bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B31: Knowledge of cervical cancer screening among market women in sub-Saharan Africa: Nigerian experience
Authors: Gold Yemisi Cecilia
Published: June 2012

This study focuses on knowledge of cervical cancer screening among market women in selected markets in Ibadan, Nigeria. The objective of the study was to ascertain the knowledge of market women on cervical cancer. One hundred participants were selected from four markets in Ibadan, Nigeria to respond to a multi-choice–free response questionnaire designed to obtain information on their knowledge of cervical cancer screening. For this study, a non-experimental design was used to find out the level of knowledge of cervical screening method among the market women in Ibadan. The research design adopted for this study was purely descriptive. The research study was carried out in four major markets which are Bodija, Sango, Gate, and Gbagi markets in Ibadan. The sampling technique adopted in the study was the simple random sampling. The respondents were assured of the confidentiality of the data. On the respondent awareness of cervical cancer screening before, only 26 (26%) of the respondents strongly agreed that they have heard about cervical cancer screening while 15 (15%) were undecided and 59 (59%) have never heard about it, which means that majority of the respondents were not aware of cervical cancer screening. Furthermore, an importance of cervical screening was identified among 94 (94%) of women who were educated but 96 (96%) of these educated women have not been screened before, and 74 (74%) of the women were ready to be screened whether it is free or not. In addition, 97 (97%) of the women have a positive attitude that screening will help in detection of cervical cancer and only 48 (48%) are aware that early treatment of minor cervical cancer can prevent its reoccurrence. 92 (92%) agreed that it will be very good if the Government should campaign especially on mass media just like HIV (AIDs) for all to know about cancer of the cervix and also that there is treatment for it if it is detected on time, while 7 (7%) are undecided and 1(1%) disagreed. Considering whether the awareness of cervical cancer screening is low, 79 (79%) agreed that the awareness is very low and it will be good if the primary, secondary, and tertiary institutions can pass the information across to the community, while 18 (18%) were undecided and 3 (3%) disagreed. Nigerian government and policy makers need to sensitive the general public about cervical cancer screening and make the service widely available.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B31.
Abstract B43: The Vitamin D receptor and retinoid X receptor-alpha expression related to DNMT levels in a murine model of colitis
Authors: Knackstedt Rebecca , Moseley Vondina , Morris Jay , Wargovich Michael
Published: June 2012

Vitamin D3, whose functionality is controlled by signaling through the vitamin D receptor (VDR), plays a regulatory role in inflammation. To properly signal, VDR must heterodimerize with its signaling partner, Retinoid X Receptor (RXRα). When the signaling capability of Vitamin D3 goes awry, this mechanism of inflammation regulation is unchecked and cells are free to proliferate and release inflammatory signaling molecules. Inflammation and dysregulated Vitamin D3 signaling have been implicated in allowing the progression of colitis to cancer, but the mechanism by which this happens is poorly understood. Previous studies in our laboratory revealed that expression of RXRα is decreased in high-grade dysplasia in a mouse model of colon cancer. Whether RXRα or VDR are downregulated in human colitis remains to be clarified. The dextran sodium sulfate (DSS) model is a well-accepted animal model for human colitis, based on its histological similarity to human disease. Addition of azoxymethane (AOM), a carcinogen, is often utilized to encourage colon cancer development in mice with DSS-induced colitis.

As a first step, we examined the expression profiles of RXR and VDR in the DSS induced and the DSS/AOM induced mouse models of colitis. To achieve colitis with the DSS model, ten C57BL/6J mice were given 2% DSS for one week followed by a two week recovery period with water and five control mice received only water. This was repeated two times to simulate the remission and relapses evidenced in human colitis. Mice were sacrificed after the third cycle. For the AOM/DSS model, ten C57BL/6J mice were intraperitoneally (IP) injected with 10mg/kg of AOM (control mice were IP with saline) and allowed to recover for one week with water before being given the same DSS model as described above. Mice were killed after one cycle for the acute model or after three cycles for the chronic model. At sacrifice, colons were either swiss-rolled for IHC analysis of VDR, RXRα and PCNA or the mucosal layer was scraped for determination of VDR, RXRα and DNA methyltranferase (DNMT) expression and protein levels. We found that in both mouse colitis protocols VDR protein levels were decreased with altered levels of RXRα protein. In accord with these primary effects, we also found DNMT expression to be altered. We conclude that downregulation of key transcription factors by epigenetic mechanisms could play a role in murine colitis models. We are also investigating whether this find translates to one's risk for colon cancer

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B43.
Abstract B45: Inhibitory effects of fermented korean red ginseng on Helicobacter pylori-induced gastric inflammation and carcinogenesis
Authors: Kim Eun-Hee , Hong Kyung-Sook , Choi Ki-Seok , Ock Chan Young , Hong Hua , Han Young-Min , Paek Nam-Soo , Kim Sung-Soo , Hahm Ki Baik
Published: June 2012

