1,169 results on '"Freedman, Neal D."'
Search Results
2. Altered salivary microbiota associated with high-sugar beverage consumption
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Fan, Xiaozhou, Monson, Kelsey R., Peters, Brandilyn A., Whittington, Jennifer M., Um, Caroline Y., Oberstein, Paul E., McCullough, Marjorie L., Freedman, Neal D., Huang, Wen-Yi, Ahn, Jiyoung, and Hayes, Richard B.
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- 2024
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3. Genetically adjusted PSA levels for prostate cancer screening.
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Kachuri, Linda, Hoffmann, Thomas J, Jiang, Yu, Berndt, Sonja I, Shelley, John P, Schaffer, Kerry R, Machiela, Mitchell J, Freedman, Neal D, Huang, Wen-Yi, Li, Shengchao A, Easterlin, Ryder, Goodman, Phyllis J, Till, Cathee, Thompson, Ian, Lilja, Hans, Van Den Eeden, Stephen K, Chanock, Stephen J, Haiman, Christopher A, Conti, David V, Klein, Robert J, Mosley, Jonathan D, Graff, Rebecca E, and Witte, John S
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Humans ,Prostatic Neoplasms ,Prostate-Specific Antigen ,Biopsy ,Male ,Early Detection of Cancer ,Neoplasm Grading ,Aging ,Prevention ,Cancer ,Urologic Diseases ,Prostate Cancer ,Genetics ,Good Health and Well Being ,Medical and Health Sciences ,Immunology - Abstract
Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P
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- 2023
4. Moving towards FAIR practices in epidemiological research
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Garcia-Closas, Montserrat, Ahearn, Thomas U., Gaudet, Mia M., Hurson, Amber N., Balasubramanian, Jeya Balaji, Choudhury, Parichoy Pal, Gerlanc, Nicole M., Patel, Bhaumik, Russ, Daniel, Abubakar, Mustapha, Freedman, Neal D., Wong, Wendy S. W., Chanock, Stephen J., de Gonzalez, Amy Berrington, and Almeida, Jonas S
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Quantitative Biology - Populations and Evolution - Abstract
Reproducibility and replicability of research findings are central to the scientific integrity of epidemiology. In addition, many research questions require combiningdata from multiple sources to achieve adequate statistical power. However, barriers related to confidentiality, costs, and incentives often limit the extent and speed of sharing resources, both data and code. Epidemiological practices that follow FAIR principles can address these barriers by making resources (F)indable with the necessary metadata , (A)ccessible to authorized users and (I)nteroperable with other data, to optimize the (R)e-use of resources with appropriate credit to its creators. We provide an overview of these principles and describe approaches for implementation in epidemiology. Increasing degrees of FAIRness can be achieved by moving data and code from on-site locations to the Cloud, using machine-readable and non-proprietary files, and developing open-source code. Adoption of these practices will improve daily work and collaborative analyses, and facilitate compliance with data sharing policies from funders and scientific journals. Achieving a high degree of FAIRness will require funding, training, organizational support, recognition, and incentives for sharing resources. But these costs are amply outweighed by the benefits of making research more reproducible, impactful, and equitable by facilitating the re-use of precious research resources by the scientific community.
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- 2022
5. Inflated expectations: Rare-variant association analysis using public controls
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Kim, Jung, Karyadi, Danielle M, Hartley, Stephen W, Zhu, Bin, Wang, Mingyi, Wu, Dongjing, Song, Lei, Armstrong, Gregory T, Bhatia, Smita, Robison, Leslie L, Yasui, Yutaka, Carter, Brian, Sampson, Joshua N, Freedman, Neal D, Goldstein, Alisa M, Mirabello, Lisa, Chanock, Stephen J, Morton, Lindsay M, Savage, Sharon A, and Stewart, Douglas R
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Motivation ,High-Throughput Nucleotide Sequencing ,Polymorphism ,Single Nucleotide ,Software ,General Science & Technology - Abstract
The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.1 and several datasets sequenced in our laboratory to systematically investigate factors that could contribute to the false-positive discovery, as measured by λΔ95, a measure to quantify the degree of inflation in statistical significance. Analyses of datasets in this investigation found that 1) the significantly inflated distribution of test statistics decreased substantially when the same variant caller and filtering pipelines were employed, 2) differences in library prep kits and sequencers did not affect the false-positive discovery rate and, 3) joint vs. separate variant-calling of cases and controls did not contribute to the inflation of test statistics. Currently available methods do not adequately adjust for the high false-positive discovery. These results, especially if replicated, emphasize the risks of using public controls for rare-variant association tests in which individual-level data and the computational pipeline are not readily accessible, which prevents the use of the same variant-calling and filtering pipelines on both cases and controls. A plausible solution exists with the emergence of cloud-based computing, which can make it possible to bring containerized analytical pipelines to the data (rather than the data to the pipeline) and could avert or minimize these issues. It is suggested that future reports account for this issue and provide this as a limitation in reporting new findings based on studies that cannot practically analyze all data on a single pipeline.
