bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR-12: Is the screening-related increase of breast cancer mainly caused by lesions that would undergo spontaneous regression if left untreated?
Authors: Zahl Per-Henrik , M?hlen Jan 
Published: May 2012

Abstract
PR-12

Objective
In Norway mammography screening is associated with a 50% long-term increase of the incidence of invasive breast cancer. Based on an analysis of incidence data from the Norwegian screening program, we have recently argued that the majority of these extra cancers would have undergone spontaneous regression in the absence of screening (Zahl PH, Mæhlen J, Welch HG. The natural history of breast cancer detected by screening mammography. Archives of Internal Medicine 2008; Nov 24th). At mammography a large number of ductal carcinoma in-situ (DCIS) are detected and treated as low grade cancer. The objective of the present study is to repeat this analysis on a data set containing both invasive cancer and DCIS.

Materials and Methods
The data from the Norwegian Cancer Registry include invasive cancer and DCIS from the last 16 years for women of four counties in which the age group 50-69 years (n =166 000) was been invited to biennial mammography screening from 1996. We compared the 6-year cumulative incidence in two age matched and partly overlapping cohorts. The first cohort (the test group) included women born 1932-46 invited biennially during the 6-year observation period 1996-2001. The second cohort (the control group) included women born 1928-42 and invited once at the end of the 6-year observation period 1992-97. Note that for both cohorts the age span was 50-64 years at the start of the respective observation periods.

Results
The 6-year cumulative incidence of invasive cancer and DCIS combined was 28 % higher in the first cohort than in the second cohort. (2206 vs. 1739 per 100 000; RR = 1.27 (95% CI: 1.20 - 1.34). A sensitivity analysis of the potential effect of HRT showed that at most 2% of the 27% difference could be explained by differences in the HRT use. We also tested if low sensitivity could explain the difference - it could not explain the difference (P&lt;0.001).

Conclusion
We have shown that the screening related incidence increase in the first four years of the 6-year observation period in the first cohort is not compensated for by a corresponding incidence increase when the previously un-screened women in the second cohort were invited in year 5-6. Increasing use of HRT and low sensitivity in the screening did not explain the difference. We propose that most of the screening-related incidence increase of invasive cancers and DCIS is due to tumors that in the absence of screening would have undergone spontaneous regression.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-12.
Abstract PR-3: A novel function of poly(ADP-ribose) polymerase-1 in modulation of autophagy and necrosis under oxidative stress
Authors: Huang Qing , Wu You-Tong , Tan Hui-Ling , Ong Choon-Nam , Shen Han-Ming 
Published: May 2012

Abstract
PR-3
Under oxidative stress, poly(ADP-ribose) polymerase-1 (PARP-1) is activated and contributes to necrotic cell death through ATP depletion. On the other hand, oxidative stress is known to stimulate autophagy, and autophagy may act as either a cell death or cell survival mechanism. This study aims to explore the regulatory role of PARP-1 in oxidative stress-mediated autophagy and necrotic cell death. Here we first show that hydrogen peroxide (H2O2) induces necrotic cell death in Bax-/- Bak -/- mouse embryonic fibroblasts (MEFs) through a mechanism involving PARP-1 activation and ATP depletion. Next, we provide evidence that autophagy is activated in cells exposed to H2O2. More importantly, we identify a novel autophagy signaling mechanism linking PARP-1 to the serine/threonine protein kinase LKB1-AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway, leading to stimulation of autophagy. Finally, we demonstrate that autophagy plays a cytoprotective role in H2O2-induced necrotic cell death as suppression of autophagy by knockdown of autophagy-related gene ATG5 or ATG7 greatly sensitizes H2O2-induced cell death. Taken together, these findings demonstrate a novel function of PARP-1: promotion of autophagy via the LKB1-AMPK-mTOR pathway to enhance cell survival in cells under oxidative stress.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-3.
Abstract PR-8: Trichomonas vaginalis infection and prostate cancer incidence and mortality: A prospective study in the Physicians’ Health Study
Authors: Stark Jennifer , Judson Gregory , Alderete John , Sutcliffe Siobhan , Mundodi Vasanthakrishna , Kucknoor Ashwini , Giovannucci Edward , Platz Elizabeth , Fall Katja , Kurth Tobias , Ma Jing , Stampfer Meir , Mucci Lorelei 
Published: May 2012

