bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2271: DNMT1 expression is peripheral mononuclear cells is associated with increased breast cancer risk
Authors: Delgado-Cruzata Lissette , Ma Xinran , Liao Yuyan , Kappil Maya , Santella Regina M. , Terry Mary Beth 
Published: July 2017

Abstract
Loss of global DNA methylation in peripheral tissue has been identified as a biomarker of breast cancer susceptibility in several studies. DNA methyl-transferases or DNMTs are the enzymes in charge of catalyzing the addition of the methyl group to the DNA molecule. Of the different DNMTs described in humans, only DNMT1 has been found to be in charge of adding methyl groups to the newly synthesized DNA strand. Therefore, compromised levels of this enzyme might lead to a loss of global DNA methylation and concomitantly an increase in breast cancer risk. However, to date no study has examined the association between peripheral levels of DNMT1 and breast cancer. To investigate this relation, we conducted a case-control study including sisters in the New York site of the Breast Cancer Family Registry. We extracted mRNA from peripheral mononuclear cells (PMNC) in 196 sister sets, a total of 479 female participants, and assayed DNMT1 gene expression levels using Taqman expression assays. The results were analyzed using generalized estimating equations (GEE). We found that there were no large differences between the mean levels of DNMT1 expression levels of women with breast cancer and controls; mean level in cases was 0.46 ± 0.71 versus 0.63 ± 1.42 in controls (p=0.10). When examining expression levels as a continuous variable, there also were no associations in GEE regression models adjusting for age at blood drawn and smoking status Odds Ratio (OR) = 1.17 (95% confidence interval (CI) = 0.97 - 1.40 per one unit increase in expression levels), p=0.11). However, when results were analyzed by categorizing DNMT1 expression in tertiles, lower DNMT1 expression (≤ 0.17%) was associated with statistically significantly higher odds of breast cancer (OR = 1.47 (95%CI = 1.02 - 2.10), p=0.04). If replicated in other studies, these findings suggest that low DNMT1 expression in PBMC has the potential to be used as a biomarker of breast cancer risk in women at high risk of the disease.
Citation Format: Lissette Delgado-Cruzata, Xinran Ma, Yuyan Liao, Maya Kappil, Regina M. Santella, Mary Beth Terry. DNMT1 expression is peripheral mononuclear cells is associated with increased breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2271. doi:10.1158/1538-7445.AM2017-2271
Abstract 2274: Extreme telomere length was associated with gastric adenocarcinoma risk: The Singapore Chinese Health Study
Authors: Wang Zhensheng , Koh Woon-Puay , Jin Aizhen , Wang Renwei , Yuan Jian-Min 
Published: July 2017

Abstract
Background: Evidence regarding extreme telomere length and increased gastric cancer risk has been limited in retrospective case-control study setting which was potentially subjected to selection bias and reverse causality. We conducted a prospective analysis in an Eastern Asian population to examine the hypothesis that extreme telomere length is associated with increased risk of gastric adenocarcinoma.
Methods: Among 63,257 participants of the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women aged 45-74 years recruited between 1993 and 1998, 28,219 provided baseline blood samples. We used quantitative polymerase chain reaction (PCR) method to quantify relative telomere length determined by the ratio of telomere repeat copy number (T) to single-copy gene for albumin (S) (i.e., TSR) on all subjects. The present analysis included 24,846 subjects with valid TSR values after excluding samples with insufficient DNA (n = 1,908) and/or patients with prevalent cancer at baseline blood draw (n = 1,465). As of December 31, 2014, 191 study participants who were free of cancer developed gastric adenocarcinoma. The information on demographic and lifestyle characteristics was collected using structured questionnaires at baseline and two follow-up interviews. Cox proportional
hazard regression method was used to estimate hazard ratio (HR) and the corresponding 95% confidence interval (CI) of developing gastric adenocarcinoma for different levels of decile TSR. Restricted cubic spline (RCS) analysis was applied to examine the nonlinear relationship between TSR level and gastric adenocarcinoma risk.
Results: The RCS analysis revealed a U-shaped relationship between TSR and gastric adenocarcinoma risk (p-value for non-linear association=0.009). Compared with the 4th decile, HR (95% CI) for the lowest and highest deciles of TSR 2.27 (1.17-4.40) and 1.98 (0.95-4.13), respectively after adjusting for age, sex, education, interview year, dialect group and smoking status.
Conclusions: This was the first prospective analysis of TSR and risk of developing gastric adenocarcinoma in a general population. The study demonstrates both extreme short and long telomere length to be associated with significantly increased risk of gastric adenocarcinoma. These results suggest a complex relationship between telomere length and gastric cancer risk.
Citation Format: Zhensheng Wang, Woon-Puay Koh, Aizhen Jin, Renwei Wang, Jian-Min Yuan. Extreme telomere length was associated with gastric adenocarcinoma risk: The Singapore Chinese Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2274. doi:10.1158/1538-7445.AM2017-2274
Abstract 228: Identification of a novel biomarker to predict castration-resistant prostate cancer (CRPC) by the proteome analysis
Authors: Uemura Hiroji , Arakawa Noriaki , Itoh Yusuke , Kawahara Takashi , Miyoshi Yasuhide , Yao Masahiro , Akiba Shouhei , Ohtake Norihisa 
Published: July 2017