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- 2023
6. Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma
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Purdue, Mark P., Dutta, Diptavo, Machiela, Mitchell J., Gorman, Bryan R., Winter, Timothy, Okuhara, Dayne, Cleland, Sara, Ferreiro-Iglesias, Aida, Scheet, Paul, Liu, Aoxing, Wu, Chao, Antwi, Samuel O., Larkin, James, Zequi, Stênio C., Sun, Maxine, Hikino, Keiko, Hajiran, Ali, Lawson, Keith A., Cárcano, Flavio, Blanchet, Odile, Shuch, Brian, Nepple, Kenneth G., Margue, Gaëlle, Sundi, Debasish, Diver, W. Ryan, Folgueira, Maria A.A.K., van Bokhoven, Adrie, Neffa, Florencia, Brown, Kevin M., Hofmann, Jonathan N., Rhee, Jongeun, Yeager, Meredith, Cole, Nathan R., Hicks, Belynda D., Manning, Michelle R., Hutchinson, Amy A., Rothman, Nathaniel, Huang, Wen-Yi, Linehan, W. Marston, Lori, Adriana, Ferragu, Matthieu, Zidane-Marinnes, Merzouka, Serrano, Sérgio, Magnabosco, Wesley J., BioBank Japan Project Consortium, Vilas, Ana, Decia, Ricardo, Carusso, Florencia, Graham, Laura S., Anderson, Kyra, Bilen, Mehmet A., Arciero, Cletus, Pellegrin, Isabelle, Ricard, Solène, FinnGen, Scelo, Ghislaine, Banks, Rosamonde E., Vasudev, Naveen S., Soomro, Naeem, Stewart, Grant D., Adeyoju, Adebanji, Bromage, Stephen, Hrouda, David, Gibbons, Norma, Patel, Poulam, Sullivan, Mark, Protheroe, Andrew, Nugent, Francesca I., Fournier, Michelle J., Zhang, Xiaoyu, Martin, Lisa J., Komisarenko, Maria, Eisen, Timothy, Cunningham, Sonia A., Connolly, Denise C., Uzzo, Robert G., Zaridze, David, Mukeria, Anush, Holcatova, Ivana, Hornakova, Anna, Foretova, Lenka, Janout, Vladimir, Mates, Dana, Jinga, Viorel, Rascu, Stefan, Mijuskovic, Mirjana, Savic, Slavisa, Milosavljevic, Sasa, Gaborieau, Valérie, Abedi-Ardekani, Behnoush, McKay, James, Johansson, Mattias, Phouthavongsy, Larry, Hayman, Lindsay, Li, Jason, Lungu, Ilinca, Bezerra, Stephania M., de Souza, Aline G., Sares, Claudia T.G., Reis, Rodolfo B., Gallucci, Fabio P., Cordeiro, Mauricio D., Pomerantz, Mark, Lee, Gwo-Shu M., Freedman, Matthew L., Jeong, Anhyo, Greenberg, Samantha E., Sanchez, Alejandro, Thompson, R. Houston, Sharma, Vidit, Thiel, David D., Ball, Colleen T., Abreu, Diego, Lam, Elaine T., Nahas, William C., Master, Viraj A., Patel, Alpa V., Bernhard, Jean-Christophe, Freedman, Neal D., Bigot, Pierre, Reis, Rui M., Colli, Leandro M., Finelli, Antonio, Manley, Brandon J., Terao, Chikashi, Choueiri, Toni K., Carraro, Dirce M., Houlston, Richard, Eckel-Passow, Jeanette E., Abbosh, Philip H., Ganna, Andrea, Brennan, Paul, Gu, Jian, Chanock, Stephen J., Guo, Xinyu, Winter, Timothy D., Jahagirdar, Om, Ha, Eunji, and Susztak, Katalin
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- 2024
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7. Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study
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Nalini, Mahdi, Poustchi, Hossein, Bhandari, Deepak, Chang, Cindy M., Blount, Benjamin C., Wang, Lanqing, Feng, Jun, Gross, Amy, Khoshnia, Masoud, Pourshams, Akram, Sotoudeh, Masoud, Gail, Mitchell H., Graubard, Barry I., Dawsey, Sanford M, Kamangar, Farin, Boffetta, Paolo, Brennan, Paul, Abnet, Christian C., Malekzadeh, Reza, Freedman, Neal D., and Etemadi, Arash
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- 2024
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8. Transcriptome-wide association analysis identifies candidate susceptibility genes for prostate-specific antigen levels in men without prostate cancer