Abstract
PR-8

Background
Several inflammation-related factors have been implicated in prostate cancer risk and progression, but the origin of inflammation is unclear. Infections are one possible source, but studies of specific infections have been largely inconclusive. A recent prospective study found that antibody seropositivity against Trichomonas vaginalis was positively associated with subsequent incidence of prostate cancer. This parasitic protozoan has received relatively little attention despite being the most common non-viral sexually transmitted infection. We sought to further explore and extend this hypothesis in an independent population, both for prostate cancer incidence as well as progression.

Methods
We conducted a prospective case-control study nested within the Physicians’ Health Study that included 673 prostate cancer cases and 673 individually matched controls. T. vaginalis antibody serostatus was assessed by an ELISA that detects IgG antibodies against purified, recombinant T. vaginalis α-actinin protein. We used conditional logistic regression for analyses of total prostate cancer incidence and Cox proportional hazards models to estimate hazard ratios for lethal prostate cancer (prostate cancer-specific death or development of bony metastases).

Results
The seroprevalence of T. vaginalis infection was 21% in controls and 25% in cases. Among cases, the average time between blood draw and prostate cancer diagnosis was 9.3 years (range 0.3 years - 17.9 years). Though not statistically significant, the magnitude of the association between T. vaginalis seropositivity and overall prostate cancer risk (OR: 1.23; 95% CI: 0.94, 1.61) was similar to the original study, which observed a 43% increased risk. Further, seropositive men had a 2.2-fold increase in risk of extraprostatic disease (95% CI: 1.08, 4.37) and a 2.7-fold greater risk of lethal prostate cancer (95% CI: 1.37, 5.28; 39 cases developed bony metastases or died of prostate cancer). Time-to event analyses included 7,776 person-years of follow-up and showed that, compared to seronegative cases, cases with serologic evidence of infection prior to cancer diagnosis had a 50% greater rate of progression to lethal prostate cancer (95% CI: 1.01, 2.16).

Conclusions
In this large prospective study, we observed a modest association between anti-T. vaginalis antibodies and overall prostate cancer risk and found that T. vaginalis infection was principally associated with clinically relevant, potentially lethal disease. If our findings are confirmed, T. vaginalis infection may represent a common risk factor for which chemoprevention could reduce burden of aggressive prostate cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-8.
Abstract PR-9: Results of surveillance for hereditary pancreatic cancer using MRI(CP)
Authors: Vasen Hans , Wasser Martin , Bonsing Bert , van Mil Anneke , Hommes Daniel , Morreau Hans , de Vos Wouter 
Published: May 2012

Abstract
PR-9

Introduction
Surveillance for pancreatic cancer (PC) in high risk groups may lead to early detection and may improve overall survival. We screened for early pancreatic neoplasia in individuals with a p16- germline mutation or with a strong family history of PC (FPC).

Methods
Since 2000, high risk individuals were offered annual surveillance by Magnetic Resonance Imaging (MRI(CP)). In case of suspected lesions, surgery or additional follow up (FU) was provided. In case of doubt, the examination was repeated within 2-4 months.

Results
A total of 66 (28 M) individuals with an average age of 56 yrs (range: 40-72) were studied (60 from p16, six from FPC families). The median FU was 3.4 yrs (range: 0-7). In 20% of the patients, a (pre)malignant lesion was detected. Ductectasias or IPMN (intraductal papillary mucinous neoplasm) were identified in eight patients (12%). Three patients underwent a prophylactic partial resection of the pancreas; histology showed IPMN in one and PanIn-II lesions in two patients. Five patients (8%) were diagnosed with PC. Three asymptomatic patients underwent partial pancreatectomy. One patient had no evidence for residual disease after surgery. The second patient had positive resection margins and nodes but survived 21 months. The third patient had metastatic carcinoid at surgery (in addition to pancreatic cancer). The remaining two patients did not undergo surgery because of metastatic disease (pulmonary metastases of melanoma, metastatic pancreatic cancer).