Abstract
Prostate specific antigen (PSA) is useful for screening prostate cancer, while it has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for castration resistant prostate cancer (CRPC). In order to explore novel biomarkers to predict the development of CRPC, we performed proteomics from secreted proteins from human prostate cancer cells and identified the candidates of biomarker for CRPC.
Materials and Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured.
Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDPP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDPP, was significantly higher in CRPC than those in BPH and untreated PCa (P&lt;0.01). ROC analysis also showed that the AUC of GDPP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDPP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDPP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDPP-1 may be a novel biomarker for CRPC.
Conclusion: GDPP-1 shows potential as a novel biomarker for CRPC.
Citation Format: Hiroji Uemura, Noriaki Arakawa, Yusuke Itoh, Takashi Kawahara, Yasuhide Miyoshi, Masahiro Yao, Shouhei Akiba, Norihisa Ohtake. Identification of a novel biomarker to predict castration-resistant prostate cancer (CRPC) by the proteome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 228. doi:10.1158/1538-7445.AM2017-228
Abstract 2288: Effects of tobacco smoking and alcohol consumption on risks of CYP1B1 polymorphisms for prostate cancer
Authors: Kato Taku , Hashimoto Yutaka , Maekawa Shigekatsu , Shiina Marisa , Imai-Sumida Mitsuho , Dasgupta Pritha , Kulkarni Priyanka , Yamamura Soichiro , Majid Shahana , Saini Sharanjot , Sharryari Varahram , Deng Guoren , Dahiya Rajvir , Tanaka Yuichiro 
Published: July 2017

Abstract
Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and polymorphic variants have been shown to increase activity levels. Lifestyle choices such as tobacco smoking and alcohol consumption are known to enhance the carcinogenesis process and in this study, how these factors may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population consisting of 405 healthy men and 400 prostate cancer patients were obtained. Of these, 507 were current or former smokers and 407 were alcohol drinkers. Eight polymorphic sites of the promoter region of CYP1B1 (rs2551188 G to A, rs2567206 G to A, rs2567207 A to G, rs162556 A to G, rs10175368 C to T, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed in samples using Taqman genotyping assays and real-time PCR. Lifestyle factors and its influence on CYP1B1 polymorphisms toward cancer risks were also evaluated. Overall, both alcohol (P=0.006) and smoker (P=0.069) status were associated with prostate cancer. CYP1B1 variants were also risks for cancer at rs2551188 (P=0.043), rs2567206 (P=0.008), and rs10175368 (P=0.001). Evaluation of linkage disequilibrium show rs2551188, rs2567206, rs2567207, and rs10175368 to be linked and interestingly, the G-G-A-C haplotype (wildtype at respective sites) was significantly reduced in cancer (P=0.0282). When classified by lifestyle factors, no associations for CYP1B1 variants were found for cancer among non-smokers with rs10175368 (P=0.051) being a risk among non-drinkers. On the other hand, variants at both rs2567206 and rs10175368 showed increased cancer risk among smokers (P=0.032 and 0.002, respectively) as well as drinkers (P=0.044 and 0.019, respectively). No genotyping differences were observed when analyzing cancers by pathological grades. These results demonstrate smoker and alcoholic drinker status to modify the risks of CYP1B1 polymorphisms for prostate cancer and this is of importance in understanding their role in the pathogenesis of this disease.
Citation Format: Taku Kato, Yutaka Hashimoto, Shigekatsu Maekawa, Marisa Shiina, Mitsuho Imai-Sumida, Pritha Dasgupta, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Varahram Sharryari, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Effects of tobacco smoking and alcohol consumption on risks of CYP1B1 polymorphisms for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2288. doi:10.1158/1538-7445.AM2017-2288
Abstract 2290: Perceived stressfulness of life events impacts breast cancer risk
Authors: Fischer Avital , Ziogas Argios , Anton-Culver Hoda 
Published: July 2017

