bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A59: Selenoprotein gene variants and risk of esophageal and gastric cancer in a Chinese population
Authors: Lin Shih-Wen , Freedman Neal D. , Taylor Philip R. , Qiao You-Lin , Abnet Christian C. , Hyland Paula , Hu Nan , Fan Jin-Hu , Yu Kai , Dawsey Sanford M. , Wheeler Bill , Ding Ti , Tang Ze-Zheng 
Published: June 2012

Abstract
Objectives: Observational studies and intervention trials suggest that selenium has potential cancer prevention properties. We previously found that selenium supplementation reduces cancer mortality, particularly gastric cancer mortality, in a high-risk region in China, and that low serum selenium concentration is associated with increased risks of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). In humans, selenium may exert chemopreventive actions through the 25 known selenoproteins, which contain residues of selenocysteine, the 21st amino acid. Therefore, genetic variants in selenoprotein genes may influence susceptibility to ESCC and GCA, yet no previous studies have comprehensively investigated these potential associations. Thus, we examined the association between genetic variants in selenoprotein and selenium metabolism genes and risks of ESCC and GCA.
Methods: We included 1027 ESCC and 753 GCA cases plus 1452 controls from two epidemiologic studies in the high-risk region in China. We genotyped 272 tag single nucleotide polymorphisms (SNPs) in all 25 known selenoprotein genes and 4 selenium metabolism genes. For each gene, we calculated a standardized summary p-value using the adaptive rank truncated product (ARTP) method. For SNPs, logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).
Results: In gene-based tests, the selenoprotein gene SELS (selenoprotein S) was associated with ESCC risk (p=0.00070); TXNRD2 (thioredoxin reductase 2) showed borderline non-significant associations with both ESCC (p=0.063) and GCA (p=0.051). In SNP-based tests for these two genes, rs8029790 (tagged to SELS in the upstream noncoding region) was associated with a 1.30-fold increased risk of ESCC (CI=1.14, 1.47; p=0.000052), whereas rs2073750 (tagged to intron in TXNRD2) was associated with risks of both ESCC (OR=0.84, CI=0.74, 0.94; p=0.0029) and GCA (OR=0.82, CI=0.72, 0.93; p=0.0026).
Conclusions: The potential anticarcinogenic properties of selenium may be due to its presence as the amino acid selenocysteine in human selenoproteins. The association of SNPs in selenoprotein genes SELS and TXNRD2 with ESCC and GCA risk suggests that selenium and these selenoproteins may play an important role in cancer development. Our findings warrant further research on elucidating the functional effects of these SNPs on selenoproteins in the context of upper gastrointestinal (UGI) carcinogenesis so that we can better understand the role of selenium supplementation in cancer prevention.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A59.
Abstract A60: Vitamin D related genetic variation, plasma vitamin D, and risk of lethal prostate cancer
Authors: Shui Irene M. , Stampfer Meir J. , Giovannucci Edward , Mucci Lorelei A. , Kraft Peter , Lindstrom Sara , Penney Kathryn , Nimptsch Katharina , Hollis Bruce W. , Tamimi Rulla M. , Platz Elizabeth 
Published: June 2012

