bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 838: Sugar-sweetened beverage intake and risk of early-onset colorectal cancer
Authors: Hur Jinhee , Otegbeye Ebunoluwa , Joh Hee-Kyung , Nimptsch Katharina , Ng Kimmie , Ogino Shuji , Meyerhardt Jeffrey A. , Chan Andrew T. , Willett Walter C. , Wu Kana , Giovannucci Edward , Cao Yin 
Published: July 2021

Abstract
Background: The incidence of early-onset colorectal cancer (EO-CRC) diagnosed under age 50 continues to rise, and the pattern shows a strong birth cohort effect. Sugar-sweetened beverage (SSB) consumption had substantially increased across successive birth cohorts until 2000, and the population under age 50 has the highest level of consumption. Despite the well-documented, adverse metabolic effects of SSBs, their link with EO-CRC remains unexamined.
Methods: In the Nurses' Health Study II, consisting of US female registered nurses aged 25-42 in 1989, we prospectively investigated the association between SSB intake and risk of EO-CRC. A total of 95,621 women who had reported beverage intake using validated food frequency questionnaires every 4 years since 1991 were followed up through June 2015. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% confidence intervals (CIs).
Results: We documented 109 EO-CRC cases over up to 24 years of follow-up (1,358,158 person-years). SSB consumption was associated with a higher risk of EO-CRC. Compared with individuals who consumed &lt;1 serving/week of SSBs, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR, 2.18; 95% CI, 1.10-4.35; P for trend=0.02). Each additional serving/day of SSB consumption was associated with a 16% higher risk of EO-CRC (RR, 1.16; 95% CI, 1.00-1.36). Replacing each serving/day of SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk, or total milk was associated with a 17-36% lower risk of EO-CRC.
Conclusion: Higher SSB intake was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.
Citation Format: Jinhee Hur, Ebunoluwa Otegbeye, Hee-Kyung Joh, Katharina Nimptsch, Kimmie Ng, Shuji Ogino, Jeffrey A. Meyerhardt, Andrew T. Chan, Walter C. Willett, Kana Wu, Edward Giovannucci, Yin Cao. Sugar-sweetened beverage intake and risk of early-onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 838.
Abstract 841: Risk of hepatobiliary & pancreatic cancer in inflammatory bowel disease
Authors: Yu Jingru , Refsum Erle , Helsingen Lise M. , Folseraas Trine , Ploner Alexander , Wieszczy Paulina , Barua Ishita , Jodal Henriette C. , Melum Espen , Løberg Magnus , Blom Johannes , Bretthauer Michael , Adami Hans-Olov , Kalager Mette , Ye Weimin 
Published: July 2021

Abstract
Background: The risk of hepatobiliary and pancreatic cancer in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC) has not been reliably quantified in large, prospective studies with long-term follow-up.
Methods: We performed a population cohort study of all patients diagnosed with IBD in Norway and Sweden from 1987 to 2015. Participants were followed through linkage to national cancer, cause of death and population registers. We calculated standardized incidence ratios (SIR) with 95% confidence intervals (CIs) and absolute risk of hepatobiliary and pancreatic cancer by PSC status and other clinical characteristics.
Results: We identified 141,960 IBD patients, 4,548 (3.2%) of these with concomitant PSC. During a median follow-up time of 10.0 years, we identified 479 biliary tract cancers (SIR 5.2, 95% CI 4.7-5.7), 127 hepatocellular carcinomas (SIR 2.1, 95% CI 1.8-2.5) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2-1.5). The relative risks were considerably higher in patients with PSC, with SIRs of 142 (95% CI 125-160) for biliary tract, 27.7 (95% CI 19.4-38.5) for hepatocellular, and 9.0 (95% CI 6.3-12.6) for pancreatic cancer. For IBD patients without PSC, we found SIRs of 2.5 (95% CI 2.2-2.9), 1.5 (1.2-1.8), and 1.2 (1.1-1.4) for biliary tract cancer, hepatocellular carcinoma, and pancreatic cancer, respectively.
Conclusion: Patients with IBD experience a substantially increased risk of biliary tract cancer. Although the risk is largely confined to patients with concomitant PSC, non-PSC patients also confer a moderate excess risk.
Citation Format: Jingru Yu, Erle Refsum, Lise M. Helsingen, Trine Folseraas, Alexander Ploner, Paulina Wieszczy, Ishita Barua, Henriette C. Jodal, Espen Melum, Magnus Løberg, Johannes Blom, Michael Bretthauer, Hans-Olov Adami, Mette Kalager, Weimin Ye. Risk of hepatobiliary & pancreatic cancer in inflammatory bowel disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 841.
Abstract 851: Associations of dietary calcium and magnesium intakes with lung cancer risk among low-income Americans: Results from the Southern Community Cohort Study
Authors: Yoon Hyung-Suk , Shu Xiao Ou , Cai Hui , Zheng Wei , Blot William J. , Cai Qiuyin 
Published: July 2021

