bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 793: Potential impact of time trend of lifestyle factors on burden of gastrointestinal cancer in China
Authors: Wu You , Li Yanping , Giovannucci Edward , Hu Frank B. 
Published: July 2021

Abstract
BACKGROUND: Colorectal, esophageal, stomach, and liver cancers are four major gastrointestinal (GI) cancers that have 2-3 times the age-standardized incidence rates in China compared to the global average. Examining the time trend of risk factors associated with GI cancer would help us project the future trend of GI cancer incidence in China and guide public health policymaking.
METHODS: We estimated the time trend of relevant dietary and lifestyle factors in China based on data from the China Health and Nutrition Survey 1991-2011. We applied the comparative risk assessment method to estimate the population attributable fraction (PAF%) and the absolute number of GI cancer events attributable to all non-optimal levels of each risk factor. We have also projected the lifestyle factors and the estimated burden of GI cancer in the next 30 years.
RESULTS: In 2011, the overall estimated PAF% by all risk factors under study is 73% for esophageal cancer, 59% for colorectal cancer, 47% for gastric cancer, and 35% for liver cancer. Smoking, low fruit intake, high red meat consumption, high body mass index (BMI), and high alcohol consumption were the top 5 contributors to GI cancer incidence in China; each accounted for 173, 134, 132, 125, and 91 thousand GI cancer cases, respectively. For specific cancer sites, high red meat consumption accounted for the most cases of colorectal cancer in 2011 (N = 51,405; PAF% = 19%) and is projected to have higher PAF% from 15% in 1997 to 23% in 2041. High BMI is responsible for the most liver cancer cases in 2011 (N = 55,244; PAF% = 17%) and has an increasing trend in expected PAF% from 7% in 1991 to 20% in 2041; low fruit intake is the top contributor for esophageal cancer in 2011 (N = 85,345; PAR% = 29%) with a downward trend in the next few decades (PAF% from 33% in 1997 to 23% in 2041); high sodium intake represented the highest PAF% for gastric cancer in 2011 (68,858 cases, PAF% = 17%), but is expected to be overpassed by smoking, high BMI, and red meat consumption in 2015-2025.
CONCLUSIONS: China has witnessed significant transitions in lifestyle, including diet, physical activity, and obesity. The impact of the lifestyle risk factors on the risk of GI cancer has been increasing from 1991 to 2011 and is projected to continue growing. High red meat consumption and high BMI call for extra attention as they are among the top contributors to GI cancer and are expected to have stronger impacts in the next 30 years in China.
Citation Format: You Wu, Yanping Li, Edward Giovannucci, Frank B. Hu. Potential impact of time trend of lifestyle factors on burden of gastrointestinal cancer 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 793.
Abstract 796: Investigating incidence and survival patterns of cutaneous malignant melanoma in the United States from 2006-2017
Authors: Kye Yae , Alvarado Luis , Dwivedi Alok , Chacon Jessica 
Published: July 2021

Abstract
Introduction: Skin cancers are one of the most common cancers in the United States with melanoma being the fifth leading cause of cancer. Despite its increasing incidence, there are limited studies on how skin cancer affects different races and ethnicities. Here, we conduct a population-based registry study to derive incidence and survival patterns of cutaneous malignant melanoma (CMM) in the US from 2006-2017. 17 population-based cancer registries from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. A total of 58,666 cases with histologically confirmed cases of cutaneous malignant melanoma were evaluated. Surprisingly, the CMM subtype that was predominantly found in the non-Hispanic whites (56%) and Hispanic whites (45%) was acral lentiginous melanoma, while “other” melanomas were predominant in the Asian (54%) and Black (77%) populations. Superficial spreading and lentigo maligna melanomas presented more commonly in men (69% and 63%). In addition, nodular and lentigo maligna melanomas had the poorest survival rates and had a median survival of 26 and 21 months.