Conclusion
(Pre)malignant lesions were identified in a high proportion of patients. Small lesions of a few mm can be detected by MRI(CP). In view of the substantial morbidity of pancreatic surgery, a major challenge is to decide at what stage and to what extent prophylactic surgery should be performed. Close observation of high risk groups provides valuable information on the natural history of neoplastic lesions in the pancreas.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-9.
Abstract SS02-02: Chemoprevention: Poised for Success
Authors: Greenwald Peter 
Published: May 2012

Abstract
SS02-02
AACR Frontiers in Cancer Prevention
Special Session: Achieving the Potential of Chemoprevention
Monday, November 17, 2008; 12:00-1:00pm
Abstract
Chemoprevention: Poised for Success
Peter Greenwald
National Cancer Institute
greenwald@nih.gov
Phase III trials to prevent breast, prostate and colo-rectal cancers demonstrate clearly that reducing cancer risk via chemoprevention is possible and merits major research investment in addition to a balanced approach to public and professional education about the potential benefits for many people. In September 2007, the FDA approved raloxifene to reduce the risk of breast cancer in post-menopausal women at high risk of the disease. Thus, based in large part on the breast cancer prevention trial with tamoxifen and the more recent STAR trial, there are now two drugs approved for the prevention of breast cancer. The Prostate Cancer Prevention Trial showed that men who took 5 mg of finasteride daily for 7 years had a 25% reduced risk of developing prostate cancer compared with men taking placebo. Subsequent studies provide reassurance that the drug was probably not causing high grade cancers in the finasteride group (an earlier concern), but rather finasteride may simply have made it easier to detect high-grade cancers. Seventy percent of colon polyps, including 92 % of advanced adenomas, were prevented by a combination of the investigational compound DFMO and the anti-inflammatory agent sulindac. As a group, these pivotal trials demonstrate that major reductions in risk for common cancers are possible by means of chemoprevention. Expansion of pre-clinical chemoprevention studies, exploratory investigational studies of pharmaceuticals and bioactive food compounds for cancer prevention, and phase I & II trials, together with increased attention to building public-private partnerships and professional and public interest, will help to grow this promising field of cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):SS02-02.
Abstract A10: Insulin resistance's effect on PSA level for prostate cancer screening
Authors: Park Jinho , Cho Belong 
Published: May 2012

Abstract
Introduction: Previous studies showed that BMI decreased serum PSA level. Insulin resistance in obesity is suggested one of reasons. The negative association between BMI and PSA level may be partially due to low testosterone concentration caused by obesity-related hormonal disturbances (decrease of sex-hormone binding globulin and increase of aromatase and IR)
Objective: To examine the effect of homeostasis model assessment of insulin resistance (HOMA) index on PSA level after adjusting prostate volume(PV) effect in a screening population.
Design: We performed multivariate linear regression and ANOVA to assess potential influencing factors in a cross-sectional study of 30- to 80-year-old Korean men who underwent routine checkups from 2004–2008 (n=3,320).
Main Outcome Measures: Associations between factor variables (BMI, HOMA Index, PV) and PSA level assessed by trends tests by multivariate linear regression and/or ANOVA.
Results: PSA level was negatively associated with BMI before (P for trend &lt;.01) and after (P for trend by quartile &lt;.05 for all) PV stratification, but not associated with HOMA index before (P for trend &gt;.05) and after (P for trend by quartile &gt;.05 for all) PV stratification.
Conclusions: BMI has negative effect on PSA level irrespective of PV stratification, but IR had no association. Hemodilutional effect by obesity may be main cause of BMI's negative association on PSA level.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A10.
Abstract A105: Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue, and lung cancer risk
Authors: Lam Tram K. , Rotunno Melissa , Lubin Jay H. , Wacholder Sholom , Consonni Dario , Bertazzi Pier Alberto , Pesatori Angela C. , Chanock Stephen , Burdette Laurie , Goldstein Alisa M. , Tucker Margaret , Caporaso Neil E. , Subar Amy F. , Landi Maria Teresa 
Published: May 2012