Helicobacter pylori infection has been implicated in acute gastritis, chronic atrophic gastritis, peptic ulcers as well as gastric cancer. Since we have documented that anti-H. pylori, anti-inflammatory, anti-oxidative, and anti-mutagenic actions of Korean red ginseng and the enhancing anti-inflammatory activities and attenuating anti-inflammatory roles of Lactobacillus plantarum, in the current study, we investigated the effects of L. plantarum-fermented Korean red ginseng on subacute or chronic pathology in H. pylori-infected mouse model. 5-week-old interleukin-10 deficient mice were inoculated with H. pylori (Sidney strain 1), after which L. plantarum (Lp), Korean red ginseng (RG) and fermented Korean red ginseng (FRG) were administrated by drinking water for 14 or 24 weeks. After killing, in addition to gross and pathologic evaluations, the expressions of inflammatory enzymes or cytokines were analyzed by Western blot analysis or ELISA, respectively. H. pylori infection induced the expression of inflammatory enzymes, iNOS and COX-2, and cytokines such as IL-1β and IL-6 in subacute 14 weeks model. Moreover, H. pylori infection significantly provoked tumorigenesis in chronic 24 weeks model. Lp, RG and FRG inhibited the expression of inflammatory enzymes and cytokines in both subacute and chronic models. Among those, FRG showed the significant anti-inflammatory and anti-tumorigenic effects on H. pylori-infected gastric carcinogenesis reflected with decreased incidence of tumor formations. Probiotics fermented Korean red ginseng exerted significant protections against H. pylori infection through attenuating gastritis, rescuing from tumorigenesis and enhancing gastroprotection. We suppose that chronic intake of FRG can be an anticipating strategy in chemoprevention of H. pylori-associated gastric cancer.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B45.
Abstract B52: The role of p38 activation in nucleotide excision repair in human skin
Authors: Christian Perry , D'Orazio John
Published: June 2012

Keratinocyte-based skin malignancies are diagnosed over one million times a year in this country alone despite widespread knowledge about UV avoidance and sunscreen use. The majority bear evidence of UV-induced mutations in key cancer-related genes such as TP53, highlighting the importance of environmental sun and tanning bed exposure in their pathophysiology. Accumulation of UV-induced DNA mutations, and ultimately skin cancer risk, is determined not only by UV exposure but also by the ability of keratinocytes to repair mutagenic damage caused by UV radiation. Xeroderma pigmentosum patients, in whom DNA repair is defective due to homozygous loss of any one of at least eight enzymes in the nucleotide excision repair (NER) pathway, suffer exceptionally high incidences of UV-induced skin cancers, illustrating the importance of NER in resistance to skin cancer. There is little understanding of the factors that determine the efficiency of NER in the skin. We have found that NER can be modified exogenously by inducing a cAMP-based pathway in the skin. Specifically, topically-applied forskolin, an activator of adenylate cyclase reproducibly enhances clearance of UV-induced cyclobutane dimers in human skin explants and in human keratinocytes. Pharmacologic induction of cAMP via forskolin efficiently activates the protein kinase A (PKA) signaling cascade and leads to downstream phosphorylation of the cAMP responsive binding element (CREB) transcription factor. Intriguingly, we and others have found that UV radiation also results in robust CREB phosphorylation in human skin and human keratinocytes, but in a PKA-independent manner. Furthermore, UVB induced CREB phosphorylation displays similar kinetics to UVB induced p38 activation and is diminished upon p38 inhibition. Together, these data suggests the p38 damage response pathway, recruited by UV, directly phosphorylates CREB without involving the cAMP second messenger. Currently, we are determining the effects of p38 inhibition on NER activity. We hypothesize that inhibiting p38 will lead to decreased NER activity in human skin and this loss of NER can be overcome with the addition of forskolin. Our observations presented here suggest that the p38/CREB signaling axis may be a major determinant of NER efficiency in the skin and raise the exciting possibility of a novel skin cancer preventative approach outside of UV-avoidance.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B52.
Abstract B86: Indoor tanning use and incidence of skin cancer
Authors: Zhang Mingfeng , Qureshi Abrar A. , Geller Alan , Frazier Lindsay , Hunter David , Han Jiali
Published: June 2012