Abstract
Background: Previous studies have suggested the potential roles of dietary intakes of calcium and magnesium in human cancer development, but little is known about their associations with lung cancer risk, especially among African Americans (AAs) and low-income populations.
Objectives: We conducted a nested case-control study to investigate the associations of dietary calcium and magnesium intakes with lung cancer risk among a low-income population of AAs and European Americans (EAs) in the Southeastern United States.
Methods: A total of 1,560 incident lung cancer cases who were diagnosed at least two years after enrollment and 5,926 matched controls from the Southern Community Cohort Study were included. Dietary calcium and magnesium intakes were assessed using a validated food frequency questionnaire at study enrollment. Multivariate logistic regression models were used to estimate odds ratios (ORs) and corresponding confidence intervals (95% CIs) for lung cancer risk associated with intakes of calcium and magnesium, and calcium/magnesium ratios after adjusting for enrollment age, education, smoking status, and pack-years, physical activity, alcohol drinking, household income, history of chronic obstructive pulmonary disease, body mass index, energy intake, and calcium or magnesium intake.
Results: Calcium intake was significantly associated with an increased risk of lung cancer among AAs but not among EAs; ORs (95% CI) for the highest compared with lowest quartiles were 1.56 (1.03-2.36) and 1.14 (0.68-1.92) for AAs and EAs, respectively (p for interaction: 0.03). Meanwhile, magnesium intake was significantly associated with a reduced risk of lung cancer risk among AAs but not among EAs; ORs (95% CI) for the highest compared with lowest quartiles were 0.55 (0.35-0.89) and 0.68 (0.39-1.18), respectively (p for interaction: 0.68). ORs (95% CI) for the highest compared with the lowest quartiles for calcium/magnesium ratios were 1.21 (0.96-1.53) for AAs and 1.17 (0.85-1.61) for EAs. These associations were more evident among men and never-smokers.
Conclusion: Our results suggest that higher dietary calcium and lower dietary magnesium intakes are associated with an increased risk of lung cancer, especially among AAs, raising the possibility that dietary factors may contribute to a higher risk of lung cancer among AA than EA men.
Citation Format: Hyung-Suk Yoon, Xiao Ou Shu, Hui Cai, Wei Zheng, William J. Blot, Qiuyin Cai. Associations of dietary calcium and magnesium intakes with lung cancer risk among low-income Americans: Results from the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 851.
Abstract 865: Genomic and evolutionary classification of lung cancer in never smokers from the Sherlock-Lung study
Authors: Zhang Tongwu , Alexandrov Ludmil B. , Zhao Wei , Sang Jian , Shi Jianxin , Zhu Bin , Gordenin Dmitry A. , Garcia-Closas Montserrat , Lan Qing , Rothman Nathaniel , Chanock Stephen J. , Wedge David C. , Landi Maria Teresa 
Published: July 2021