Abstract
Background: Quercetin is a flavonol found in fruits (apple, grape) and vegetables (onion, broccoli). Quercetin possesses anticarcinogenic properties that protect against cancer. However, the epidemiological evidence on the association of quercetin-rich food intake with lung cancer risk is inconclusive, and how quercetin affects lung carcinogenesis in humans is largely unknown. Laboratory analyses have shown that quercetin may inhibit Phase I cytochrome P450s enzymes responsible for the activation of tobacco-related procarcinogens, and induce Phase II glutathione S-transferase (GST) enzymes responsible for the removal of activated carcinogens.
Methods: We investigated the role of dietary quercetin and the interaction between quercetin and P450 and GST polymorphisms on lung cancer risk in incident lung cancer cases and matched controls from Environment and Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study including 2100 primary lung cancer cases and 2120 controls. Dietary information and genotype data were available for 1740 cases and 1919 controls. In fresh-frozen non-tumor lung tissue from 38 adenocarcinoma patients, we also assessed the correlation between dietary quercetin intake and mRNA expression of tobacco-related Phase I and Phase II metabolic genes. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific quintile of intake were calculated using unconditional logistic regression, adjusted for putative risk factors. Two sample t-test was used to assess difference in expression by quercetin-rich consumption status.
Results: Frequent intake of quercetin-rich foods was inversely associated with lung cancer risk (ORQ5vsQ1=0.49;95% CI=0.37–0.67; p-trend: &lt;0.001), and did not differ by genotype, gender, or histological subtypes. The association was stronger in subjects who smoked more than 20 cigarettes per day (ORQ5vsQ1=0.35;95% CI=0.19–0.66; p-trend=0.003). The comparison between gene expression and high-versus-low consumption of quercetin-rich foods showed an overall down-regulation of P450 and up-regulation of GST metabolic genes (p-values&lt;0.05) in lung tissue.
Conclusions: Quercetin-rich diet was associated with lower risk of lung cancer and with down-regulation of Phase I P450 genes and up-regulation of Phase II GST genes in lung tissue. These findings suggest a possible mechanism for quercetin-related protection against lung cancer risk through quercetin-induced changes in the expression of genes involved in the metabolism of tobacco-carcinogens. Further studies exploring the interplay between quercetin intake, tobacco smoking, and lung cancer risk are warranted.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A105.
Abstract A107: Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies
Authors: Bao Ying , Ng Kimmie , Wolpin Brian M. , Michaud Dominique S. , Giovannucci Edward , Fuchs Charles S. 
Published: May 2012

Abstract
Background: Experimental data indicate that vitamin D has anticancer properties. However, epidemiologic studies on vitamin D and pancreatic cancer risk have yielded inconsistent results. We previously developed a model to predict long-term plasma 25-hydroxyvitamin D3 [25(OH)D] levels from multiple determinants of vitamin D status (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity as a surrogate of sunlight exposure). Here, we examine the association between predicted vitamin D status and pancreatic cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study.
Methods: We prospectively followed 118,597 participants in these two cohorts from 1986–2006. We calculated a 25(OH)D score from six predictors of vitamin D status for each individual using a multiple linear regression model and then examined the predicted 25(OH)D levels in relation to pancreatic cancer risk with Cox proportional hazards models. The multivariate models were adjusted for age, sex, race, height, smoking, and diabetes.
Results: During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH)D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH)D score had an adjusted RR of 0.65 (95% CI, 0.50–0.86; P for trend = 0.001). The results remained unchanged after further adjusting for BMI and physical activity or after excluding the first 2 years of follow-up. This inverse association was also consistent across gender and strata of other covariates, including age, region, smoking, BMI, and physical activity.
Conclusion: Higher 25(OH)D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A107.
Abstract A108: Serum retinol and risk of prostate cancer in the alphatocopherol, beta-carotene (ATBC) cancer prevention study
Authors: Mondul Alison M. , Watters Joanne L. , Virtamo Jarmo , Albanes Demetrius 
Published: May 2012

