bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomere Length and Genetic Variation in Telomere Maintenance Genes in Relation to Ovarian Cancer Risk
Authors: Terry Kathryn L. , Tworoger Shelley S. , Vitonis Allison F. , Wong Jason , Titus-Ernstoff Linda , De Vivo Immaculata , Cramer Daniel W. 
Published: March 2012

Abstract
Background: Telomeres protect chromosomal ends, shorten with cellular division, and signal cellular senescence, but unchecked telomere attrition can lead to telomere dysfunction, upregulation of telomerase, and carcinogenesis. Shorter telomeres in peripheral blood leukocytes (PBL) have been associated with elevated cancer risk. Furthermore, genetic variants in and around the TERT gene have been implicated in carcinogenesis.
Methods: We measured relative telomere length (RTL) in PBLs of 911 cases and 948 controls from the New England case–control (NECC) study, a population-based study of ovarian cancer. In addition, we assessed germ line genetic variation in five telomere maintenance genes among 2,112 cases and 2,456 controls from the NECC study and the Nurses' Health Study, a prospective cohort study. ORs and 95% CIs were estimated by logistic regression.
Results: Overall, we observed no differences in telomere length between cases and controls. Compared with women with RTL in the longest tertile, women with RTL in the shortest tertile had no increase in risk (OR = 1.01, 95% CI: 0.80–1.28). However, several SNPs in the TERT gene, including rs2736122, rs4246742, rs4975605, rs10069690, rs2736100, rs2853676, and rs7726159, were significantly associated with ovarian cancer risk. We observed a significant gene-level association between TERT and ovarian cancer risk (P = 0.00008).
Conclusion: Our observations suggest that genetic variation in the TERT gene may influence ovarian cancer risk, but the association between average telomere length in PBLs and ovarian cancer remains unclear.
Impact: The role of telomeres in ovarian carcinogenesis remains unsettled and warrants further investigation. Cancer Epidemiol Biomarkers Prev; 21(3); 504–12. ©2012 AACR.
Tumor Suppressor Function of PGP9.5 Is Associated with Epigenetic Regulation in Prostate Cancer—Novel Predictor of Biochemical Recurrence after Radical Surgery
Authors: Mitsui Yozo , Shiina Hiroaki , Hiraki Miho , Arichi Naoko , Hiraoka Takeo , Sumura Masahiro , Honda Satoshi , Yasumoto Hiroaki , Igawa Mikio 
Published: March 2012

Abstract
Background: The expression level of protein G product 9.5 (PGP9.5) is downregulated because of promoter CpG hypermethylation in several tumors. We speculated that impaired regulation of PGP9.5 through epigenetic pathways is associated with the pathogenesis of prostate cancer.
Methods: CpG methylation of the PGP9.5 gene was analyzed in cultured prostate cancer cell lines, 226 localized prostate cancer samples from radical prostatectomy cases, and 80 benign prostate hyperplasia (BPH) tissues.
Results: Following 5-aza-2′-deoxycytidune treatment, increased PGP9.5 mRNA transcript expression was found in the LNCaP and PC3 cell lines. With bisulfite DNA sequencing, partial methylation of the PGP9.5 promoter was shown in LNCaP whereas complete methylation was found in PC3 cells. After transfection of PGP9.5 siRNA, cell viability was significantly accelerated in LNCaP but not in PC3 cells as compared with control siRNA transfection. Promoter methylation of PGP9.5 was extremely low in only one of 80 BPH tissues, whereas it was found in 37 of 226 prostate cancer tissues. Expression of the mRNA transcript of PGP9.5 was significantly lower in methylation (+) than methylation (−) prostate cancer tissues. Multivariate analysis of biochemical recurrence (BCR) after an radical prostatectomy revealed pT category and PGP9.5 methylation as prognostically relevant. Further stratification with the pT category in addition to methylation status identified a stepwise reduction of BCR-free probability.
Conclusion: This is the first clinical and comprehensive study of inactivation of the PGP9.5 gene via epigenetic pathways in primary prostate cancer.
Impact: CpG methylation of PGP9.5 in primary prostate cancer might become useful as a molecular marker for early clinical prediction of BCR after radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(3); 487–96. ©2012 AACR.
Genetic Susceptibility to Type 2 Diabetes and Breast Cancer Risk in Women of European and African Ancestry
Authors: Hou Ningqi , Zheng Yonglan , Gamazon Eric R. , Ogundiran Temidayo O. , Adebamowo Clement , Nathanson Katherine L. , Domchek Susan M. , Rebbeck Timothy R. , Simon Michael S. , John Esther M. , Hennis Anselm , Nemesure Barbara , Wu Suh-Yuh , Leske M. Cristina , Ambs Stefan , Niu Qun , Zhang Jing , Pierce Brandon , Cox Nancy J. , Olopade Olufunmilayo I. , Huo Dezheng 
Published: March 2012