Tanning beds are used by 30 million Americans each year. The use of tanning beds has been shown to increase the risk of skin cancers in previous epidemiological studies. A 2007 meta-analysis by the International Agency for Research on Cancer (IARC) reported positive associations of ever-use of tanning beds with increased risks of melanoma and squamous cell carcinoma (SCC). In 2009, the IARC classified UV radiation from tanning beds as human carcinogen (group 1). However, risk effect of indoor tanning on basal cell carcinoma (BCC), the most prevalent skin cancer in Caucasians, has been inconclusive. Besides, evidence for a dose-response relationship with melanoma and SCC was inconsistent across previous studies. In this study, using a large and well-characterized cohort in the U.S., the Nurses' Health Study II, we followed up 73,494 female nurses for 20 years and investigated the frequency of tanning bed use during high school/college, at age 25–35, as well as the overall average usage during both periods in relation to three types of skin cancer (BCC, melanoma, and SCC). We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for each type of skin cancer. During follow-up, 5,526 BCC cases, 348 melanoma cases, and 400 SCC cases developed. We found highly significantly elevated risk of BCC among participants who used tanning beds either during high school/college or at ages 25–35 (p < 0.001). The multivariable-adjusted HR for 1 time/year use was 1.10 (95% CI 1.08–1.12) with the use during high school/college and 1.06 (95% CI 1.04–1.07) with the use at ages 25–35. A dose-response effect was detected for all three types of skin cancers, with the multivariable-adjusted HRs for average 1 time/year use during both periods of 1.04 (95% CI, 1.03–1.05; p < 0.001) for BCC, 1.03 (95% CI, 0.995 − 1.06; p = 0.09) for melanoma, and 1.05 (95% CI, 1.02–1.08; p = 0.002) for SCC. Compared to individuals who used tanning beds from ages 25–35, we found a significantly higher risk of BCC for those who used it during high school/college (p for heterogeneity = 0.002). Of note, for those with > 6 times/year use, the multivariable-adjusted HR of BCC compared to non-users was 1.35 (95% CI, 1.23–1.49) at ages 25–35 and 1.82 (95% CI, 1.60–2.08) during high school/college (p for heterogeneity < 0.001). Our data provide strong evidence for an association between tanning bed use and the risk of skin cancers with a dose-response effect, especially for BCC.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B86.
Abstract B88: Comorbidity and survival among black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer
Authors: Lu Yani , Ma Huiyan , Sullivan-Halley Jane , Malone Kathleen E.
Published: June 2012

Introduction: The impact of comorbidity on overall survival among older women diagnosed with breast cancer has been studied extensively. However, less is known about its impact on overall survival among women diagnosed with breast cancer before age 65 years.

Methods: We followed 4516 (1605 black, 2911 white) women ages 35 to 64 years when diagnosed with incident invasive breast cancer between 1994 and 1998. The pre-diagnosis history of 11 comorbid conditions and whether they had been treated were collected shortly after breast cancer diagnosis. Multivariate Cox regression models were used to examine the impact of these comorbidities on overall survival.

Results: During a median of 8.2 years follow-up, 1052 (524 black, 528 white) women died. The prevalence of comorbidities diagnosed before breast cancer was higher among black women than among white women (61.3% vs. 44.7%). Compared to women without any comorbidities, women were at increased risk of death if they had any treated comorbidity except when gallbladder disease; peptic, stomach, gastric, or duodenal ulcer; or liver disease was the only comorbidity. The risk of death increased with increasing number of treated comorbidities (P-trend<0.001; adjusted relative risk [RR] of death=1.21, 1.20 and 1.90 for women with 1, 2, and 3 or more comorbid conditions). However, when stratified by tumor stage, having more comorbid conditions was associated increasing mortality risk among women diagnosed with localized tumors (P-trend<0.001), but not among women diagnosed with non-localized tumors (P-trend=0.29) (P for homogeneity of trend<0.001). This risk pattern was consistent among black women and white women.

Conclusions: Among women ages 35 to 64 years when diagnosed with invasive breast cancer, having more comorbidities at breast cancer diagnosis has a greater impact on overall survival for women with localized tumors than for women with non-localized tumors.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B88.
Abstract B90: Diabetes and the risk of colorectal adenomas: Black Women's Health Study
Authors: Dash Chiranjeev , Palmer Julie R. , Rosenberg Lynn , Boggs Deborah A. , Adams-Campbell Lucile L.
Published: June 2012

Introduction: Metabolic abnormalities associated with diabetes mellitus (DM) are hypothesized as colorectal carcinogenesis mediators. Results from epidemiologic studies on the association of DM with colorectal cancer are inconclusive. However, limited data from small case-control studies suggests a stronger association of diabetes with colorectal adenoma. Given the relative lack of information on the risk of colorectal adenomas in African-American women, and the higher prevalence of diabetes in African Americans we investigated DM as a risk factor for colorectal adenomas in the Black Women's Health Study.

Methods: We conducted a nested case-control study among participants in the Black Women's Health Study - a cohort study of 59,000 women followed biennially since 1995. Cases were defined as women diagnosed with incident colorectal adenoma between 1997 and 2009. Only those adenoma cases verified by medical record review were included. Controls were participants who also underwent lower gastrointestinal endoscopy in the same period and in whom no adenoma or other polyp was found. DM and insulin use were self-reported by participants on each biennial questionnaire. Using logistic regression models, we obtained odds ratios (OR) for colorectal adenoma in relation to DM, adjusting for age, education, body mass index, physical activity, fruit and vegetable intake, family history of colorectal cancer, smoking, alcohol intake, energy intake, and aspirin use.

Results: There were 742 adenoma cases and 14,434 non-cases. After adjusting for multiple covariates, there was no association of DM with colorectal adenomas (OR: 1.02, 95% CI: 0.82–1.26) in this study of African-American women. Insulin therapy for DM was also not associated with adenoma risk. Compared to women without DM, the ORs (95% CI) for diabetic women using insulin, and those not using insulin were 1.14 (0.78–1.68) and 0.98 (0.78 − 1.25), respectively.