Methods: The Surveillance, Epidemiology, and End Results Program (SEER) of the National Cancer Institute was used to calculate the incidence, proportion, and survival data. 58,66 histologically confirmed CMM cases reported by the 17 cancer registries from 2006-2017 were used. The 17 registries include 14 states (Alaska, greater and California, Connecticut, Georgia, Hawaii, Idaho, Iowa, Kentucky, Louisiana, Massachusetts, New Mexico, New York, Utah, Washington) and 4 standard metropolitan areas (Los Angeles, San Francisco-Oakland, and San Jose-Monterey, California; and Seattle-Puget Sound, Washington). Cases of the 4 major CMM subtypes as well as the “other” subtypes were identified using the World Health Organization's International Classification of Diseases for Oncology (ICD-0-3) morphology code.
Conclusion and future direction: CMM has been steadily increasing in incidence within the US. Moreover, the incidence rate of CMM in the Hispanic population has been rising. It is important that we continue to assess the epidemiological characteristics and trends of CMM subtypes in the US and increase awareness of skin cancer and its preventative measures in the Hispanic population. In addition, future studies should analyze the genetic and environmental factors that may be contributing to observed incidence rates in the Hispanic population.
Citation Format: Yae Kye, Luis Alvarado, Alok Dwivedi, Jessica Chacon. Investigating incidence and survival patterns of cutaneous malignant melanoma in the United States from 2006-2017 [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 796.
Abstract 799: Reduced diversity of HLA class II alleles may contribute to the early manifestation of breast cancer in BRCA1 mutation carriers
Authors: ShKuligina Ekaterina , Romanko Alexandr A. , Jankevic Tatjana , Martianov Aleksandr S. , Sokolova Tatyana N. , Ivantsov Alexandr O. , Imyanitov Evgeny N. 
Published: July 2021

Abstract
Female carriers of germline BRCA1 mutation almost inevitably develop breast cancer (BC). However, the age of BRCA1-associated cancer onset varies widely. We hypothesize that age-related penetrance of BRCA1 mutations may depend on the inherited variability in the host immune system. We utilized high-throughput HLA-typing to describe 10 classical HLA class I/II loci for 90 young (&lt;38 y.o.) and 73 elderly (&gt;57 y.o.) BRCA1-mutated BC patients. 39% of young females were homozygous for two or more HLA-II loci; this was significantly higher than in the “elderly” cohort [OR = 3.23; p = 0.002]. In contrast, women who harboured identical alleles at HLA-B locus (class I) had increased chances to stay tumour-free to their older ages [OR = 3.02; p = 0.077]. Allele HLA-DBR1*11:03/04 was overtly overrepresented in elderly BRCA1-driven BC [11% vs. 3%, p = 0.006]. The frequencies of HLA-DRB1*01:01 and HLA-DQB1*05 were significantly higher in group of “young” patients [p = 0.020 and p = 0.011, correspondently]. The tumour immunogenicity was analyzed in early-onset and late-onset BC patients through the evaluation of the intratumoral density of cytotoxic T-lymphocytes (TILs) with anti-CD8 IHC staining. 5/10 carcinomas arisen in young BRCA1-carriers were classified as a “hot” phenotype with a high density of TILs across the tumour. Inversely, the BC developed in “elderly” women was characterized by the reduced levels of TILs. Conclusions: 1) the limited repertoire of HLA peptides caused by the homozygosity for HLA II loci may increase susceptibility to BC in BRCA1-carriers and manifest by early disease onset; 2) tumours from “elderly” BRCA1-associated patients have reduced levels of lymphocytic infiltration compared to “young” patients. The research is supported by RSF grant #19-15-00207
Citation Format: Ekaterina ShKuligina, Alexandr A. Romanko, Tatjana Jankevic, Aleksandr S. Martianov, Tatyana N. Sokolova, Alexandr O. Ivantsov, Evgeny N. Imyanitov. Reduced diversity of HLA class II alleles may contribute to the early manifestation of breast cancer in BRCA1 mutation carriers [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 799.