Abstract
Background: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.
Methods: We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies.
Results: We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk.
Conclusion: The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist.
Impact: The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(3); 552–6. ©2012 AACR.
Tissue and Serum Mesothelin Are Potential Markers of Neoplastic Progression in Barrett's Associated Esophageal Adenocarcinoma
Authors: Rizk Nabil P. , Servais Elliot L. , Tang Laura H. , Sima Camelia S. , Gerdes Hans , Fleisher Martin , Rusch Valerie W. , Adusumilli Prasad S. 
Published: March 2012

Abstract
Background: Mesothelin is overexpressed in several malignancies and is purportedly a specific marker of malignant transformation. In this pilot study, we investigated whether tissue and serum mesothelin are potential markers of neoplastic progression in Barrett's esophagus (BE) and in esophageal adenocarcinoma (EAC).
Methods: Mesothelin expression was retrospectively evaluated in normal, BE, and EAC tissue from surgically resected esophageal specimens (n = 125). In addition, soluble mesothelin-related peptide (SMRP) levels were measured in serum.
Results: Normal esophageal mucosa did not express mesothelin. BE tissue with high-grade dysplasia specifically expressed mesothelin, whereas BE tissue with low-grade or without dysplasia did not. Fifty-seven (46%) EAC tumors were positive for mesothelin. EAC tumors with BE expressed mesothelin more often than those without BE (58% vs. 35%, P = 0.01). SMRP levels were elevated in 70% of EAC patients (mean = 0.89 nmol/L; range: 0.03–3.77 nmol/L), but not in patients with acid reflux and/or BE.
Conclusions: Mesothelin is commonly expressed in BE-associated EAC. On the basis of this pilot study, a prospective study is under way to evaluate tissue and serum mesothelin which are potential markers of neoplastic progression in BE and in EAC (NCT01393483).
Impact: Current surveillance methods in Barrett's esophagus are invasive and neither cost-effective nor sensitive. This pilot study suggests that serum mesothelin is a marker of neoplastic transformation in BE and may provide a noninvasive method to improve identification of malignant transformation. Cancer Epidemiol Biomarkers Prev; 21(3); 482–6. ©2012 AACR.
Milk and Dairy Consumption among Men with Prostate Cancer and Risk of Metastases and Prostate Cancer Death
Authors: Pettersson Andreas , Kasperzyk Julie L. , Kenfield Stacey A. , Richman Erin L. , Chan June M. , Willett Walter C. , Stampfer Meir J. , Mucci Lorelei A. , Giovannucci Edward L. 
Published: March 2012

Abstract
Background: Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated postdiagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow-Up Study.
Methods: The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate HRs and 95% CIs of the association between postdiagnostic milk and dairy intake and prostate cancer outcomes.
Results: We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15, 95% CI: 1.28–3.60; Ptrend &lt; 0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62; 95% CI: 0.40–0.95; Ptrend = 0.07).
Conclusions: With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer.
Impact: This is the first larger prospective study investigating the relation between postdiagnostic milk and dairy intake and risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(3); 428–36. ©2012 AACR.
Trends in Colorectal Cancer Incidence Rates in the United States by Tumor Location and Stage, 1992–2008
Authors: Siegel Rebecca L. , Ward Elizabeth M. , Jemal Ahmedin 
Published: March 2012

