purpose: Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) upon the outcome of colon cancer survivors and its relationship to gender remains unknown.

Experimental Design: BMI (kg/m2) was calculated and categorized in patients with TNM stage II and III colon carcinomas (n= 4,381) enrolled in 7 randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Cox proportional hazards modeling was used to determine the association of BMI with disease-free and overall survival.

Results: Among colon cancer patients, 868 (20%) were obese (BMI ≥30 kg/m2) of which 606 were class 1 (BMI 30–34 kg/m2) and 262 were class 2,3 (BMI ≥35 kg/m2). Obese versus normal-weight patients were more likely to be younger, have distal tumors, show intact DNA mismatch repair (MMR), and have increased lymph node metastases (p <0.017). The association of BMI and MMR status was dependent upon patient age (p= 0.031). In a multivariate analysis, BMI was significantly associated with both disease-free (p=0.030) and overall survival (p=0.0017). Men with class 2,3 obesity showed reduced overall survival compared to normal weight men [HR 1.35 (1.02, 1.79); p=0.039]. Women with class I obesity had reduced overall survival [HR 1.24 (1.01, 1.53), p=0.045] compared to normal weight women. BMI was not predictive of therapeutic benefit.

Conclusions: Obesity is associated with intact DNA mismatch repair status and was an adverse, independent prognostic variable in colon cancer survivors. Interventions to reduce obesity have the potential to improve patient outcomes in colon cancer survivors.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B111.
Abstract B116: Association between CYP7A1 loci and the risk of proximal colon cancer in the Japanese
Authors: Matsuo Keitaro , Ito Hidemi , Hosono Satoyo , Watanabe Miki , Kawase Takakazu , Suzuki Takeshi , Hirai Takashi , Yatabe Yasushi , Tanaka Hideo , Tajima Kazuo
Published: May 2012

Introduction: Bile acids have long been implicated in the etiology of colorectal carcinogenesis by their genotoxicity as well as cytotoxicity. Cholesterol 7-alfa-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7-alfa-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. Recently, an association between a polymorphism (-204A>C, rs3808607) in CYP7A1 and proximal colon cancer/adenoma has been reported, which was not observed with distal colon or rectal cancer/adenoma. In this case-control study, we examined the association between haplotypes of CYP7A1 and proximal or distal colon/rectal cancer risk in a Japanese population.

Methods: Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age- and sex-matched non-cancer controls. We examined five loci, including rs3808607, by TaqMan method. Impact of each locus or haplotype were evaluated according to subsite by polytomous logistic regression models adjusted for potential confounders including age, sex, regular exercise, family history of colorectal cancer, body mass index, drinking habit and folate consumption.

Results: In locus-specific analyses, we saw no association with rs3808607 for any subsite. Rs11786580 showed a statistically significant positive association with proximal colon cancer, while association was not seen in distal colon and rectal cancer. Haplotype analyses revealed that the TAAGG haplotype was positively associated with proximal colon cancer [confounder-adjusted odds ratio: 1.72 (95% confidence interval: 1.10–2.71), p=0.018] but not with distal colon and rectal cancer combined. This association was consistently observed in analyses stratified by potential confounders. Conclusion: Our results indicate that CYP7A1 plays a role in the carcinogenesis of colorectal cancer specifically in the proximal colon. Confirmation of this association in other epidemiologic studies and biological evaluation of the TAAGG haplotype are warranted.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B116.
Abstract B128: Geographic and socioeconomic variations in colorectal cancer incidence in the prospective NIH-AARP Diet and Health study
Authors: Chyke Doubeni A. , Laiyemo Adeyinka O. , Lian Min , Park Yikyung , Li Wenjun , Schootman Mario , Schatzkin Arthur
Published: May 2012

Background: Persons from lower socioeconomic backgrounds have higher exposure to risk factors for, and higher mortality rate from, colorectal cancer (CRC), but there is a paucity of published population-based studies on the relationship between neighborhood socioeconomic context and CRC incidence. In this study, we used national prospective data to determine: 1) whether CRC incidence varied according to area-level socioeconomic context; and 2) if area-level differences in incidence are explained by clustering of CRC risk factors.

Methods: We used data from the NIH-AARP Diet and Health Study, a prospective cohort of 566,402 persons residing in 6 US states and 2 metropolitan areas who were 50–71 years of age at baseline (1995–1996). Detailed data on diet, lifestyle and medical history were collected using questionnaires. Cancer incidence was ascertained from tumor registries through December 31, 2003. Participants were linked to the 2000 US Census data at the tract level. We used principal component factor analyses to derive an index of neighborhood socioeconomic deprivation from 10 census variables about education, poverty, employment and occupation. We restricted the analyses to 319,057 men and 214,298 women who did not have history of CRC at baseline and had complete data including valid geocoded information.

Results: In single predictor Cox models with frailty, compared to persons residing in the lowest quintile of the deprivation index, those in the most deprived census tracts had a higher incidence of CRC (HR=1.27; 95% confidence interval [CI]: 1.16–1.40 for men and HR=1.32, CI: 1.15–1.52 for women). This increased risk was robust to adjustments for age, race-ethnicity and family history of colon cancer, body mass index, physical activity and dietary variables including calcium intake, smoking and a history of diabetes (HR: 1.13, CI: 1.03–1.24) for men and HR: 1.17, CI: 1.01–1.34 for women) and to further adjustment for use of non-steroidal inflammatory agents (HR=1.18; CI 1.05–1.34) for men; and HR= 1.19, CI: 0.99–1.42 for women). Significant heterogeneity was observed for the incidence of CRC among census tracts for both men and women (likelihood ratio test p-value <0.001).