Conclusions: We did not find an association of DM with colorectal adenomas among African-American women. Our results support the findings from two recent cohort studies that showed no association of type 2 DM with colorectal cancer in women. Further research is needed to confirm these findings in African American women, and explore the association of DM and colorectal adenoma in African-American men.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):B90.
Abstract CN02-02: Ovarian cancer GWAS: Path from risk assessment to prevention?
Authors: Sellers Thomas A.
Published: June 2012

Ovarian cancer risk is known to be influenced by highly penetrant mutations in BRCA1 and BRCA2. However, these are rare in the population and collectively account for around 10% of cases. Since these genes account for less than 50% of the familial risk of ovarian cancer, other loci must surely exist. Genome wide association studies have contributed to the identification of at least six additional chromosomal regions harboring common genetic variants that are associated with modest levels of risk increase or decrease. The knowledge of Mendelian and oligogenic susceptibility genes lays the foundation for risk-appropriate preventive interventions. Several options have already been identified through epidemiologic research, ranging from relatively innocuous strategies such as use of oral contraceptives, to more invasive surgical approaches such as tubal ligation and oophorectomy, each with varying degrees of effectiveness as well as complication rates and side effects. The level of genetic risk should inform decisions and strategies as to the appropriate intervention. However, there is a need for less invasive prevention strategies, especially chemoprevention. Finally, more progress is needed in the translation and dissemination of risk assessment to risk reduction in the clinical practice and public health settings.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN02-02.
Abstract CN02-03: Prevention of human papillomavirus-related malignancy in the post-vaccine era
Authors: Goodman Marc T.
Published: June 2012

We are presently at a crossroads in clinical practice as new public health models for cervical cancer prevention and detection are being developed and tested. In the US, we are in the midst of redefining government policy and medical decision-making based on human papillomavirus (HPV) natural history studies, randomized trials, and prophylactic vaccine uptake. Novel diagnostic, progression and treatment approaches are emerging that are based on a paradigm that recognizes the central role of HPV persistence in anogenital cancer development. Gaps in epidemiological and clinical research will be examined including the role of immune markers in viral clearance, the transmission dynamics of anogenital HPV infection, novel screening modalities in high risk populations, and the implementation of population-based surveillance activities to determine the public health benefit and cost-effectiveness of the prophylactic HPV vaccine.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN02-03.
Abstract CN04-01: New drugs for the chemoprevention of experimental breast cancer
Authors: Liby Karen T. , Tran Kim , Kim Eun-Hee
Published: June 2012

Tamoxifen, raloxifene and exemestane are all effective for prevention of estrogen-receptor positive (ER+) breast cancer in women. Despite these significant advances, novel drugs are needed for the chemoprevention of estrogen-receptor negative (ER−) breast cancer, especially for women with hereditary breast cancers who frequently harbor BRCA (breast cancer-associated gene) mutations. Currently, “watchful waiting” or bilateral prophylactic mastectomy is offered to these patients, although these high risk women are ideal candidates for an effective, safe chemopreventive regimen. Two relevant mouse models were used to study drugs that are used to treat human breast cancer or drugs with known chemopreventive activity in other animal models. When conditional knockout (co) of BRCA1 is coupled with a mutation in p53, Brca1Co/Co;MMTV-Cre;p53+/− mice develop ER− mammary tumors within 6–10 months of age. In the PyMT mouse model, the polyomamiddle T oncoprotein drives carcinogenesis by inducing significant infiltration of tumor-associated macrophages (TAM). The efficacy of synthetic triterpenoids, rexinoids, histone deacetylase inhibitors, and PARP (Poly ADP ribose polymerase) inhibitors as well as potential biomarkers and mechanisms for these drugs will be discussed.

Supported by the Breast Cancer Research Foundation and Komen for the Cure

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN04-01.
Abstract CN04-02: Tumor and genomic heterogeneity in breast cancer prevention
Authors: Ambrosone Christine B.
Published: June 2012

Prevention of breast cancer, first and foremost, requires an understanding of the etiology of the disease. Although epidemiological studies have identified a number of risk factors for breast cancer over the last several decades, there is still a sizeable proportion of variability in disease incidence that is unexplained. It is likely that heterogeneity, both in tumor biology and in inherent genomic make up, may blur potential associations. If we accept that breast cancer is more than one disease, as increasingly demonstrated by better understanding of breast tumor subtypes, then it stands to reason that risk factors may differ in etiologic pathways. For example, parity has long been considered to reduce risk of breast cancer. However, there is a growing body of evidence suggesting that having children does reduce risk of estrogen receptor (ER) positive or luminal A breast cancer, but actually increases risk of ER negative and/or basal-like breast cancer, which occurs more often in women of African ancestry. Further examination of risk factors by breast cancer subtypes may clarify some of the uncertainty regarding associations between other exposures and breast cancer risk.