Abstract
Background: The association of vitamin D status with prostate cancer is controversial, with no association observed for overall incidence, but a potential link with lethal disease.
Methods: We assessed prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and variation in vitamin D related genes and the risk of lethal prostate cancer using a prospective case-control study nested within the Health Professionals Follow-up Study. We included 1328 incident cases diagnosed following blood draw (1993–95) and 1331 controls. Men with prostate cancer were followed through March 2011 for lethal outcomes (n=111). We selected 97 linkage disequilibrium tagSNPs to represent common genetic variation across seven vitamin D related genes (CYP27A1, CYP2R1, CYP27B1, GC, CYP24A1, RXRA, VDR). We used a logistic kernel machine test to assess the multimarker pathway global association for ‘SNP-sets’ defined by the seven genes with prostate cancer.
Results: Higher levels of 25(OH)D were associated with about half the risk of lethal prostate cancer (OR comparing extreme quartiles: 0.45; 95% CI:0.25–0.81). This finding did not vary by time from blood draw to diagnosis. We found no significant association of 25(OH)D with overall prostate cancer risk(OR comparing extreme quartiles: 1.05; 95% CI: 0.85–1.30). The total vitamin D pathway SNP-set (seven genes) as well as SNP-sets defined by the individual genes (VDR, RXRA, or CYP27A1) were nominally associated with lethal prostate cancer risk (p&lt;0.05), but not overall prostate cancer (p=0.41). Conclusions: In this large prospective study, plasma 25(OH)D and common variation across vitamin D pathway genes were associated with lethal prostate cancer risk. Studies of vitamin D and prostate cancer should focus on lethal disease.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A60.
Abstract A65: Does the lifetime number of ovulatory cycles predict the risk of breast cancer in BRCA1 and BRCA2 mutation carriers?
Authors: Kotsopoulos Joanne , Sun Ping , Narod Steven 
Published: June 2012

Abstract
Background: In the general population, various reproductive factors are believed to influence breast cancer risk via their effects on the number of ovulatory cycles and subsequently on cumulative endogenous hormonal exposure. It is not clear to what extent this is true for women with a BRCA1 or BRCA2 mutation. We undertook a case-control study to evaluate the effect of the cumulative number of ovulatory cycles and each of the contributing components) on the risk of developing breast cancer among BRCA mutation carriers.
Methods: A matched case-control study was conducted in 2,632 pairs of women with a deleterious mutation in either BRCA1 (n = 1,915 pairs) or BRCA2 (n = 717 pairs). Women diagnosed with breast cancer were matched to unaffected control subjects by year of birth, mutation status, and country of residence. Information about reproductive factors, hormonal exposures and menopausal status was collected from a routinely administered questionnaire and was used to estimate the cumulative number of ovulatory cycles. Conditional logistic regression was used to estimate the association between various exposures and the risk of breast cancer.
Results: The risk of breast cancer decreased with the number of ovulatory cycles (ρ = −0.69;P = 0.03). Age at menarche and breastfeeding were inversely related with risk of breast cancer among BRCA1 (P-trend &lt; 0.0001) but not BRCA2 (P-trend ≥ 0.36) mutation carriers. Parity, oral contraceptive use, and the number of ovulatory cycles, were not associated with risk (P-trend ≥ 0.21). The reduction in breast cancer risk associated with surgical menopause (OR = 0.49; 95%CI 0.37–0.64; P-trend &lt; 0.001) was stronger than that conferred by natural menopause (OR = 0.78; 95%CI 0.58–1.06; P-trend = 0.11). There was a significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR = 0.13; 95%CI 0.02–0.54; P = 0.006).
Conclusions: These data challenge the prevailing hypothesis that the risk of breast cancer in a woman can be predicted by her lifetime number of ovulatory cycles in women with a BRCA1 or BRCA2 mutation. Reproductive risk factors, such as age at menarche and breastfeeding are important in BRCA1, but not BRCA2 carriers. The observation that a postmenopausal oophorectomy protects against breast cancer is consistent with either a direct carcinogenic activity of ovarian androgens or through aromatization of androgen to estrogen. It is important to distinguish between these two possibilities because of the different implications for chemoprevention.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A65.
Abstract A93: Daily aspirin use and cancer mortality in a large United States cohort
Authors: Jacobs Eric J. , Newton Christina C. , Thun Michael J. , Gapstur Susan M. 
Published: June 2012