Abstract
Purpose: Retinol (vitamin A) may prevent prostate cancer by promoting cell differentiation and apoptosis, although under some conditions it could stimulate growth and de-differentiation. We examined serum retinol, measured at baseline and three years, in relation to prostate cancer risk in the ATBC Study.
Methods: The ATBC Study is a randomized controlled trial conducted to determine the effects of -tocopherol and s-carotene supplements on cancer incidence. 29,133 Finnish male smokers were recruited from 1985–1988 and were assigned to groups using a 2×2 factorial design: 1) -tocopherol, 2) β-scarotene, 3) both supplements, or 4) placebo. Fasting blood samples were collected at baseline and after 3 years, and as of April 30, 2006, 2,041 prostate cancer cases occurred during 417,532 person-years. Cox proportional hazards models were used to estimate the relative risk (as hazard ratio, HR) of total and aggressive (n=461) prostate cancer by quintile of baseline and 3-year serum retinol concentrations, as well as by change in serum retinol. No confounding by factors associated with either prostate cancer or retinol was observed.
Results: Men in higher quintiles of baseline retinol were more likely to develop prostate cancer compared with men in the lowest quintile (age-adjusted HR, 95%CI vs. Q1; Q2: 1.05, 0.91 – 1.21; Q3: 1.06 0.92 – 1.22; Q4: 1.13, 0.98 – 1.30; Q5: 1.19, 1.03 – 1.36; p-trend = 0.009). The association was similar for aggressive prostate cancer and when the 3-year retinol was used. Compared to men whose retinol did not differ between baseline and 3 years, men with either higher or lower retinol at follow-up were at similar risk of prostate cancer. When we jointly categorized men based on quintiles of baseline and 3-year retinol, we noted that men who were in the highest quintile of retinol at both time points had the greatest increased risk (baseline/3-year Q5/Q5 vs. Q1/Q1 HR: 1.31 95% CI: 1.08 – 1.59). Other joint categories were also at higher risk, particularly among men who did not receive the trial β-carotene supplement. Men randomized to the β-carotene arm had generally higher risk for any baseline/3-year retinol category compared to men in the no β-carotene arm, and those whose serum retinol decreased substantially from baseline Q4 or Q5 appeared to have a lower prostate cancer risk (HR, 95% CI vs. Q1/Q1; Q5 to Q1–3: 0.60, 0.35 – 1.03; Q4 to Q1–2: 0.85, 0.54 – 1.33).
Conclusion: In this largest study to date of serum retinol and prostate cancer that incorporates retinol measured at two time points three years apart, higher serum concentrations were associated with elevated risk, with sustained high exposure conferring the greatest risk. Distinct patterns of change in serum retinol over time may relate to differing risks of developing prostate cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A108.
Abstract A11: Development of minimally invasive techniques for monitoring genome health: A preventative health approach to reducing disease
Authors: O'Callaghan Nathan , Bull Caroline , Fenech Michael 
Published: May 2012

Abstract
It is becoming increasingly evident that risk for developmental and degenerative disease, including cancers, increases with more DNA damage. Importantly, DNA damage is influenced (and can be modified) by nutritional status. Optimal concentrations of nutrients for reduction of genome damage are also dependent on many factors (genetic background, age, nutrient uptake) that vary from individual to individual.
In the genomic health era of personalised nutrition for disease prevention, there is a need to develop minimally invasive methodologies to measure alterations in disease risk biomarkers in an effort to identify at risk individuals early in disease progression. Using qPCR techniques developed by us, we aimed to evaluate the use of buccal cells and saliva as a minimally-invasive approach to measure markers of genome health in a cross-sectional study.
Buccal cells, saliva and blood samples were collected from 91 volunteers. This cohort comprised 18M and 25F in the young group (aged 18–31 years), and 25M and 23F in the older group (65–75yrs). Telomere length was determined in lymphocytes, buccal cells and saliva (by qPCR). Telomere length was negatively correlated with age; the strength of this correlation varied between gender and tissue type.
We report that buccal cells and saliva can be used to measure DNA damage. Further research is required to evaluate the effectiveness of buccal cells and/or saliva as a minimally-invasive biomarker of oxidative DNA damage, genome health and disease risk status.
The development of dietary patterns, functional foods and supplements that are designed to improve genome-health maintenance in an individual with increased disease risk may lead to a preventative health strategy based on the diagnosis and individualised nutritional prevention of genome damage.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A11.