Abstract
Lung cancer in never smokers (LCINS) is a common cause of cancer mortality, but is poorly characterized. Here we show, through high coverage whole genome sequencing of 232 tumors/blood pairs, that LCINS can be separated into three subtypes, defined by somatic copy number aberrations. While the dominant subtype (‘piano'), rarely found in lung cancer from smokers, is characterized by quiet copy number profiles, the other subtypes are associated with specific arm-level amplifications and EGFR mutations (‘mezzo-forte'), and whole genome doubling (‘forte'). Piano tumors feature somatic UBA1 mutations, germline AR variants, and stem cell-like properties, including low mutational burden, infrequent TP53 alterations, high intra-tumor heterogeneity, long telomeres, and slow growth as suggested by the occurrence of cancer driver genes decades prior to tumor diagnosis. In contrast, driver mutations in mezzo-forte and forte tumors are generally late clonal events acquired close to tumor diagnosis, thus potentially facilitating target identification with a single biopsy. The mutational signature associated with direct exposure to tobacco smoking (SBS4) was not observed in our study, even in cases with reported exposure to second-hand tobacco smoke. No significant differences of mutational spectra were found between passive and non-passive smokers. While genes within the RTK-RAS pathway have distinct impacts on survival, mutations in TP53, CHEK2, EGFR, or loss of 15q or 22q independently doubled mortality. These genomic alterations in forte and mezzo-forte subtypes, and stem cell-like features in piano tumors create avenues for personalized therapeutic strategies in LCINS.
Citation Format: Tongwu Zhang, Ludmil B. Alexandrov, Wei Zhao, Jian Sang, Jianxin Shi, Bin Zhu, Dmitry A. Gordenin, Montserrat Garcia-Closas, Qing Lan, Nathaniel Rothman, Stephen J. Chanock, David C. Wedge, Maria Teresa Landi. Genomic and evolutionary classification of lung cancer in never smokers from the Sherlock-Lung study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 865.
Abstract 877: Use of beta blockers and death from breast cancer in New Zealand breast cancer patients
Authors: Scott Oliver William , TinTin Sandar , Cavadino Alana , Elwood Mark 
Published: July 2021

Abstract
Background Beta blockers (BB), used for a range of cardiovascular indications, have been associated with improved cancer outcomes in international studies. This study examines the association between the use of BBs and death from breast cancer in New Zealand women.
Methods Women who were diagnosed with breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to pharmaceutical data, hospital discharges, and death records. Median follow up time was 3.96 years. Cox proportional hazard models were used to assess the hazard of breast cancer specific death (BCD) associated with BB use.
Results Of the 14,971 women included in analysis, 21% used a BB after diagnosis. Although not significant, BB use increased the risk of BCD (adjusted hazard ratio: 1.15; 95% CI: 0.99-1.33). When considering subgroups however, the increased risk only remained in those with at least one cardiac condition, in patients under 80 years of age, and in those who were dispensed a BB in the last periods of life. When excluding dispensings in the six months prior to death/last follow up, the adjusted hazard ratio between BB use and BCD decreased to 0.95 (95% CI: 0.81-1.11). Risk was highest with short term use and decreased consistently with ever increasing doses.
Conclusions The initial increased risk is likely to be due to confounding by indication, and there was a suggestion of a protective effect of long-term BB use on BCD.
Citation Format: Oliver William Scott, Sandar TinTin, Alana Cavadino, Mark Elwood. Use of beta blockers and death from breast cancer in New Zealand breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 877.
Abstract 878: Contraceptive use and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers: A prospective cohort study
Authors: Xia Yue Yin , Lubinski Jan , Rosen Barry , Moller Pal , Eisen Andrea , Ainsworth Peter , Senter Leigha , Bordeleau Louise , Neuhausen Susan L. , Singer Christian F. , Brooks Jennifer , Sun Ping , Narod Steven A. , Kotsopoulos Joanne 
Published: July 2021