In addition to tumor heterogeneity, the genetic make-up of at-risk populations is known to vary substantially. Common differences in genomic DNA, such as single nucleotide polymorphisms (SNPs), occur in genes that are involved in numerous pathways that could be related to breast cancer risk, including hormone metabolism, carcinogen activation and detoxification, DNA repair, and cell cycle control. Although there has been focused attention on the potential role of gene/environment interactions in breast cancer risk over the last decades, with some persuasive findings, the majority of these studies have not examined such associations in relation to breast tumor subtypes. In this presentation, the role of tumor and genomic heterogeneity in breast cancer risk will be presented, particularly in relation to breast cancer in African American women, and potential preventive strategies will be discussed.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN04-02.
Abstract CN05-01: An overview of biomarker discovery and development
Authors: Srivastava Sudhir
Published: June 2012

Two great challenges in cancer diagnosis and prevention are 1) the detection of specific preinvasive neoplastic lesions that give origin to malignant tumors and 2) the identification of those markers that predict the outcome of individual cancer patients. Neoplastic lesions may derive from epithelial or nonepithelial cellular populations. Often, preinvasive neoplastic lesions are small, multiple and may display wide ranges of diversity. Morphological alterations characterizing preinvasive neoplastic lesions include nuclear pleomorphism consisting of increased variation in nuclear size, shape, and hyperchromatism, abnormal mitoses, abnormal nucleolar patterns and altered or absent differentiation. The evolution of these types of lesions may take three directions: spontaneous regression, progression toward a fully malignant phenotype, or stasis, remaining as a preinvasive neoplastic lesion. Although there are discrepancies in terminology used by pathologists to describe these types of early neoplastic lesions, they are most frequently referred to as preinvasive neoplasia, dysplasia, carcinoma in situ, intraepithelial neoplasia, or as incipient cancer.

Carcinogenesis is an indivisible continuum of molecular and morphological changes that may culminate in the development of invasive tumors. Studies in which the molecular features of preinvasive neoplastic lesions are correlated with molecular features of matching invasive lesions, for example, a colorectal cancer with an adenomatous polyp forming its edge, should be useful in identifying molecular features associated with greater risks of progression. Similarly, studies of prognostic factors in specific cancers may identify molecular features associated with aggressive behavior.

In this session we will discuss the molecular aspects of early preinvasive neoplastic lesions; specifically, alterations in genes regulating proliferation, differentiation, apoptosis and invasiveness as well as chromosomal aberrations and microsatellite instability will be addressed. We will argue that the identification of molecular changes associated with neoplastic transformation will lead to the development of new molecular markers for the early detection of preinvasive neoplastic and malignant lesions, assessment of cancer risk, assessment of responses to preventive or therapeutic interventions, and separation of less aggressive neoplastic lesions from more aggressive lesions.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN05-01.
Abstract CN06-01: Phase IIa trial of sulindac in individuals at increased risk for melanoma
Authors: Curiel-Lewandrowski Clara , Alberts D.S. , Chow H-H.S. , Swetter S. , Einsphar J. , Hsu C.-H. , Hsu C.-H. , Nagle R. , Sagerman P. , Tangrea J. , Parnes H.
Published: June 2012

Some epidemiological studies and several experimental publications suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of melanoma. However, specific information on the ability of NSAIDs to reach melanocytes in vivo and to modulate key biomarkers in pre-neoplastic lesions such as dysplastic nevi have not been evaluated to date. Methods: We conducted a randomized, double-blind, placebo controlled trial of sulindac in individuals at risk for melanoma to determine whether sulindac and related metabolites are bioavailable in the nevi and whether sulindac intervention has an effect on apoptosis and vascular endothelial growth factor (VEGF) expression in atypical nevi (AN). Fifty healthy subjects with ≥ 4 large (≥5 mm and < 15 mm) AN and one benign nevus (BN) were enrolled between 2/09 and 7/10. Subjects underwent clinical and dermoscopic evaluation of their melanocytic lesions with 2 AN randomized to be excised at baseline for biomarker evaluation and 2 AN to post-intervention evaluation. Subsequently, participants were randomized to receive sulindac (150 mg BID) or placebo for 8 weeks. Upon completion of the intervention the residual 2 AN and the BN were surgically removed. Results: The study intervention was well tolerated with some mild or moderate gastrointestinal adverse events that were possibly or probably related to the intervention. Sulindac, sulindac sulfone, sulindac sulfide concentrations were 0.31 ± 0.36, 1.56 ± 1.35, 2.25 ± 2.24 μg/ml, respectively, in post-intervention plasma samples from the sulindac group. Sulindac, sulindac sulfone, sulindac sulfide concentrations were 0.51 ± 1.05, 1.38 ± 2.86, 0.12 ± 0.12 μg/g tissue, respectively, in post-intervention nevi samples. Eight weeks of sulindac intervention did not result in significant changes in VEGF expression. Sulindac intervention increased the expression of a marker of apoptosis, cleaved caspase 3 (an increase of 3 ± 33 in the sulindac arm vs. a decrease of 25 ± 45 in the placebo arm, p = 0.0056) in dysplastic nevi. After adjusting for baseline expression, the significance of this finding is attenuated to a p-value of 0.1103 based on a linear regression model. Overall, these findings are consistent with the identification of high concentrations of sulindac sulfone, a pro-apoptotic metabolite in the nevi. Conclusion: The study showed that sulindac and sulindac metabolites can reach measurable levels in melanocytic nevi. Eight weeks of sulindac intervention induced the expression of a marker of apoptosis in dysplastic nevi but did not result in significant changes in VEGF expression. The study findings support the further evaluation of sulindac as a chemopreventive agent for melanoma.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN06-01.
Abstract CN07-02: Molecularly targeted cancer prevention: From discovery to medicine
Authors: Dong Zigang
Published: June 2012