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Chen, Dorothy M., Dong, Ruocheng, Kachuri, Linda, Hoffmann, Thomas J., Jiang, Yu, Berndt, Sonja I., Shelley, John P., Schaffer, Kerry R., Machiela, Mitchell J., Freedman, Neal D., Huang, Wen-Yi, Li, Shengchao A., Lilja, Hans, Justice, Amy C., Madduri, Ravi K., Rodriguez, Alex A., Van Den Eeden, Stephen K., Chanock, Stephen J., Haiman, Christopher A., Conti, David V., Klein, Robert J., Mosley, Jonathan D., Witte, John S., and Graff, Rebecca E.
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- 2024
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9. The landscape of rare genetic variants in familial Waldenström macroglobulinemia
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Pemov, Alexander, Kim, Jung, Luo, Wen, Liu, Jia, Graham, Cole, Jones, Kristine, DeMangel, Delphine, Freedman, Neal D., Dumontet, Charles, Zhu, Bin, McMaster, Mary L., and Stewart, Douglas R.
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- 2024
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10. Prevalence and determinants of opioid use disorder among long-term opiate users in Golestan Cohort Study
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Alvand, Saba, Amin-Esmaeili, Masoumeh, Poustchi, Hossein, Roshandel, Gholamreza, Sadeghi, Yasaman, Sharifi, Vandad, Kamangar, Farin, Dawsey, Sanford M., Freedman, Neal D., Abnet, Christian C., Rahimi-Movaghar, Afarin, Malekzadeh, Reza, and Etemadi, Arash
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- 2023
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11. Quest markup for developing FAIR questionnaire modules for epidemiologic studies
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Russ, Daniel E., Gerlanc, Nicole M., Shen, Brian, Patel, Bhaumik, de González, Amy Berrington, Freedman, Neal D., Cusack, Julie M., Gaudet, Mia M., García-Closas, Montserrat, and Almeida, Jonas S.
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- 2023
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12. A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
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Midttun, Øivind, Ulvik, Arve, Meyer, Klaus, Zahed, Hana, Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Behndig, Annelie F., Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loïc, Weinstein, Stephanie J., Cai, Qiuyin, Arslan, Alan A., Chen, Yu, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Robbins, Hilary A., Brennan, Paul, Johansson, Mattias, and Ueland, Per M.
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- 2023
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13. GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas
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Machiela, Mitchell J., Huang, Wen-Yi, Wong, Wendy, Berndt, Sonja I., Sampson, Joshua, De Almeida, Jonas, Abubakar, Mustapha, Hislop, Jada, Chen, Kai-Ling, Dagnall, Casey, Diaz-Mayoral, Norma, Ferrell, Mary, Furr, Michael, Gonzalez, Alex, Hicks, Belynda, Hubbard, Aubrey K., Hutchinson, Amy, Jiang, Kevin, Jones, Kristine, Liu, Jia, Loftfield, Erikka, Loukissas, Jennifer, Mabie, Jerome, Merkle, Shannon, Miller, Eric, Minasian, Lori M., Nordgren, Ellen, Park, Brian, Pinsky, Paul, Riley, Thomas, Sandoval, Lorena, Saxena, Neeraj, Vogt, Aurelie, Wang, Jiahui, Williams, Craig, Wright, Patrick, Yeager, Meredith, Zhu, Bin, Zhu, Claire, Chanock, Stephen J., Garcia-Closas, Montserrat, and Freedman, Neal D.
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- 2023
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14. Invited Perspective: Polyaromatic Hydrocarbons in Alcohol--An Unappreciated Carcinogenic Mechanism?
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Berrigan, David and Freedman, Neal D.