Abstract
Background: Oral contraceptive use is associated with a significantly reduced risk of ovarian cancer among BRCA1 and BRCA2 mutation carriers. To date, there have been no prospective analyses of this relationship, and the impact of other types of contraception (e.g. intrauterine device (IUD), implant, patch, injection) on BRCA-associated ovarian cancer risk is unknown. The goal of this study is to prospectively evaluate the relationship between types of contraception and ovarian cancer incidence in women with a BRCA1 or BRCA2 mutation.
Methods: The longitudinal study included 3,298 eligible BRCA1/2 mutation carriers. Self-reported information regarding contraceptive use, including medication name, start year, end year, duration of use and method of administration were collected by biennial questionnaire. Women were classified according to history of contraceptive use (ever/never), duration of use, contraceptive method, calendar year of initiation and time since last use. Time-dependent Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of ovarian cancer associated with each contraceptive method.
Results: There were 84 incident ovarian cancer cases diagnosed over a mean follow-up period of 5.1 years. There was no significant association between ever use of an IUD (HR: 0.78; 95% CI: 0.28-2.14) and risk of ovarian cancer compared to IUD never users. Ongoing analyses will focus on the relationships between other contraceptive methods, formulations and duration of use on ovarian cancer risk, further stratified by histology and site of origin.
Conclusions: Preliminary findings from this prospective analysis suggest that IUD use may not be protective among BRCA1/2 mutation carriers. Ongoing results will elucidate the impact of contraceptive formulation and method on ovarian cancer risk to inform clinical recommendations surrounding the use of contraceptive agents for chemoprevention in high risk women.
Citation Format: Yue Yin Xia, Jan Lubinski, Barry Rosen, Pal Moller, Andrea Eisen, Peter Ainsworth, Leigha Senter, Louise Bordeleau, Susan L. Neuhausen, Christian F. Singer, Jennifer Brooks, Ping Sun, Steven A. Narod, Joanne Kotsopoulos. Contraceptive use and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 878.
Abstract 880: Development and validation of an electronic health record-based absolute risk prediction model for esophageal cancer in the primary care setting in China
Authors: Han Yuting , Yu Canqing , Guo Yu , Pei Pei , Yang Ling , Chen Yiping , Du Huaidong , Chen Junshi , Chen Zhengming , Huo Dezheng , Lv Jun , Li Liming 
Published: July 2021

Abstract
Background This study aims to develop a set of electronic health record (EHR)-based absolute risk prediction models for esophageal cancer (EC), which are nationally applicable and easily integrated into the EHR system in China.
Methods The study used data from China Kadoorie Biobank (CKB), a large nationwide prospective cohort recruited during 2004-2008 in ten regions. In a random two-thirds of the 510,145 participants with no prior cancer diagnoses, we developed four nested models, according to the availability of predictors in EHRs. A flexible parametric survival model was fitted to calculate a 10-year absolute risk of EC accounting for the competing risk of mortality from other diseases. Besides discrimination and calibration, we estimated a range of performance indices (e.g. sensitivity and specificity) and compared the model performance with current screening criteria in the remaining one-third.
Results During a median of 11.1 years of follow-up, we observed 2,550 EC incident cases. The most sophisticated model included EHR variable (age, sex, region risk level [of ten regions: Hui county in Henan province and Pengzhou in Sichuan province], education level, family history of cancer, smoking, alcohol drinking, body mass index), and physical activity, hot tea consumption, and fresh fruit consumption. In the validation dataset, as more predictors included, the area under the receiver-operating characteristic curve statistically increased from 0.748 (0.732-0.763) to 0.883 (0.867-0.895). We observed a great agreement between predicted and observed risk, except for a slight underestimation in the top deciles. Taking 0.40% as the 10-year risk cut-off, models had sensitivities and specificities of around 80% and largely outperformed the current screening criteria.
Conclusions Based only on non-invasive predictors, even the model including only five predictors in the EHRs exhibited excellent calibration and discrimination. Utilizing limited predictors in EHRs, our models are useful to develop nationwide risk-stratified screening strategies for esophageal cancer.
Citation Format: Yuting Han, Canqing Yu, Yu Guo, Pei Pei, Ling Yang, Yiping Chen, Huaidong Du, Junshi Chen, Zhengming Chen, Dezheng Huo, Jun Lv, Liming Li. Development and validation of an electronic health record-based absolute risk prediction model for esophageal cancer in the primary care setting in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 880.
Abstract 886: Prediction of outcome in Li-Fraumeni Syndrome: Development of an integrative function-based prognostic model
Authors: Fischer Nicholas , Malkin David 
Published: July 2021