Despite the intensive efforts and substantial advances that have occurred through focusing on improving treatment, cancer is still a leading cause of death worldwide. Many have argued that this could be avoided by focusing on cancer prevention, which has now entered the arena of targeted therapies. During the process of identifying preventive agents, dietary phytochemicals have emerged as modulators of key cellular pathways. By molecular modeling of the interactions of targeted proteins with these chemopreventive agents, we have provided knowledge for a better understanding of how these preventive agents work. Such knowledge will help the translation to new clinical practice of preventive medicine.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN07-02.
Abstract ED02-02: Second cancers among cancer survivors: High-risk populations to target for prevention
Authors: Oeffinger Kevin C.
Published: June 2012

There are now over 12 million cancer survivors in the United States. Given advances in early detection, supportive care, and therapy, the 5-year overall survival rate for all invasive cancer types exceeds 67%. For many common cancers, such as breast, prostate, testicular, thyroid, bladder, and endometrial cancer, melanoma, and Hodgkin lymphoma, the overall 5-year survival rate exceeds 80%. As the number of long-term survivors has increased, there has been a growing awareness that many will develop health conditions as a direct or an indirect consequence of their cancer therapy or lifestyle, environmental and genetic factors associated with the primary cancer. One of the most serious outcomes experienced by cancer survivors is the diagnosis of a second cancer. The number of patients with multiple primary cancers is growing, with independent malignancies comprising about 16%. Second cancers are a major contributing factor to late mortality following the primary cancer for several high risk groups, including survivors of pediatric or young adult Hodgkin lymphoma. This presentation will describe the current estimates for second cancers, identify high risk populations, and discuss long-term screening strategies and risk-reducing interventions.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED02-02.
Abstract ED03-02: Issues in applications of genome-wide methylation data to epidemiology
Authors: Kelsey Karl T.
Published: June 2012

Epigenetic alterations are now well accepted as crucial changes in the development of cancer. Common epigenetic mechanisms affecting carcinogenesis ultimately phenotypically affect gene expression and genomic stability. This is effected through altered miRNAs, dysregulation of the histone code, changes in the chromatin structure and common changes in DNA methylation, again most commonly occurring at CpG dinucleotides, in specific gene regions and at well known DNA repeat regions. There is limited knowledge of the environmental or physiological factors that are associated with most of these somatic changes and epidemiologic investigation is poised to provide significant important information in human studies. In this presentation we will assess the types of epigenetic alterations amenable to epidemiologic investigation and discuss applications and interpretations of the data, including contrasting phenotypically driven candidate and discovery-based approaches, identifying appropriate cell types for different study designs and briefly touching upon the opportunities and limitations of various approaches.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED03-02.
Abstract ED04-03: Aspirin chemoprevention for Barrett's and esophageal cancer: The AspECT trial
Authors: Jankowski Janusz A.
Published: June 2012

Esophageal adenocarcinoma is increasing in the world. The premalignant lesion Barrett's esophagus is also being rapidly recognized. Unfortunately cost effective analyses has shown that the best strategy for prevention is chemoprevention of the premalignant lesion. Of the agents available for chemoprevention aspirin has arguably the best evidence. The efficacy of aspirin cancer prevention is probably now known and rests between 20–30% of the population. The big issues which remain are A. What is the percentage of serious side effects in aspirin takers? B. does concomitant medication abrogate or accentuate the risk benefit ratio? C. What biomarkers or genetic factors predict an optimal risk benefit ratio? The ASPirin Esomeprazole Chemoprevention Trial (ASPECT) is specifically designed to address these issues in patients with Barrett's esophagus.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED04-03.
Abstract ED05-01: Social media and cancer communications: Promises and perils
Authors: Viswanath K. Vish
Published: June 2012

The emergence of social media as a platform to communicate, network and mobilize is receiving considerable attention in mainstream media. For example, the use of social media has received both credit for the changes in the Middle East and blame for the recent riots in the United Kingdom. The potential to reach a networked and engaged “audience” in hundreds of millions offers significant promise to those in cancer communications to communicate risk and influence behaviors. Despite the promise, significant challenges need to be addressed to exploit the potential of the platform. These challenges include (a) varying characteristics of different social media platforms; (b) characterizing the nature of engagement and the interest of social media users, (c) multiple contesting interpretations of risk among message sponsors, (d) persistent problem of digital divide that social media could potentially bridge or exacerbate, and (e) measurement challenges including difficulty in assessing their impact. The overview will cover these challenges followed by speakers addressing specific cancer-related risk communication issues including tobacco use, communication inequalities and exemplar interventions that address different health risks.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED05-01.
Abstract ED05-03: Social media use, communication inequalities, and public health: Where we are and where we need to go
Authors: Kontos Emily Z.
Published: June 2012