Abstract
Background: A recent pooled analysis of several randomized trials of daily aspirin for prevention of vascular events reported a 34% reduction (95% confidence interval (CI): 0.50–0.87) in overall cancer mortality during follow-up after five years on aspirin. However, some uncertainty remains about the magnitude of the effect of daily aspirin use, particularly long-term use, on cancer mortality.
Methods: We examined the association between daily aspirin use and overall cancer mortality among 100,140 men and women in the Cancer Prevention Study II Nutrition Cohort with no history of cancer. Hazard ratios (HRs) were calculated adjusting for smoking and other risk factors. Results: During follow-up between 1997 and 2008, 5,138 participants died from cancer. Compared to no use, daily aspirin use at baseline in 1997 was associated with slightly lower cancer mortality (HR = 0.93, 95% CI: 0.86–1.00), although this association was not formally statistically significant and did not vary by duration of daily use (HR = 0.93, 95% CI: 0.85–1.01 for &lt; 5 years use, HR = 0.94, 95% CI: 0.85–1.03 for ≥ 5 years use). In time-dependent analyses including 3,373 cancer deaths and using updated information from periodic follow-up questionnaires, daily aspirin use was associated with lower cancer mortality, but results did not differ by duration (HR = 0.84, 95% CI: 0.76–0.94 for &lt; 5 years, HR = 0.85, 95% CI: 0.76–0.96 for ≥ 5 years). Associations between daily aspirin use and cancer mortality appeared similar for low-dose and adult-strength aspirin.
Conclusions: These results are consistent with an association between recent daily aspirin use and modestly lower cancer mortality, but suggest any reduction in cancer mortality may be smaller than that observed with long-term aspirin use in the pooled trial analysis.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A93.
Abstract B103: Effect of over-the-counter vitamin D supplementation on circulating 25-hydroxyvitamin D concentration
Authors: Hibler Elizabeth , Hu Chengcheng , Jurutka Peter , Martinez M. Elena , Wagoner Chad , Jacobs Elizabeth 
Published: June 2012

Abstract
Background: Vitamin D is a proposed chemopreventive and treatment agent for a variety of cancers. Studies have identified cellular anti-cancer mechanisms as well as associations between low circulating 25(OH)D levels and increased risk of cancer. Recommendations exist for vitamin D supplementation, though published cholecalciferol supplement trials have tested only pharmacological preparations or multivitamins. It is unknown whether intake of over-the-counter (OTC) cholecalciferol supplements, at the estimated average requirement (EAR) recommended by the Institute of Medicine (IOM), changes circulating vitamin D metabolite concentrations and associated biomarkers in healthy adults.
Objective: To determine the effect of 400 IU of OTC cholecalciferol supplements on circulating 25(OH)D concentrations in healthy adults.
Methods: This study was a blinded, randomized, placebo-controlled trial conducted from September 2009 through March 2010 in Tucson, Arizona. A total of 60 healthy male and female residents, aged 35 to 50 years, were recruited. Participants were randomized to receive either 400 IU/d cholecalciferol or a placebo for 30 days. Serum samples were collected every 15 days (± 3 days) and analyzed to determine if the change in circulating 25(OH)D concentration was significantly different between the groups.
Results: After 30 days of supplementation, the net change in circulating concentration of 25(OH)D in the supplement versus placebo group was 2.2 ng/ml (8.5% change, p-value = 0.06). Individuals with low baseline 25(OH)D (&lt;20 ng/ml) had a net change of 4.0 ng/ml (24.4% change, p-value = &lt;0.01), while participants with higher baseline concentration (&gt;30 ng/ml) did not increase significantly (net change 0.3 ng/ml, 0.8%, p-value = 0.84).
Conclusions: Use of OTC cholecalciferol supplements is a common practice, yet there is limited evidence to demonstrate the effectiveness of OTC vitamin D supplements to change circulating 25(OH)D levels. These initial results demonstrate that 400 IU OTC cholecalciferol is sufficient for maintaining the 25(OH)D concentrations of Arizonans throughout the winter, and provide support for the IOM recommended EAR of 400 IU/day in this population. Further research on the optimal dose for chemoprevention is ongoing.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B103.
Abstract B19: Mouth cancer awareness in Grampian region of Scotland, UK
Authors: Macfarlane Tatiana V. , Cunningham Claudia , Bovaird Iain , Morgan Rochelle , Watkins Ray 
Published: June 2012