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Meat ,Polycyclic aromatic hydrocarbons ,Environmental issues ,Health - Abstract
Polycyclic aromatic hydrocarbons (PAHs) are a large class of organic compounds produced by the incomplete combustion of fossil fuels as well as from high heat applied to organic matter such [...]
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- 2024
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15. A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate
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Rhee, Jongeun, Loftfield, Erikka, Albanes, Demetrius, Layne, Tracy M., Stolzenberg-Solomon, Rachael, Liao, Linda M., Playdon, Mary C., Berndt, Sonja I., Sampson, Joshua N., Freedman, Neal D., Moore, Steven C., and Purdue, Mark P.
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- 2023
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16. Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case–control study
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Yin, Jian, Freedman, Neal D., Liu, Yiwei, Dawsey, Sanford M., Yang, Huan, Taylor, Philip R., Yin, Liangyu, Liu, Bin, Cui, Jianfeng, Fan, Jinhu, Chen, Wen, Qiao, Youlin, and Abnet, Christian C.
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- 2023
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17. Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project
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Wu, Zeni, Petrick, Jessica L., Florio, Andrea A., Guillemette, Chantal, Beane Freeman, Laura E., Buring, Julie E., Bradwin, Gary, Caron, Patrick, Chen, Yu, Eliassen, A. Heather, Engel, Lawrence S., Freedman, Neal D., Gaziano, J. Michael, Giovannuci, Edward L., Hofmann, Jonathan N., Huang, Wen-Yi, Kirsh, Victoria A., Kitahara, Cari M., Koshiol, Jill, Lee, I-Min, Liao, Linda M., Newton, Christina C., Palmer, Julie R., Purdue, Mark P., Rohan, Thomas E., Rosenberg, Lynn, Sesso, Howard D., Sinha, Rashmi, Stampfer, Meir J., Um, Caroline Y., Van Den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Zeleniuch-Jacquotte, Anne, Zhang, Xuehong, Graubard, Barry I., Campbell, Peter T., and McGlynn, Katherine A.
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- 2023
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18. Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project
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Jackson, Sarah S, Adami, Hans-Olov, Andreotti, Gabriella, Beane-Freeman, Laura E, de González, Amy Berrington, Buring, Julie E, Fraser, Gary E, Freedman, Neal D, Gapstur, Susan M, Gierach, Gretchen, Giles, Graham G, Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kirsh, Victoria, Knutsen, Synnove F, Lan, Qing, Larsson, Susanna C, Lee, I-Min, Lee, Mei-Hsuan, Liao, Linda M, Milne, Roger L, Monroe, Kristine R, Neuhouser, Marian L, O'Brien, Katie M, Petrick, Jessica L, Purdue, Mark P, Rohan, Thomas E, Sandin, Sven, Sandler, Dale P, Sawada, Norie, Shadyab, Aladdin H, Simon, Tracey G, Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Weiderpass, Elisabete, Wolk, Alicja, Yang, Hwai-I, Zheng, Wei, McGlynn, Katherine A, Campbell, Peter T, and Koshiol, Jill
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Biomedical and Clinical Sciences ,Clinical Sciences ,Aging ,Prevention ,Clinical Research ,Contraception/Reproduction ,Digestive Diseases ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Reproductive health and childbirth ,Adult ,Aged ,Biliary Tract Neoplasms ,Female ,Follow-Up Studies ,Global Health ,Humans ,Incidence ,Middle Aged ,Prospective Studies ,Registries ,Reproduction ,Risk Assessment ,Risk Factors ,Sex Factors ,Survival Rate ,Time Factors ,Young Adult ,Reproductive factors ,Parity ,Biliary tract cancer ,Gallbladder cancer ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsGallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.MethodsWe pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.ResultsDuring 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.ConclusionWe observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.Lay summaryOur findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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- 2020