Social media are emerging as an important platform for communication and health information exchange. Yet, despite the increase in popularity and use, only a limited number of empirical studies document which segments of the adult population are and are not using social media and with what, if any, affect on health. Preliminary studies highlight that while there are still significant inequalities by race and socioeconomic status in Internet access, once access is gained, use of social media such as social networking sites is equally prolific across socio-demographic groups. This ubiquity of use presents both significant opportunities and challenges for cancer communication efforts. With the new communication channel emerges a real need for refined measurement that adequately reflects the innate dynamism of the platform and a nuanced understanding of the links between computer/technology-mediated communication and health across populations to ensure that existing digital divides and health disparities are not exacerbated but rather narrowed.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):ED05-03.
Abstract PL01-02: Building the Texas Cancer Diagnostics Pipeline one biomarker at a time
Authors: McDevitt John T.
Published: June 2012

Diagnostic tools have not kept pace with medical knowledge. Fields of proteomics, genomics, and bioinformatics have enjoyed explosive growth, but precious few biomarkers found are translated into clinical practice. More than 20,000 scientific-discovery papers for cancer and 6,000 for cardiac disease have been published, yet only about one biomarker per year for ALL diagnostics areas received FDA each year. Unless biomarkers receive FDA approval they cannot move into widespread clinical practice in the US. Rich biomarker data combined with microfabrication techniques can provide means to deploy quick, affordable point-of-care diagnostics. This newfound wealth of information has strong potential to be used to build a “biomarker highway” and develop low-cost, advanced diagnostic tools that identify diseases early including various types of cancers, when they are less costly. This presentation features creation of programmable nano-bio-chip sensors that are capable of sophisticated measurements of strategic biomarkers from bio-fluid samples like blood, urine and saliva. This universal detection modality is now of a fast track to FDA approval through the simultaneous completion of 6 clinical trials in the area of HIV immune function (number one global humanitarian issue), cardiac heart disease (largest killer globally) and three types of cancers (oral, ovarian, prostate). These powerful devices have secured Popular Science Best of What's New (medical device category) as well as Science Coallition's Discovery of Year. The talk will highlight activities related to the recent launching of the Texas Cancer Diagnostics Pipeline.

Short Description: Programmable bio-nano-chip sensors are now in development with goal to diagnose cancer early while at the same time making healthcare more affordable and accessible globally.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL01-02.
Abstract PL04-01: Early Detection Research Network: Biomarker discovery and validation - A team approach
Authors: Thompson Ian M.
Published: June 2012

While the principle of early detection and treatment of cancer through the use of diagnostic tests including biomarkers may seem to be a straightforward process, the rate of registration of new cancer-related biomarkers (approximately one per year) illustrates the substantial challenges to this science. Essential elements of a successful biomarker include sensitivity in the face of cancer, specificity in the cancer-free state as well as in the face of disease which may clinically mimic cancer or which is associated with a higher cancer risk, a reproducible, accurate, and portable assay, and, more recently, evidence that the specifics of the cancer detected (stage and prognosis, for example) leads to reductions in morbidity, mortality, or, possibly, cost. There is possibly no greater opportunity for team science to merge discovery, validation, and clinical efficacy than in cancer biomarkers. The EDRN, now 11 years old, envisioned such a collaboration, including Biomarker Development Laboratories, Biomarker Reference Laboratories, Clinical Validation Centers, an Informatics Center, and a Data Management and Coordinating Center. EDRN member institutions participate in organ working groups including Breast and Ovarian, GI, Prostate and GU, and Lung. Organ working groups function as teams, all focused on collaborative science with the ultimate goal of validation of biomarkers for the purpose of improvements in clinical care. Cross-organ-site team collaborations also occur as biomarkers or concepts that are applicable to multiple organ sites are evaluated. Teams include biostatistical expertise that has developed new methods for biomarker evaluation and validation. Finally, the EDRN is an open organization that seeks to partner with non-EDRN investigators through sharing of biospecimens, clinical data, and new analysis techniques to further the goal of early cancer detection.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PL04-01.
Abstract PR-01: Properties of adenomas in subjects treated with difluoromethylornithine and sulindac for reduction of colorectal adenomas
Authors: Carpenter Philip M. , Chen Wen-Pin , McLaren Christine E. , Gerner Eugene W. , Meyskens Frank L.
Published: June 2012