Abstract
Background: Breast cancer is the most prevalent malignancy and the second most common cause of cancer mortality among women. Approximately 60% of variability in breast cancer risk remains unexplained. It is imperative to perform further research focusing on identifying preventable risk factors for breast cancer. The relationship between psychological stress and breast cancer risk is unclear. Psychological stress arises when environmental demands are appraised as going beyond one’s coping abilities. Higher perceived stress has been linked to increased cortisol levels and HPA perturbations. The purpose of this study is to understand the relationship between stressfulness appraisal of salient life events and breast cancer risk.
Methods: A case-control design was used and included 664 female cases identified through the Cancer Surveillance Program of Orange County, CA and 203 female population-based controls. Participants completed a risk factor questionnaire that included a life event section. Participants were asked to determine if events occurred and if they were considered to be significantly stressful or not. Multivariate unconditional logistic regression was used to calculate ORs while adjusting for known breast cancer covariates.
Results: Cumulative adverse life events perceived as stressful were associated with increased breast cancer risk in a dose response fashion (OR=1.63, 95% CI=1.00-2.66, Ptrend=0.045). Conversely, cumulative adverse life events not reported as stressful did not have a significant impact on breast cancer risk (OR=2.04, 95% CI=0.77-5.43). History of personal illness was directly related to increased breast cancer risk, when perceived as stressful (OR=2.84, 95% CI=1.96-4.11) or non-stressful (OR=3.47, 95% CI=1.34-8.94). Interestingly, abortion and relocation were observed to have a protective effect on breast cancer risk only when reported as being stressful (OR=0.54, 95% CI=0.32-0.92; OR=0.63, 95% CI=0.43-0.93 respectively).
Conclusions: This study broadens our understanding of the relationship between major life events and breast cancer risk and underscores the importance of stressfulness appraisal. Our results indicate the importance of incorporating assessments of perceived stressfulness in future epidemiological investigations focusing on the assessment of life events and breast cancer risk.
Note: This abstract was not presented at the meeting.
Citation Format: Avital Fischer, Argios Ziogas, Hoda Anton-Culver. Perceived stressfulness of life events impacts breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2290. doi:10.1158/1538-7445.AM2017-2290
Abstract 2296: Metformin reduces colon cancer risk in patients with type 2 diabetes: a retrospective cohort analysis
Authors: Tseng Chin-Hsiao 
Published: July 2017

Abstract
Background: The effect of metformin on colon cancer is rarely investigated in Asian populations.
Methods: This is a retrospective cohort study. Patients with newly diagnosed type 2 diabetes during 1999-2005 were recruited from Taiwan’s National Health Insurance. A 1:1 propensity score matched-pair sample of 16314 ever users and 16314 never users of metformin were followed until December 31, 2011. Cox regression incorporated with the inverse probability of treatment weighting using propensity score was used to estimate hazard ratios.
Results: The incidence of colon cancer was 272.04 and 392.44 per 100,000 person-years, respectively, in ever and never users. The overall hazard ratio (0.691, 95% confidence interval: 0.578-0.826) suggested a significantly lower risk in metformin users. While compared to never users, the hazard ratio (95% confidence interval) for the first (&lt;20.00 months), second (20.00-45.20 months) and third (&gt;45.20 months) tertile of cumulative duration of metformin therapy was 1.455 (1.165-1.816), 0.683 (0.526-0.885) and 0.224 (0.152-0.331), respectively. The protective effect of metformin on colon cancer was not affected by the use of aspirin and statin or the infection of Helicobacter pylori in additional analyses.
Conclusions: Metformin reduces colon cancer risk in patients with type 2 diabetes. The protective effect is more remarkable when the cumulative duration is more than 20 months.
Citation Format: Chin-Hsiao Tseng. Metformin reduces colon cancer risk in patients with type 2 diabetes: a retrospective cohort analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2296. doi:10.1158/1538-7445.AM2017-2296
Abstract 2298: Antibiotic use and breast cancer risk: results from the Sister Study
Authors: Deming-Halverson Sandra L. , Hodgson M. Elizabeth , D'Aloisio Aimee , Shore David , Sandler Dale 
Published: July 2017