Conclusion: Our study found significant variation in the incidence of CRC by neighborhood of residence and neighborhood socioeconomic conditions after adjusting for recognized individual risk factors. Further studies are needed to explore other factors that may be associated with area-level differences in CRC incidence such as the use of screening.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B128.
Abstract B13: Arizona cancer research network analysis: Discovery to delivery
Authors: Leischow Scott , Provan Keith , Keagy Judy , Nodora Jesse
Published: May 2012

Background: Networks are frequently viewed as important for moving innovation beyond the boundaries of individual organizations, especially for enhancing translational research. This study used social network analysis to discover the extent and nature of involvement in collaborative relationships among the key organizations participating in cancer research activities in Arizona.

Methods: Data were collected in 2007 from 18 of 21 organizations involved in research in the Arizona Cancer Coalition, including academic institutions, private research institutes, and organizations dedicated to healthcare delivery, public health and support/advocacy. Key informants in each organization reported their collaborative relationships with every other organization in the Coalition for each of three types of cancer research activities, discovery, development, and delivery (3D). Data were analyzed using network analytic software (UCInet). Network measures included two global ‘whole network’ measures (network centralization and density) and one organizational level measure (degree centrality).

Results: The results of the network analysis showed the most highly connected, or dense, network ties were found when cancer research focused on delivery, closely followed by discovery. Organizational centrality in the development network is highly and positively correlated with both centrality in the discovery (r=.71, p<.001) and the delivery networks (r=.77, p<.001). In contrast, the relationship between centrality in the discovery and delivery network is quite weak (r=.33, not significant).These findings are consistent with the fact that discovery and delivery are at opposite ends of the research continuum, and thus, the central actors in each network are less likely to overlap. In addition, the importance of cancer research to an organization's mission is strong and positive, but only for the discovery (r=.61, p≤.01) and development (r=.51, p≤.05) networks

Conclusions: The research demonstrated how network analysis can be used to understand the extent to which organizations involved in cancer research are able to collaborate both within and across the 3D continuum. Findings suggested substantial differences in network involvement, depending on the type of research being conducted, while also demonstrating the key role played by a comprehensive cancer center in connecting organizations that might be involved in very different aspects of the research process.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B13.
Abstract B19: Complementary and alternative medicine use among postmenopausal breast cancer survivors: The Black Women's Health Study
Authors: Bright-Gbebry Mireille J.
Published: May 2012

Background: Complementary and alternative medicine (CAM) is widely used among women in the United States. However, there is limited knowledge about the use of CAM modalities in minority women despite the relationship of CAM use to cultural and health beliefs. We defined CAM use as the intake of natural herbs, vitamins and mineral products at least three days per week. The primary objectives of this study were to determine the prevalence of CAM usage in African American breast cancer survivors, and to compare the characteristics of users and nonusers.

Design: A cross-sectional study of breast cancer survivors who completed the 1999 Black Women's Health Study questionnaire and reported having been diagnosed with breast cancer by 1999. A total of 436 women were included in the analysis.

Results: Overall, 69% of breast cancer survivors compared to 59% noncases used one or more CAM products, including herbs, vitamins and minerals. Among breast cancer survivors the mean age for CAM users was 53.1 years compared to 51.3 years in nonusers. Among breast cancer survivor CAM users, garlic was the most widely used product (20.9%), followed by echinacea (12.6%) and gingko (11.7%). More CAM users chose a multivitamins supplement (53.9%) over a folic acid supplement alone (4.1%). Multivariate analysis determined that age (OR per year of age =1.05; 95% CI:1.02–1.08), and marital status (OR for single relative to married or living as married =0.33; 95% CI:0.15–0.70) were the factors significantly associated with CAM use among breast cancer survivors.

Conclusions: CAM use is common in postmenopausal African American breast cancer survivors. Our results are consistent with prevalence rates of 60–70% reported in studies of CAM use by women with breast cancer following diagnosis.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B19.
Abstract B37: Genetic screening of HNPCC
Authors: Koinuma Nobuo , Ito Michiya
Published: May 2012

Background and Objectives: Genetic testing and counseling for the patients with HNPCC (hereditary nonpolyposis colorectal cancer) are changing the cancer prevention strategies. However, the clinical evidence is still insufficient to make screening policy for at-risk carriers. In our study, while clarifying the economic effects/merits of genetic testing to HNPCC, the most appropriate age to start the screening from the viewpoint of health economics is presumed.

Materials and Methods: We developed systems model of colon cancer treatment along with Markov model, after sorting complicated clinical course of treatment by type. In the model, we presumed that the close relatives of the patient with HNPCC have genetic screening and continue undergoing the colonoscopic examination once a year afterward. We incorporated patients' data such as the cumulative morbidity of HNPCC, accumulated on the study groups of Japan into the systems model. When delaying cancer death by the intervention of genetic screening, the differences of the increment of the labor productivity of the prolonged period and that of the expense spent for the prevention and treatment is computed as an economic effect of cancer prevention.

Results and Discussion: The expense of genetic screening and endoscopy were $612 and $1,020 respectively. The stage distribution at the detection of colon cancer was as follows; I 36.8%, II 31.1%, III 19.2% and IV 12.9%. The utility value was assumed to be 0.8 in cost-utility analysis. In case of the male relative of the patient with HNPCC, the cost-benefit differences of genetic testing became large, if he would have genetic screening in his twenties. Hence, it became clear that genetic screening in younger age would have not a little meaning from cancer-economic point of view. Supposing he continued the examination in diagnostic phase in case of positive male, five-year survival rate after colon cancer treatment was as good as younger age when he underwent the genetic testing. In case of female, the rate of recovery is as good as younger age as well, but the cost-benefit differences became its maximum at her thirties rather twenties.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B37.