Abstract
Background: Results from case–control studies outside the United States have been conflicted about the efficacy of colonoscopy for reducing cancer risk in the right colon. To contribute to this discourse from an alternative perspective, we analyzed high-quality surveillance data to report on recent trends in population-based colorectal cancer incidence rates by tumor location in the United States.
Methods: Data from cancer registries in the Surveillance, Epidemiology, and End Results Program were analyzed to examine colorectal cancer incidence trends from 1992 through 2008 among individuals aged ≥50 years (n = 267,072). Joinpoint regression analysis was used to quantify annual percent change in age-standardized rates by tumor location and disease stage.
Results: Incidence rates for right-sided colon tumors decreased annually by 2.6% (95% CI: 2.0–3.2) since 1999 in men and 2.3% (CI: 1.6–3.0) since 2000 in women, after remaining stable during the previous seven/eight years. Incidence rates for left-sided tumors were generally decreasing from 1992 to 2008 in both sexes. Beginning in 1999/2000, substantial, almost identical annual declines occurred for late-stage disease in both the right and left colon: 3.9% (CI: 3.1–4.8) and 4.2% (CI: 3.5–4.9), respectively, in men; and 3.3% (CI: 2.5–4.1) and 3.3% (CI: 2.8–3.8) in women.
Conclusion: Large declines in the incidence of right-sided colon tumors among individuals 50 years and older began around 2000.
Impact: Increased colonoscopy utilization during the past decade may have contributed to a reduction in risk for cancers in both the right and left colorectum in the United States. Cancer Epidemiol Biomarkers Prev; 21(3); 411–6. ©2012 AACR.
Nitrosamines and Heme Iron and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition
Authors: Jakszyn Paula G. , Allen Naomi E. , Lujan-Barroso Leila , Gonzalez Carlos A. , Key Timothy J. , Fonseca-Nunes Ana , Tjønneland Anne , Føns-Johnsen Nina , Overvad Kim , Teucher Birgit , Li Kuanrong , Boeing Heiner , Trichopoulou Antonia , Oikonomou Eleni , Sarantopoulou Maria , Saieva Calogero , Krogh Vittorio , Tumino Rosario , Ricceri Fulvio , Bueno-de-Mesquita H. Bas , Huerta José M. , Ardanaz Eva , Arguelles Marcial V. , Molina-Montes Esther , Larrañaga Nerea , Wirfält Elisabet , Wallström Peter , Johansson Mattias , Stattin Pär , Khaw Kay-Tee , Jenab Mazda , Fedirko Veronika , Riboli Elio 
Published: March 2012

Abstract
Background: The evidence about nitrosamines and heme iron intake and cancer risk is limited, despite the biologic plausibility of the hypothesis that these factors might increase cancer risk. We investigated the association between dietary nitrosamines and heme iron and the risk of prostate cancer among participants of European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods: Data on food consumption and complete follow-up for cancer occurrence was available for 139,005 men, recruited in 8 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, and study center, and adjusted for total energy intake, smoking status, marital status, dairy products, educational level, and body mass index.
Results: After a mean follow-up of 10 years, 4,606 participants were diagnosed with first incident prostate cancer. There was no overall association between prostate cancer risk and nitrosamines exposure (preformed and endogenous) or heme iron intake (HR for a doubling of intake: 1.00; 95% CI: 0.98–1.03 for N-Nitrosodimethlyamine, 0.95; 95% CI: 0.88–1.03 for endogenous Nitrosocompounds, and 1.00; 95 CI: 0.97–1.03 for heme iron).
Conclusions and Impact: Our findings do not support an effect of nitrosamines (endogenous and exogenous) and heme iron intake on prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 21(3); 547–51. ©2012 AACR.
Tobacco Addiction and The Risk of Upper Aerodigestive Tract Cancer in A Multicenter Case-Control Study
Authors: YC Lee , M Marron , S Benhamou , C Bouchardy , W Ahrens , H Pohlabeln , P Lagiou , D Trichopoulos , A Agudo , X Castellsague , V Bencko , I Holcatova , K Kjaerheim , F Merletti , L Richiardi , GJ Macfarlane , TV Macfarlane , R Talamini , L Barzan , C Canova , L Simonato , DI Conway , PA McKinney , P Thomson , A Znaor , CM Healy , BE McCartan , P Boffetta , P Brennan , M Hashibe 
Published: March 2012