Abstract
Background: Regular antibiotic use is hypothesized to influence breast cancer risk by a number of mechanisms including disruption of intestinal microflora which plays a role in the conversion of food-based phytochemicals into bioactive substances suggested to be protective against cancer, and by influences on the immune system and inflammatory response. Previous results have been mixed, and given the sparse and conflicting data in epidemiologic literature, we analyzed the association between regular antibiotic use and breast cancer risk, overall and by different classes of antibiotics.
Methods: Regular antibiotic use, as characterized by class type and number, duration, and indication for use, was evaluated for its association with breast cancer risk among participants of the NIEHS Sister Study, a prospective cohort of 50,884 US women aged 35-74 without breast cancer who have had a sister diagnosed with breast cancer.
Results: 5,312 (10.4%) of women in the Sister Study reported ever having regular antibiotic use (at least 3 times per week for 3 months in a row or longer) with a median duration of 1.50 years (0.25 – 53.8). 34% of regular uses reported use greater than 2 years. Skin conditions including acne and rosacea were the most common indications for use (6.02%). The hazard ratio (HR) was 1.10 (0.99-1.27) for ever regular antibiotic use and 1.40 (1.16-1.69) for greater than 2 years of regular use. Results are suggestive of an increased risk among regular users who have only ever used one class rather than more than one class of antibiotics. Adjusted hazard ratios were 1.40 (0.99-1.99) for tetracyclines only, 1.45 (0.95-2.20) for penicillins only, 1.42 (0.94-2.15) for macrolides alone. However, there does not appear to be an association between ever regular use of more than one class of antibiotics and breast cancer. Furthermore, there was no association between indications for ever regular use and breast cancer risk, among all women reporting regular use of antibiotics, regardless of class.
Conclusion: Overall, there is a suggestion that ever regular use of a single class of antibiotics, but not use of more than one class, may be associated with increased breast cancer risk. However, given that most individuals reported only a single episode of regular antibiotic use for a duration of less than 2 years; further exploration is warranted to rule out effects of underlying indication for use or explore other possible class specific-confounders.
Citation Format: Sandra L. Deming-Halverson, M. Elizabeth Hodgson, Aimee D'Aloisio, David Shore, Dale Sandler. Antibiotic use and breast cancer risk: results from the Sister Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2298. doi:10.1158/1538-7445.AM2017-2298
Abstract 2305: Residential airborne heavy metal concentrations and breast cancer characteristics
Authors: Kresovich Jacob K. , Erdal Serap , Argos Maria , Chen Hua Yun , Gann Peter H. , Rauscher Garth H. 
Published: July 2017

Abstract
Background: Ambient air metal concentrations have recently been implicated in the etiology of breast cancer. Previous studies have shown airborne concentrations of arsenic and cadmium are associated with the development of estrogen receptor-negative tumors. This study aims to replicate these findings and examine the role of other toxic and essential heavy metals.
Methods: Participants were women who were diagnosed with breast cancer in Chicago between 2005 and 2008. We examined estrogen and progesterone receptor-negative (ER-/PR-) and high-grade tumors as markers of aggressive breast cancer, and estimated 15-year markers of exposure of 11 heavy metals. Exposures were calculated using census tract-level airborne concentrations from the National-scale Air Toxics Assessment and participants’ residential histories. We adjusted all models for socioeconomic status and reproductive factors.
Results: We found that prevalent ER-/PR- tumors were associated with increased residential exposure to airborne concentrations of antimony (Q4 vs Q1: OR= 1.81; 95% CI: 0.95, 3.44; Ptrend= 0.04), cobalt (Q4 vs Q1: OR= 2.37; 95% CI: 1.26, 4.45; Ptrend &lt; 0.01), manganese (Q4 vs Q1: OR= 2.55; 95% CI: 1.24, 5.24; Ptrend= 0.04), and selenium (Q4 vs Q1: OR= 1.85; 95% CI: 1.03, 3.29; Ptrend= 0.05), and also identified marginally significant trends for arsenic (Ptrend= 0.06), chromium (Ptrend= 0.08), lead (Ptrend= 0.08), and mercury (Ptrend= 0.07). We did not identify any overall associations with high-grade tumors, however when stratifying by menopausal status we found that antimony (Q4 vs Q1: OR= 6.97, 95% CI: 1.61-30.19) and arsenic (Q4 vs Q1: OR= 6.97, 95% CI: 1.61-30.19) were associated with prevalent high-grade tumors in premenopausal women only.
Discussion: This study found further support for a role of airborne arsenic concentrations, and novel evidence implicating other airborne estrogen-pathway disrupting metal concentrations, in the development of aggressive breast cancer subtypes. Additionally, this is the first study to implicate heavy metal exposure in the etiology of high-grade tumors. These results suggest that long-term, low-dose exposures to certain heavy metals play a role in the etiology of aggressive breast cancer characteristics. Airborne exposures have the ability to affect large populations and findings from this and similar studies have large public health implications.
Citation Format: Jacob K. Kresovich, Serap Erdal, Maria Argos, Hua Yun Chen, Peter H. Gann, Garth H. Rauscher. Residential airborne heavy metal concentrations and breast cancer characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2305. doi:10.1158/1538-7445.AM2017-2305