Difluoromethyl ornithine (DFMO), an ornithine decarboxylase inhibitor, and sulindac reduced the occurrence of colorectal adenomas by 70% in a phase III randomized placebo controlled clinical trial. The goal of the current study was to compare adenoma location in the colorectum and biomarker expression by immunohistochemistry of formalin fixed paraffin embedded adenomas from treatment and placebo groups in the trial. To take into account the relationship between the locations in the colorectum of multiple adenoma that were removed from individual subjects, the generalized estimation equation (GEE) method was applied for all analyses. The decrease in the reappearance of metachronous adenomas was similar throughout the colorectum in subjects treated with DFMO and sulindac (P = 0.44). For TP53, Ki67, and c-MYC there were no significant differences in the estimated mean percent of cells staining positive between treated and untreated subjects (P>0.5 for all). For BCL-2, LC3B, CEA, sialy1-Tn, cleaved caspase 3 and apoptosis, the proportion of adenoma with expression levels 1+ to 3+ did not differ between subjects treated with DFMO plus sulindac versus those treated with double placebos. For hMSH2, hMSH6, hMLH1 and hPMS2, there was a loss of staining of a greater number of cells on average in adenomas from the control group compared to adenomas from the subjects treated with DFMO and sulindac. For hMSH2, this difference was statistically significant (P = 0.0004). This finding raises the possibility that DFMO and sulindac protect adenomas from loss of DNA mismatch repair protein expression and provides a rationale for further study of the possible role of DFMO and sulindac on DNA mismatch repair protein regulation and chemoprevention in patients at risk for colorectal carcinoma. In conclusion, DFMO decreases the occurrences of adenomas throughout the colorectum, including the right colon, and may have an effect on DNA mismatch repair enzyme expression. These findings provide further rationale for the use of DFMO as a chemopreventative agent for colorectal carcinoma.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PR-01.
Abstract PR-02: The association between antioxidant intake and ovarian cancer risk: Results from a population-based case-control study in New Jersey
Authors: Gifkins Dina , Olson Sara , Paddock Lisa , King Melony , Demissie Kitaw , Lu Shou-En , Bandera Elisa
Published: June 2012

Ovarian cancer causes significant morbidity and is associated with the highest mortality among gynecologic cancers. Etiologic theories of ovarian cancer indicate that oxidative stress may have a role its development. It has been suggested that limiting oxidative stress to the ovarian epithelium could be considered a first-line defense against ovarian cancer. Although evidence for an association between individual dietary antioxidant intake and ovarian cancer risk is conflicting, the combined evidence suggests a modest inverse association with intake.

We evaluated the role of total dietary antioxidant capacity and intake of individual antioxidants (vitamin C, vitamin E, beta-carotene, selenium, lutein, and lycopene) on ovarian cancer risk in a population-based case-control study in New Jersey. Cases included women ages 21 years and older with newly diagnosed epithelial ovarian cancer who resided in six counties of New Jersey. Controls were women in the same age range who resided in the same geographic area. Women with a hysterectomy or bilateral oophorectomy were excluded. Dietary intake was assessed using the Block food frequency questionnaire (FFQ), and total antioxidant indices were constructed by linking FFQ-derived estimates to two standardized antioxidant capacity databases, the USDA Oxygen Radical Absorbance Capacity (ORAC) Database, and the University of Olso's Antioxidant Food Database. Multivariate logistic regression models were used to calculate odds ratios and 95% confidence intervals while controlling for major ovarian cancer risk factors.

Total antioxidant intake was not found to be associated with ovarian cancer risk. However, a strong protective effect was observed for the highest tertile of dietary selenium intake compared to the lowest (OR: 0.41; 95%CI: 0.20–0.85). In contrast, supplement use was associated with significant increased risks for all micronutrients. Vitamin C supplement use was associated with an increased risk of 1.63 (95%CI: 1.01–2.62), with similar results for vitamin E supplement use (OR: 1.63; 95%CI: 1.02–2.63), beta-carotene supplement use (OR: 1.69; 95%CI: 1.08–2.66) and selenium supplement use (OR: 1.64; 95%CI: 1.05–2.56).

In conclusion, we observed a strong decreased risk for ovarian cancer with dietary selenium intake. No associations were observed with total antioxidant intake or any other antioxidant micronutrients, while increased risks were observed with antioxidant supplement intake. Additional research is needed to confirm these findings.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PR-02.
Abstract PR-07: Stress management improves prevention relevant outcomes among women at risk for breast cancer
Authors: McGregor Bonnie A. , Albano Denise L. , Dolan Emily D. , Ceballos Rachel M.
Published: June 2012

Many psychosocial intervention studies have focused on treating cancer survivors, but less attention has been focused on those at risk for cancer. Women with a family history of breast cancer can't control their familial risk for cancer, but there are a number of risk-related factors they can control. These include immune function, body weight, diet, and physical activity. Psychological distress modulates all of these. If psychological distress is associated with poor immune function, poor diet, decreased physical activity, and increased BMI, reducing psychological distress should be associated with improved immune function, improved diet, increased physical activity, and lower BMI. We randomized 104 women (mean age 43 (SD=10.7), 87% white, mean education 17 years (SD 2.3)) with a family history of breast cancer who were also reporting elevated levels of distress to receive a cognitive behavioral stress management (CBSM) intervention or wait list control. CBSM women reported decreased distress, improved antibody response to Hepatitis A vaccine, decreased fat consumption, increased fiber consumption, increased leisure time physical activity, and a slight decrease in BMI over the 7 month course of the study that was significant when compared to the increased BMI among the waitlist control group women (all p's<.05). Cognitive behavioral stress management modulates outcomes important for cancer risk reduction among stressed women at increased risk for breast cancer due to family history. Cognitive behavioral stress management should be considered when counseling high risk women about managing their breast cancer risk.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):PR-07.