Abstract 802: Multi-cancer profiles in high-risk CLL families
Authors: Harris Nathan Scott 
Published: July 2021

Abstract
Discovery of novel etiological factors for B-cell malignancies is hindered by the heterogeneity of these diseases. The identification of important multi-cancer profiles provides a new avenue for discovery, but requires novel approaches and specific resources. The Utah Population Database (UPDB) includes extensive genealogy for 5 million Utahns (from three to 18 generations). The UPDB also includes over 360,000 cancer diagnoses from the NCI SEER Utah Cancer Registry, making it a unique and ideal resource for analyzing cancer patterns in families. Here we performed a multi-cancer clustering approach to identify patterns of familial clustering of cancers in high-risk CLL families. Other cancers considered in the cancer profiles were: Hodgkins lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, multiple myeloma and 25 solid tumors. High risk CLL pedigrees were extracted from the UPDB. Based on cancer rates in UPDB, standardized incidence ratios were calculated for each pedigree for each of the 29 cancers. These vectors of cancer risks per pedigree were used as the basis for k-mediods clustering of the high-risk CLL families. Resulting clusters of families share similar co-aggregations of other B-cell malignancies and solid tumors. High-risk CLL families with similar multi-cancer profiles may be more etiologically homogeneous and provide improved power for the identification of underlying risk factors.
Citation Format: Nathan Scott Harris. Multi-cancer profiles in high-risk CLL families [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 802.
Abstract 805: A germline mutation of gene ATM p.C1899* is associated with a family history of multiple cancers in a family in Yunnan province, China
Authors: Sun Xianghua , Zhang Hushan , Zhang Wanfu , Zhang Zhiping , Li Bo 
Published: July 2021

Abstract
Background: Ataxia-telangiectasia mutated (ATM) is a gene that plays role in cell cycle checkpoints and DNA damage response, heterozygous germline mutations in ATM are considered as one of risk factor of breast cancer (BC). There are also some reports that ATM mutations are related to other tumor types, such as prostate cancer. Several pathogenic germline mutations in ATM have been reported included missense mutations, nonsense mutations, frameshift deletions, in-frame deletion, large deletion. Here, we report a family history of multiple cancers related to germline mutation of ATM p.C1899* in a family in Yunnan province, China.
Methods: The proband is a 58-year old male patient with colon cancer. Both tumor tissue samples and peripheral blood sample of the proband was subjected to next generation sequencing (NGS) analysis by 3D Medicines Inc., Shanghai, China, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). A novel germ-line mutation was identified, that was heterozygous ATM p.C1899* mutation (c.5697C&gt;A). Peripheral blood sample of other family members have been collected and send to 3D Medicines Inc., for NGS analysis.
Results: In total of 6 members of the family underwent NGS analysis, results showed that these members were carry a germline mutation of gene ATM p.C1899*, one uncle was patient with gastric cancer, and one aunt was patient with pancreatic cancer, which means this germline mutation was related with three different cancer in a family.
Conclusion: The mutation of ATM, especially germline mutation, may associated with multiple cancers, such as gastric cancer, colorectal cancer and pancreatic cancer. Accurate genetic testing should be given more attention to better control the risk of familial cancer.
Citation Format: Xianghua Sun, Hushan Zhang, Wanfu Zhang, Zhiping Zhang, Bo Li. A germline mutation of gene ATM p.C1899* is associated with a family history of multiple cancers in a family in Yunnan province, 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 805.
Abstract 81: Trop2 regulates prostate cancer growth and metastasis through distinct molecular mechanisms
Authors: Stoyanova Tanya Ivanova , Hsu En-Chi , Liu Shiqin , Marques Fernando Jose Garcia , Bermudez Abel , Aslan Merve , Shen Michelle , Pitteri Sharon , Brooks James D. 