Abstract
Aim: The purpose of this project was to determine the level of mouth cancer awareness and to investigate the associated factors in a UK general population sample.
Material and Methods: A Dental Health Survey was conducted on 3,353 adult residents in the Grampian region of the UK (adjusted participation rate 58%). Participants completed a questionnaire consisting of questions on oral health, behaviour, quality of life and cancer awareness.
Results: Overall, 81% of participants reported that they were aware of mouth cancer. Mouth cancer awareness was related to younger age (P&lt;0.001), higher levels of education (P&lt;0.001) and better general health (P&lt;0.001). There was no significant association found with gender, deprivation, rurality, oral health or mouthwash use. However, current smokers and participants who consumed alcohol every day were more aware of mouth cancer (P=0.004 and P&lt;0.001 respectively). When asked about risk factors for mouth cancer the following were identified: smoking (84%), poor oral hygiene (60%), drinking alcohol heavily (59%), poor diet (37%), stress (15%), being overweight (6%), drinking hot liquids (5%), eating spicy food (3%), using mouthwash (2%) and kissing someone (1%). Smokers were more likely to indentify smoking as a risk factor for mouth cancer (P=0.016). Similarly, those who consumed alcohol daily were more likely to identify heavy alcohol drinking as a risk factor (P&lt;0.001).
Conclusions: Awareness of mouth cancer is high in respondents from the general population and participants were able to identify the most important risk factors. Knowledge of tobacco and alcohol as risk factors was highest amongst those exposed to them. This study demonstrated that the focus of prevention needs to be on efforts to change health behaviour rather than increasing knowledge.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B19.
Abstract B26: Vaginal health assessment study for breast cancer survivors
Authors: Sutherland Elena I. , Feng Lei , Newman Lonzetta L. , Cook Elise Donaville 
Published: June 2012

Abstract
Postmenopausal breast cancer survivors often have urogenital atrophy adversely affecting their quality of life. Symptoms of atrophic vaginitis include: vaginal irritation, dyspareunia, postcoital bleeding, and increased susceptibility to vaginal infections. Endocrine breast cancer therapies further decrease estrogen levels, exacerbating these symptoms. Current non-hormonal vaginal therapies used first-line are often given with vague instructions, or not given at all. Hormonal therapies including estrogen and progesterone may increase the risk of recurrence and are therefore rarely used. This scenario results in breast cancer patients not having resolution of their atrophic vaginitis symptoms. There is a lack of data for atrophic vaginitis symptoms reported by patients and treatments employed in this population of breast cancer survivors. Therefore, we conducted a pilot study of urogenital symptoms in breast cancer survivors.
This is prevalence, cross-sectional study of female patients from the Breast Survivorship Clinic in the Cancer Prevention Center at the UT M.D. Anderson Cancer Center. Patients included in this study are women with a history of invasive breast cancer and are greater than five years after treatment; women with ductal carcinoma in situ (DCIS) are at least six months after treatment.
Approximately 1000 individual patient's charts (over 4,800 clinic visits) were available for review during the time frame studied (July 1, 2010 to June 30, 2011). Two predefined age groups will be evaluated (&lt;60, 60–75), focusing on the patients younger than 60 years of age.
Taking the information from the chart review, we will present the number of breast cancer female patients reporting symptoms of atrophic vaginitis. We will also report the percent of patients with symptoms who actually get treatment and the types of treatment recommended and prescribed.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B26.
Abstract B49: Prevention of colitis-associated colorectal cancer with 8-hydroxydeoxyguanosine
Authors: Han Young-Min , Ock Chan Young , Kim Eun-Hee , Hong Hua , Hong Kyung-Sook , Choi Ki-Seok , Hahm Ki Baik , Chung Myung-Hee 
Published: June 2012

Abstract
Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or anti-oxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3 which are significantly up-regulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-OHdG) paradoxically can block Rac1 activation and subsequent NOX inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS) induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which IL-10 knock-out mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2 and iNOS in a dose-dependent manner. In order to document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-contained diets were given for 20 weeks. As results, mice which consumed 8-OHdG-contained-diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in 8-OHdG treated group. Significantly decreased levels of MDA, MCP-1, MMPs, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer preventive effect of exogenous 8-OHdG against CAC.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B49.
Abstract B53: Chromatin remodeling as a new target for cancer chemoprevention
Authors: Peng Guang , Pan Mei-Ren , Lin Shiaw-Yih 
Published: June 2012