Abstract
Background: While previous studies on tobacco and alcohol and the risk of upper aerodigestive tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and/or alcohol, studies on addiction to tobacco itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is a risk factor for UADT SCC risk in the multicenter case-control study (ARCAGE) in Western Europe independent of tobacco smoking or alcohol drinking intensity or duration.
Methods: The analyses included 1,905 ever smoking UADT SCC cases (871 oral cavity/oropharynx, 814 hypopharynx/larynx, 127 esophagus, and 93 overlapping oral cavity/pharynx) and 1,489 ever smoking controls. The addiction variables included first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden, and cigarettes per day. Odds ratios (OR) and 95% confidence intervals (95% CI) for UADT cancers with addiction variables were estimated with unconditional logistic regression, adjusting for center, age, sex, education level, alcohol consumption, and tobacco smoking.
Results: Among current smokers, 76.47% of cases were categorized in the highest addiction level, whereas 54.69% of controls were in that category. The participants who smoked their first cigarette within 5 minutes of waking up were two times more likely to develop UADT SCC (OR = 2.22, 95% CI 1.57–3.15) than those who smoked 60 minutes after waking up. A higher modified Fagerstram score, reflecting greater tobacco addiction, was associated with an increased risk of UADT SCC among current smokers, but not among former smokers.
Conclusion: We observed that time to first cigarette after waking up was associated with UADT SCC risk, regardless of heavy smoking or alcohol drinking behaviors. These results are consistent with residual effect of smoking that was not captured by the questionnaire responses alone.
An Affective Booster Moderates the Relationship Between Message Frame and Behavioral Intentions
Authors: RA Ferrer , WMP Klein , LE Zajac , SR Land , BS Ling 
Published: March 2012

Abstract
This study examined whether emotion moderates the degree to which framed messages influences colorectal cancer (CRC) screening intentions and self-efficacy for screening. Previous research has demonstrated that loss-framed messages are more effective than gain-framed messages in motivating detection behaviors such as screening. However, overall effects of framing in the context of health messages have been small and heterogeneous, highlighting the pressing need to identify moderators of framed message effectiveness. We paired a standard framing manipulation with an “affective booster” to increase anticipated and anticipatory emotions associated with the framed messages in a 2 × 2 (gain-loss by affective booster-no booster). The loss-framed message was paired with a complementary affective booster intended to facilitate worry and regret; the gain-framed message was paired with a complementary booster intended to facilitate relief. Consistent with previous research, we found that loss-framed messages were more effective in increasing intentions to screen for CRC (Î2 = -.38, t = -2.19, p = .03, d = 0.55). The inclusion of the affective booster had no overall effect on intentions to screen (Î2 = -.06, t = -0.39, p = .70, d = 0.10). However, we found a significant interaction (Î2 = .48, t = 2.13, p = .04, d = 0.53), such that among individuals who received gain-framed messages (but not loss-framed messages), the affective booster increased message persuasiveness. A similar pattern of results was uncovered with respect to self-efficacy for screening, where an affective booster increased self-efficacy among the gain-frame message recipients, bringing their self-efficacy in line with those who had received the loss-framed message. This study indicates that in the presence of affective boosters, loss-framed messages may lose their advantage over gain-framed messages in motivating detection behaviors.
Coronary Artery Bypass Graft
Authors: Hu Shengshou , Zheng Zhe , Yuan Xin , Wang Yun , Normand Sharon-Lise T. , Ross Joseph S. , Krumholz Harlan M. 
Published: March 2012