Published: July 2021

Abstract
Background: The first line of treatment for men with advanced prostate cancer is androgen deprivation therapy. Although initial responses are observed, prostate cancer commonly relapses in its lethal metastatic form referred to as castration resistant prostate cancer (CRPC) with 1-2 years mean survival time. Neuroendocrine prostate cancer (NEPC) is highly aggressive, AR independent subtype and usually emerges post castration resistance. We recently identified that the cell surface receptor, Trop2, is a new driver of NEPC. Moreover, we demonstrated that Trop2 regulates prostate cancer growth and metastasis. In this study, we set out to delineate the molecular mechanisms through which Trop2 regulates prostate cancer growth and metastasis.
Methods: Proximity-dependent Biotin Identification (BioID) followed by mass spectrometry was performed to identify Trop2 interactome. Lentiviral infection was used to generate prostate cancer cell lines with over-expression of Trop2 and knock-down of NOTCH1, SLC4A7, PLEC, and OCLN shRNA to modulate gene expression levels. In vitro functional assays were performed including colony formation, and Matrigel drop 3D cell invasion assays.
Results: The Trop2 membrane interactome was identified utilizing Proximity-dependent Biotin Identification (BioID) in living cells and uncovered that Trop2-mediated prostate cancer growth and metastasis are orchestrated by distinct downstream pathways including Notch signaling (NOTCH1), control of intracellular pH (SLC4A7), exosome secretion (PLEC), and tight junctions (OCLN). Interaction of Trop2 binding partners including NOTCH1, SLC4A7, PLEC and OCLN with Trop2 were further validated by fluorescence resonance energy transfer (FRET) using confocal microscopy. Moreover, knocking down the Trop2 interacting partners in Trop2 over-expressing prostate cancer cells suppressed Trop2-driven growth and invasion ability.
Conclusions: In a previous study, we identified cell surface receptor, Trop2, as a novel driver of metastatic NEPC. Herein, our new findings reveal that Trop2 interacts with NOTCH1, SLC4A7, PLEC, and OCLN, which may highlight novel biological functions of Trop2 in prostate tumorigenesis and provide new understanding of the potential mechanism of neuroendocrine differentiation and metastasis to provide new therapeutic strategy for metastatic CRPC with neuroendocrine features.
Citation Format: Tanya Ivanova Stoyanova, En-Chi Hsu, Shiqin Liu, Fernando Jose Garcia Marques, Abel Bermudez, Merve Aslan, Michelle Shen, Sharon Pitteri, James D. Brooks. Trop2 regulates prostate cancer growth and metastasis through distinct molecular mechanisms [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 81.
Abstract 817: Probing the diabetes - colorectal cancer link using gene - environment interaction analyses
Authors: Dimou Niki , Kim Andre E. , Flanagan Orlagh , Murphy Neil , Bouras Emmanouil , Campbell Peter T. , Casey Graham , Gallinger Steven , Gruber Stephen B. , Hsu Li , Jenkins Mark A. , Lin Yi , Moreno Victor , Qu Conghui , Ruiz-Narvaez Edward , Stern Mariana C. , Tian Yu , Tsilidis Kostas , Gauderman W. James , Gunter Marc J. , Peters Ulrike 
Published: July 2021

Abstract
Background: Type 2 diabetes mellitus (T2D) is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship are unclear and it is not known if the association is modified by genetic variants. To provide insights into the molecular pathways potentially linking diabetes and colorectal cancer, we undertook a large-scale gene-environment interaction analysis (GxE).