19. Abdominal and gluteofemoral size and risk of liver cancer: The liver cancer pooling project
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Florio, Andrea A, Campbell, Peter T, Zhang, Xuehong, Zeleniuch‐Jacquotte, Anne, Wactawski‐Wende, Jean, Smith‐Warner, Stephanie A, Sinha, Rashmi, Simon, Tracey G, Sesso, Howard D, Schairer, Catherine, Rosenberg, Lynn, Rohan, Thomas E, Robien, Kim, Renehan, Andrew G, Purdue, Mark P, Poynter, Jenny N, Palmer, Julie R, Newton, Christina C, Lu, Yunxia, Linet, Martha S, Liao, Linda M, Lee, I‐Min, Koshiol, Jill, Kitahara, Cari M, Kirsh, Victoria A, Hofmann, Jonathan N, Graubard, Barry I, Giovannucci, Edward, Gaziano, John M, Gapstur, Susan M, Freedman, Neal D, Demuth, Jane, Chong, Dawn Q, Chan, Andrew T, Buring, Julie E, Bradshaw, Patrick T, Freeman, Laura E Beane, McGlynn, Katherine A, and Petrick, Jessica L
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Obesity ,Rare Diseases ,Cancer ,Liver Disease ,Digestive Diseases ,Clinical Research ,Liver Cancer ,Prevention ,Adiposity ,Adult ,Aged ,Bile Duct Neoplasms ,Body Mass Index ,Carcinoma ,Hepatocellular ,Cholangiocarcinoma ,Female ,Humans ,Liver Neoplasms ,Male ,Middle Aged ,Prospective Studies ,Waist Circumference ,Waist-Hip Ratio ,hepatocellular carcinoma ,intrahepatic cholangiocarcinoma ,abdominal obesity ,gluteofemoral obesity ,epidemiology ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to
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- 2020
20. Exogenous hormone use, reproductive factors and risk of intrahepatic cholangiocarcinoma among women: results from cohort studies in the Liver Cancer Pooling Project and the UK Biobank
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Petrick, Jessica L, McMenamin, Úna C, Zhang, Xuehong, Zeleniuch-Jacquotte, Anne, Wactawski-Wende, Jean, Simon, Tracey G, Sinha, Rashmi, Sesso, Howard D, Schairer, Catherine, Rosenberg, Lynn, Rohan, Thomas E, Robien, Kim, Purdue, Mark P, Poynter, Jenny N, Palmer, Julie R, Lu, Yunxia, Linet, Martha S, Liao, Linda M, Lee, I-Min, Koshiol, Jill, Kitahara, Cari M, Kirsh, Victoria A, Hofmann, Jonathan N, Graubard, Barry I, Giovannucci, Edward, Gaziano, J Michael, Gapstur, Susan M, Freedman, Neal D, Florio, Andrea A, Chong, Dawn Q, Chen, Yu, Chan, Andrew T, Buring, Julie E, Freeman, Laura E Beane, Bea, Jennifer W, Cardwell, Christopher R, Campbell, Peter T, and McGlynn, Katherine A
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Liver Disease ,Cancer ,Digestive Diseases ,Contraception/Reproduction ,Clinical Research ,Digestive Diseases - (Gallbladder) ,Liver Cancer ,Prevention ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Reproductive health and childbirth ,Good Health and Well Being ,Aged ,Bile Ducts ,Bile Ducts ,Intrahepatic ,Biological Specimen Banks ,Cholangiocarcinoma ,Cohort Studies ,Contraceptives ,Oral ,Hormonal ,Estrogen Receptor alpha ,Estrogen Receptor beta ,Female ,Gene Expression Regulation ,Neoplastic ,Hormones ,Humans ,Hysterectomy ,Liver Neoplasms ,Menopause ,Middle Aged ,Proportional Hazards Models ,Risk Factors ,United Kingdom ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundIntrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC.MethodsWe harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases).ResultsHysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors.ConclusionsThis study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.