Background—
The use of coronary artery bypass grafting (CABG) surgery in China is growing, but little is known about hospital-level performance. We sought to characterize the variation in performance across hospitals participating in a national registry in China.

Methods and Results—
The study sample was drawn from the Chinese Cardiac Surgery Registry, a national multicenter database that includes 43 hospitals across 13 provinces and 4 direct-controlled municipalities in China. We assessed consecutive patients undergoing isolated CABG surgery during the period of January 1, 2007, through December 31, 2008. Hierarchical generalized linear models were used to estimate hospital-level risk-standardized in-hospital all-cause mortality rates (RSMR) and major complication rates (RSMCR), which included death, myocardial infarction, reoperation for bleeding, mediastinal infection, stroke, reintubation, and renal failure. Among 8739 patients who underwent isolated CABG surgery, the mean age was 62.2 years (SD=9.2), and 78% were male. Observed in-hospital mortality and complication rates were 2.2% (95% confidence interval [CI], 1.9–2.5%) and 6.6% (95% CI, 6.1–7.1%), respectively. The mean RSMR was 1.9% (SD=1.1), with a range of 0.7–5.8%, and the mean RSMCR was 6.4% (SD=1.5), with a range of 3.8–10.1%. The odds of dying and the odds of having a complication after CABG surgery at a hospital 1 SD below the average relative to a hospital 1 SD above the average were 2.06 (95% CI, 1.40–3.04) and 1.53 (95% CI, 1.31–1.79), respectively. The Eastern region had the lowest RSMR and RSMCR (1.6% and 5.8%, respectively), whereas the Central region had the highest RSMR (2.5%) and the Southern region had the highest RSMCR (7.7%).

Conclusions—
Mortality and complication rates after CABG surgery in the Chinese Cardiac Surgery Registry are generally low but vary by hospital and region within China. These results suggest that there are opportunities to improve outcomes in some CABG facilities.
Body Mass Index, Surgery, and Risk of Venous Thromboembolism in Middle-Aged Women
Authors: Parkin Lianne , Sweetland Siân , Balkwill Angela , Green Jane , Reeves Gillian , Beral Valerie 
Published: March 2012

Background—
Obesity and surgery are known risk factors for venous thromboembolism (VTE), but there is limited information about the independent effects of obesity on the incidence of postoperative VTE. We linked questionnaire data from the Million Women Study with hospital admission and death records to examine the risk of VTE in relation to body mass index (BMI) both in the absence of surgery and in the first 12 weeks following an operation.

Methods and Results—

Overall, 1 170 495 women (mean age, 56.1 years) recruited in 1996 to 2001 through the National Health Service Breast Screening Programme in England and Scotland were followed for an average of 6 years, during which time 6438 were admitted to hospital or died of VTE. The adjusted relative risks of VTE increased progressively with increasing BMI and women with a BMI ≥35 kg/m
2
were 3–4 times as likely to develop VTE as those with a BMI 22.5 to 24.9 (relative risk 3.45 [95% CI 3.09–3.86]). Overweight and obese women were more likely than lean women to be admitted for surgery and also to develop postoperative VTE. During a 12-week period without surgery, the incidence rates of VTE per 1000 women with a BMI <25 and ≥25 were 0.10 (0.09–0.10) and 0.19 (0.18–0.20); the corresponding rates in the 12 weeks following day and inpatient surgery were, respectively, about 4 and 40 times higher.

Conclusions—
VTE risk increases with increasing BMI and the associated excess risk is much greater after surgery than without surgery.