Abstract
Chromatin remodeling complexes use the energy of ATM hydrolysis to dynamically regulate the structure of chromatin. Growing evidence indicates that these complexes have a widespread role in tumor suppression. However, the mechanisms by which aberrations in these complexes drive tumorigenesis remain largely unknown. In addition to their well-established role in gene transcriptional control, our recent studies provide a novel linkage between chromatin remodeling and homologous recombination (HR)-mediated DNA repair in the maintenance of genomic stability.
Our results showed that an evolutionarily conserved chromatin remodeling complex SWI/SNF is targeted to DNA damage lesions via an interaction with BRIT1, an early DNA damage responsive protein. Chromatin remodeling activity is required for relaxing highly condensed chromatin and facilitating the loading of HR repair proteins to conduct efficient HR repair. Furthermore, our unpublished data identified that another remodeling complex CHD4 functions as an upstream regulator of HR repair by recruiting BRIT1 and BRCA1 to DNA lesions. As a functional consequence of impaired HR repair, our data indicated that cells with depletions of chromatin remodeling complexes SWI/SNF and CHD4 show hypersensitivity to a new class of drugs poly ADP ribose polymerase (PARP) inhibitors via a synthetic lethal interaction.
In conclusion, our studies reveal the interplay between epigenetic regulation and genome maintenance. Chromatin remodeling affects HR repair process, which may lead to the changes in the DNA coding sequencing that are inheritable through cell division. Moreover, Deficient HR repair has been well known to predispose to cancer development, which is highlighted by mutations of HR repair genes BRCA1/BRCA2 in breast and ovarian cancers. Our findings may have important clinical implications in cancer prevention. Chromatin remodeling complexes, such as SWI/SNF and CHD4 might be used as epigenetic markers for prognosis, and prediction in early stage of tumorigenesis, and also for targeted preventive intervention by using PARP inhibitors.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B53.
Abstract B68: Curcumin-induced expression of 15-hydroxyprostaglandin dehydrogenase in normal gastric mucosa RGM-1 cells: Possible involvement of AP-1
Authors: Lee Young Wook , Jang Ji-Hye , Park Jong-Min , Surh Young-Joon , Na Hye-Kyung 
Published: June 2012

Abstract
Overproduction of prostaglandin E2 (PGE2) has been reported to be implicated in carcinogenesis. The intracellular level of PGE2 is regulated not only by its biosynthesis, but also by the degradation process. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme that catalyzes the first step in the inactivation of PGE2. In the present study, we have found that curcumin, a yellow colouring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH in normal rat gastric mucosa cells (RGM-1) in a concentration and time dependent manner. The mRNA level of 15-PGDH was also increased by curcumin treatment. By using deletion constructs of 15-PGDH promoter, we found that activator protein-1 (AP-1) is the most essential transcription factor responsible for curcumin-induced upregulation of 15-PGDH expression. Curcumin induced phosphorylation of ERK1/2 and JNK1/2, but did not affect activation of p38 MAP kinase. However, treatment with U0126 and SP600125, pharmacological inhibitors of ERK and JNK, respectively failed to suppress the induction of 15-PGDH expression in curcumin-treated RGM-1 cells. Curcumin enhanced the expression of c-Jun, c-fos and CREB in the nuclear fraction of RGM-1 cells. In contrast, tetrahydrocurcumin which lacks the α,β-unsaturated carbonyl group failed to induce expression 15-PGDH, suggesting that the electrophilic α,β-unsaturated carbonyl group of curcumin plays a critical role in its induction of 15-PGDH expression in RGM-1 cells. These results suggest that curcumin-induced expression of 15-PGDH may be mediated by activation of AP-1 transcription factor.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B68.