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- 2020
21. The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies
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Watts, Eleanor L, Perez‐Cornago, Aurora, Appleby, Paul N, Albanes, Demetrius, Ardanaz, Eva, Black, Amanda, Bueno‐de‐Mesquita, H Bas, Chan, June M, Chen, Chu, Chubb, SA Paul, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, English, Dallas R, Flicker, Leon, Freedman, Neal D, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Häggström, Christel, Haiman, Christopher, Hamdy, Freddie C, Hercberg, Serge, Holly, Jeff M, Huang, Jiaqi, Huang, Wen‐Yi, Johansson, Mattias, Kaaks, Rudolf, Kubo, Tatsuhiko, Lane, J Athene, Layne, Tracy M, Le Marchand, Loic, Martin, Richard M, Metter, E Jeffrey, Mikami, Kazuya, Milne, Roger L, Morris, Howard A, Mucci, Lorelei A, Neal, David E, Neuhouser, Marian L, Oliver, Steven E, Overvad, Kim, Ozasa, Kotaro, Pala, Valeria, Pernar, Claire H, Pollak, Michael, Rowlands, Mari‐Anne, Schaefer, Catherine A, Schenk, Jeannette M, Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Touvier, Mathilde, Trichopoulou, Antonia, Tsilidis, Konstantinos K, Van Den Eeden, Stephen K, Weinstein, Stephanie J, Wilkens, Lynne, Yeap, Bu B, Key, Timothy J, Allen, Naomi E, and Travis, Ruth C
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Cancer ,Aging ,Urologic Diseases ,Adult ,Aged ,Aged ,80 and over ,Anthropometry ,Biomarkers ,Tumor ,Cross-Sectional Studies ,Humans ,Insulin-Like Growth Factor Binding Proteins ,Insulin-Like Growth Factor I ,Insulin-Like Growth Factor II ,Male ,Middle Aged ,Neoplasms ,Prospective Studies ,Young Adult ,IGFs ,IGFBPs ,pooled analysis ,correlates ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
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- 2019
22. Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding
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Lee, Olivia W., Rodrigues, Calvin, Lin, Shu-Hong, Luo, Wen, Jones, Kristine, Brown, Derek W., Zhou, Weiyin, Karlins, Eric, Khan, Sairah M., Baulande, Sylvain, Raynal, Virginie, Surdez, Didier, Reynaud, Stephanie, Rubio, Rebeca Alba, Zaidi, Sakina, Grossetête, Sandrine, Ballet, Stelly, Lapouble, Eve, Laurence, Valérie, Pierron, Gaelle, Gaspar, Nathalie, Corradini, Nadège, Marec-Bérard, Perrine, Rothman, Nathaniel, Dagnall, Casey L., Burdett, Laurie, Manning, Michelle, Wyatt, Kathleen, Yeager, Meredith, Chari, Raj, Leisenring, Wendy M., Kulozik, Andreas E., Kriebel, Jennifer, Meitinger, Thomas, Strauch, Konstantin, Kirchner, Thomas, Dirksen, Uta, Mirabello, Lisa, Tucker, Margaret A., Tirode, Franck, Armstrong, Gregory T., Bhatia, Smita, Robison, Leslie L., Yasui, Yutaka, Romero-Pérez, Laura, Hartmann, Wolfgang, Metzler, Markus, Diver, W. Ryan, Lori, Adriana, Freedman, Neal D., Hoover, Robert N., Morton, Lindsay M., Chanock, Stephen J., Grünewald, Thomas G.P., Delattre, Olivier, and Machiela, Mitchell J.
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- 2023
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23. Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial
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O’Connor, Lauren E., Hall, Kevin D., Herrick, Kirsten A., Reedy, Jill, Chung, Stephanie T., Stagliano, Michael, Courville, Amber B., Sinha, Rashmi, Freedman, Neal D., Hong, Hyokyoung G., Albert, Paul S., and Loftfield, Erikka
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- 2023
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24. Urinary nitrate and sodium in a high-risk area for upper gastrointestinal cancers: Golestan Cohort Study☆
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Etemadi, Arash, Buller, Ian D., Hashemian, Maryam, Roshandel, Gholamreza, Poustchi, Hossein, Espinosa, Maria Morel, Blount, Benjamin C., Pfeiffer, Christine M., Keshavarzi, Behnam, Flory, Abigail R., Nasseri-Moghaddam, Siavosh, Dawsey, Sanford M., Freedman, Neal D., Abnet, Christian C., Malekzadeh, Reza, and Ward, Mary H.