Abstract
Li-Fraumeni Syndrome (LFS) is a highly penetrant familial cancer disorder caused by germline TP53 mutations. Hundreds of different germline TP53 mutations with a wide gradient of functional consequences have been found in association with LFS, which has a remarkably diverse clinical spectrum in terms of tumor type, age of onset, penetrance, and survival rates. Clinical tools for prognostication and risk stratification are needed to guide clinical decision making. We performed an integrated analysis combining five large-scale mutant p53 functional screens to identify three functionally distinct groups of mutations. Combined functional scores measuring multiple parameters (loss-of-function, dominant negative activity, growth inhibition, oligomeric status, and transcriptional activity) were used to classify mutations as high, intermediate, or low pathogenicity. Patients identified with germline TP53 mutations at The Hospital for Sick Children and other institutes (174 patients from 50 families) provided the discovery set. An external validation cohort included 1674 patients from 1522 families with germline TP53 mutations collected from the International Agency for Research on Cancer database. Our mutation classifications stratified carriers into three distinct risk groups with significantly different overall survival outcomes in the discovery (P=0.02) and validation cohorts (P&lt;0.0001). In the discovery dataset, patients in the high-risk group had considerably shorter median life expectancy (28 years; n=21) compared to the intermediate-risk group (61 years; n=51) and low-risk group (median survival not reached; n=10). On average, 92% (24/26) of patients in the high-risk group developed tumors compared to only 63% (32/51) in the low-risk group (P=0.005). This model remained significant when applied to the validation cohort. In conclusion, patients at increased risk of cancer mortality can be identified to guide treatment and cancer surveillance strategies.
Citation Format: Nicholas Fischer, David Malkin. Prediction of outcome in Li-Fraumeni Syndrome: Development of an integrative function-based prognostic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 886.
Abstract 912: CLDN6 and CLDN9 dual targeting antibody drug conjugates for the treatment of ovarian and endometrial cancers
Authors: Du Liang , Zhang Hongyan , Jin Lina , Chen Yali , Wan Tingting , Xu Liuliu 
Published: July 2021

Abstract
Claudins (CLDNs) are tight junction proteins that regulate epithelial-cell barrier function and polarity. Up-regulation of certain CLDN proteins has been associated with the malignant phenotype. Embryonic, stem-cell specific CLDN6 is absent in normal adult tissues. Our in-house data showed that it is highly expressed in serous ovarian (66% cases showed 2+/3+/4+ expression of CLDN6), and testis cancers (100% cases showed 4+ expression of CLDN6) in Chinese population, and is an “ideal” target in these cancer types. CLDN9, sharing high homology with CLDN6 exhibits similar distribution patterns with CLDN6, like the absence in normal tissues and up-regulation in ovarian and endometrial cancer. We propose to simultaneously target both CLDN6 and CLDN9 for treatment of ovarian cancer and endometrial cancer to achieve better anti-tumor efficacy and expand the treatment to a larger population of patients. To this end, we designed a high-through-put antibody screening process and discovered two antibodies GB7008-03 and GB7008-05, both of which binds CLDN6 and CLDN9 with high affinity, while sparing other CLDN members. Both candidates demonstrated superior antibody-mediated antigen internalization than ASP1650, the forerunner in clinical trials. GB7008-03 and GB7008-05 also showed good ADCC potency on CLDN6 expressing tumor cell lines. Currently we are developing antibody-drug-conjugates based on these two antibodies. In vivo efficacy of these ADCs in CDX models will be presented.
Citation Format: Liang Du, Hongyan Zhang, Lina Jin, Yali Chen, Tingting Wan, Liuliu Xu. CLDN6 and CLDN9 dual targeting antibody drug conjugates for the treatment of ovarian and endometrial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 912.