Methods: We tested multiplicative statistical interactions between approximately 7 million common (allele frequency &gt;1%) genetic variants and T2D status in 31,529 colorectal cancer cases and 42,861 controls of European ancestry from 3 genetic consortia (GECCO/CCFR/CORECT). Statistical methods included traditional case-control logistic regression, case-only analyses, joint tests (2df/3df), and two-step approaches. We also explored additive and multiplicative interactions between polygenic risk score (PRS) of the known genome-wide significant loci for colorectal cancer and T2D. Results: Overall, T2D was positively associated with colorectal cancer risk [odds ratio [OR]: 1.25 (95% confidence interval [CI]: 1.14-1.36)]. A statistically significant interaction was identified between T2D status and an intronic variant in LRCH1 (rs9526201) and colorectal cancer risk using the 2-d.f. joint test (p-value:1.44x10-8). A statistically significant additive scale interaction between PRS for colorectal cancer and T2D was found (p-value: 1.8x10-10) such that the observed risk of developing colorectal cancer for individuals with T2D and a 1 standard deviation (SD) higher increment of PRS compared to non-diabetics with the lowest PRS was 0.184 more than if there was no interaction between T2D and PRS. Conclusion: These results suggest that variation in a gene related to immune function may modify the association of T2D with colorectal cancer and potentially provide novel insights into the biology underlying this relationship. Furthermore, our data show that genetic risk prediction models for CRC may need to consider non-genetic risk factors.
Citation Format: Niki Dimou, Andre E. Kim, Orlagh Flanagan, Neil Murphy, Emmanouil Bouras, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Li Hsu, Mark A. Jenkins, Yi Lin, Victor Moreno, Conghui Qu, Edward Ruiz-Narvaez, Mariana C. Stern, Yu Tian, Kostas Tsilidis, W. James Gauderman, Marc J. Gunter, Ulrike Peters. Probing the diabetes - colorectal cancer link using gene - environment interaction analyses [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 817.
Abstract 828: Common genetic variants influence the composition of the tumor immune microenvironment and host anti-tumor responses
Authors: Pagadala Meghana , Kim Hyo , Castro Andrea , Gonzalez-Colin Cristian , Wu Victoria , Cao Steven , Schmiedel Benjamin , Salem Rany , Gutkind Silvio , Thompson Wes , Pandurangan Vijayanand , Carter Hannah 
Published: July 2021

Abstract
Developing effective therapies to intervene in the tumor immune evasion process is a challenge further complicated by interindividual variability in tumor-host immunological interactions. Germline variation is a major component of interindividual variability usually studied by large-scale genome-wide association studies (GWAS) in the context of disease risk; yet, there is still a gap in our understanding of germline variation specifically in the tumor immune microenvironment. To address this, we systematically characterized the immune effects of germline genetic polymorphisms across 33 human cancer types in the TCGA. Immune microenvironment phenotypes include immune infiltration levels as calculated by CIBERSORTx and expression of immunomodulator genes obtained through literature curation. PCA analysis reduced dimensionality of immune phenotypes, with macrophage regulation and EP300/Proteosome expression mediating most variability amongst individuals. We identified 482 SNP-immune gene associations, where a subset of SNPs affected multiple immune phenotypes. Using cell-type and epigenetic analyses, we further characterized immune microenvironment variants to act through macrophage and dendritic cell-specific manners and alter immune-cell specific epigenetic regions. Through burden analysis, we found several of these variants interact to have stronger immune microenvironment effects. Lastly, using ICB-trial cohorts, we found several variants affecting LILRB2, LILRB4, LAIR1, CCBL2, and CTSW modulate response to immune checkpoint blockade. Our results provide better understanding of how germline variation modifies tumor immune microenvironment dynamics and will set up further studies to identify predictive biomarkers of the tumor immune microenvironment.
Citation Format: Meghana Pagadala, Hyo Kim, Andrea Castro, Cristian Gonzalez-Colin, Victoria Wu, Steven Cao, Benjamin Schmiedel, Rany Salem, Silvio Gutkind, Wes Thompson, Vijayanand Pandurangan, Hannah Carter. Common genetic variants influence the composition of the tumor immune microenvironment and host anti-tumor responses [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 828.