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- 2022
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25. Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies
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Watts, Eleanor L, Appleby, Paul N, Perez-Cornago, Aurora, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cohn, Barbara A, Cook, Michael B, Flicker, Leon, Freedman, Neal D, Giles, Graham G, Giovannucci, Edward, Gislefoss, Randi E, Hankey, Graeme J, Kaaks, Rudolf, Knekt, Paul, Kolonel, Laurence N, Kubo, Tatsuhiko, Le Marchand, Loïc, Luben, Robert N, Luostarinen, Tapio, Männistö, Satu, Metter, E Jeffrey, Mikami, Kazuya, Milne, Roger L, Ozasa, Kotaro, Platz, Elizabeth A, Quirós, J Ramón, Rissanen, Harri, Sawada, Norie, Stampfer, Meir, Stanczyk, Frank Z, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Thompson, Ian M, Tsilidis, Konstantinos K, Tsugane, Shoichiro, Ursin, Giske, Vatten, Lars, Weiss, Noel S, Yeap, Bu B, Allen, Naomi E, Key, Timothy J, and Travis, Ruth C
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Cancer ,Clinical Research ,Prevention ,Urologic Diseases ,Prostate Cancer ,Aging ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Aged ,Biomarkers ,Case-Control Studies ,Down-Regulation ,Humans ,Male ,Middle Aged ,Neoplasm Grading ,Prospective Studies ,Prostatic Neoplasms ,Protective Factors ,Risk Assessment ,Risk Factors ,Testosterone ,Time Factors ,Androgens Pooled analysis ,Prospective studies ,Prostate cancer ,Sex hormones ,Epidemiology ,Androgens ,Pooled analysis ,Clinical Sciences ,Urology & Nephrology - Abstract
BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p
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- 2018
26. Integrated Analysis of Coexpression and Exome Sequencing to Prioritize Susceptibility Genes for Familial Cutaneous Melanoma
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Yepes, Sally, Tucker, Margaret A., Koka, Hela, Xiao, Yanzi, Zhang, Tongwu, Jones, Kristine, Vogt, Aurelie, Burdette, Laurie, Luo, Wen, Zhu, Bin, Hutchinson, Amy, Yeager, Meredith, Hicks, Belynda, Brown, Kevin M., Freedman, Neal D., Chanock, Stephen J., Goldstein, Alisa M., and Yang, Xiaohong R.
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- 2022
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27. Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes
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McReynolds, Lisa J., Rafati, Maryam, Wang, Youjin, Ballew, Bari J., Kim, Jung, Williams, Valencia V., Zhou, Weiyin, Hendricks, Rachel M., Dagnall, Casey, Freedman, Neal D., Carter, Brian, Strollo, Sara, Hicks, Belynda, Zhu, Bin, Jones, Kristine, Paczesny, Sophie, Marsh, Steven G.E., Spellman, Stephen R., He, Meilun, Wang, Tao, Lee, Stephanie J., Savage, Sharon A., and Gadalla, Shahinaz M.
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- 2022
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28. Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis
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Brown, Derek W., Zhou, Weiyin, Wang, Youjin, Jones, Kristine, Luo, Wen, Dagnall, Casey, Teshome, Kedest, Klein, Alyssa, Zhang, Tongwu, Lin, Shu-Hong, Lee, Olivia W., Khan, Sairah, Vo, Jacqueline B., Hutchinson, Amy, Liu, Jia, Wang, Jiahui, Zhu, Bin, Hicks, Belynda, Martin, Andrew St., Spellman, Stephen R., Wang, Tao, Deeg, H. Joachim, Gupta, Vikas, Lee, Stephanie J., Freedman, Neal D., Yeager, Meredith, Chanock, Stephen J., Savage, Sharon A., Saber, Wael, Gadalla, Shahinaz M., and Machiela, Mitchell J.
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- 2022
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29. COVID-19 SeroHub, an online repository of SARS-CoV-2 seroprevalence studies in the United States
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Freedman, Neal D., Brown, Liliana, Newman, Lori M., Jones, Jefferson M., Benoit, Tina J., Averhoff, Francisco, Bu, Xiangning, Bayrak, Konuralp, Lu, Anna, Coffey, Brent, Jackson, Latifa, Chanock, Stephen J., and Kerlavage, Anthony R.
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- 2022
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30. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
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Jiang, Xia, O’Reilly, Paul F, Aschard, Hugues, Hsu, Yi-Hsiang, Richards, J Brent, Dupuis, Josée, Ingelsson, Erik, Karasik, David, Pilz, Stefan, Berry, Diane, Kestenbaum, Bryan, Zheng, Jusheng, Luan, Jianan, Sofianopoulou, Eleni, Streeten, Elizabeth A, Albanes, Demetrius, Lutsey, Pamela L, Yao, Lu, Tang, Weihong, Econs, Michael J, Wallaschofski, Henri, Völzke, Henry, Zhou, Ang, Power, Chris, McCarthy, Mark I, Michos, Erin D, Boerwinkle, Eric, Weinstein, Stephanie J, Freedman, Neal D, Huang, Wen-Yi, Van Schoor, Natasja M, van der Velde, Nathalie, Groot, Lisette CPGM de, Enneman, Anke, Cupples, L Adrienne, Booth, Sarah L, Vasan, Ramachandran S, Liu, Ching-Ti, Zhou, Yanhua, Ripatti, Samuli, Ohlsson, Claes, Vandenput, Liesbeth, Lorentzon, Mattias, Eriksson, Johan G, Shea, M Kyla, Houston, Denise K, Kritchevsky, Stephen B, Liu, Yongmei, Lohman, Kurt K, Ferrucci, Luigi, Peacock, Munro, Gieger, Christian, Beekman, Marian, Slagboom, Eline, Deelen, Joris, Heemst, Diana van, Kleber, Marcus E, März, Winfried, de Boer, Ian H, Wood, Alexis C, Rotter, Jerome I, Rich, Stephen S, Robinson-Cohen, Cassianne, den Heijer, Martin, Jarvelin, Marjo-Riitta, Cavadino, Alana, Joshi, Peter K, Wilson, James F, Hayward, Caroline, Lind, Lars, Michaëlsson, Karl, Trompet, Stella, Zillikens, M Carola, Uitterlinden, Andre G, Rivadeneira, Fernando, Broer, Linda, Zgaga, Lina, Campbell, Harry, Theodoratou, Evropi, Farrington, Susan M, Timofeeva, Maria, Dunlop, Malcolm G, Valdes, Ana M, Tikkanen, Emmi, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Raitakari, Olli T, Mikkilä, Vera, Ikram, M Arfan, Sattar, Naveed, Jukema, J Wouter, Wareham, Nicholas J, Langenberg, Claudia, Forouhi, Nita G, Gundersen, Thomas E, Khaw, Kay-Tee, Butterworth, Adam S, Danesh, John, and Spector, Timothy
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Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Amidohydrolases ,Autoimmune Diseases ,Cohort Studies ,Female ,Genome-Wide Association Study ,Humans ,Male ,Polymorphism ,Single Nucleotide ,Vesicular Transport Proteins ,Vitamin D ,White People - Abstract
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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- 2018
31. Severe housing cost burden and premature mortality from cancer
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Lawrence, Wayne R, primary, Freedman, Neal D, additional, McGee-Avila, Jennifer K, additional, Mason, Lee, additional, Chen, Yingxi, additional, Ewing, Aldenise P, additional, and Shiels, Meredith S, additional
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- 2024
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32. An investigation of cross-sectional associations of a priori–selected dietary components with circulating bile acids
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Byrd, Doratha A, Sinha, Rashmi, Weinstein, Stephanie J, Albanes, Demetrius, Freedman, Neal D, Sampson, Joshua, and Loftfield, Erikka
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- 2021
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33. Tobacco Smoking and Risk of Second Primary Lung Cancer
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Aredo, Jacqueline V., Luo, Sophia J., Gardner, Rebecca M., Sanyal, Nilotpal, Choi, Eunji, Hickey, Thomas P., Riley, Thomas L., Huang, Wen-Yi, Kurian, Allison W., Leung, Ann N., Wilkens, Lynne R., Robbins, Hilary A., Riboli, Elio, Kaaks, Rudolf, Tjønneland, Anne, Vermeulen, Roel C.H., Panico, Salvatore, Le Marchand, Loïc, Amos, Christopher I., Hung, Rayjean J., Freedman, Neal D., Johansson, Mattias, Cheng, Iona, Wakelee, Heather A., and Han, Summer S.
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- 2021
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34. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study
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Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O’Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t’Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, Woo, Daniel, and Rosand, Jonathan
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Clinical Research ,Cancer ,Prevention ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Aged ,Aged ,80 and over ,Cardiovascular Diseases ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Germ-Line Mutation ,Humans ,Male ,Mendelian Randomization Analysis ,Middle Aged ,Neoplasms ,Polymorphism ,Single Nucleotide ,Risk Assessment ,Telomere ,Telomere Homeostasis ,Telomeres Mendelian Randomization Collaboration ,Public Health and Health Services ,Oncology and carcinogenesis - Abstract
ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- 2017
35. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.
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Telomeres Mendelian Randomization Collaboration, Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O'Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t'Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, and Woo, Daniel
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Telomeres Mendelian Randomization Collaboration ,Telomere ,Humans ,Neoplasms ,Cardiovascular Diseases ,Genetic Predisposition to Disease ,Risk Assessment ,Germ-Line Mutation ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Mendelian Randomization Analysis ,Telomere Homeostasis ,Polymorphism ,Single Nucleotide ,and over ,Prevention ,Clinical Research ,Cancer ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Public Health and Health Services - Abstract
ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- 2017
36. Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California
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IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Jones, Rena R, Fisher, Jared A, Hasheminassab, Sina, Kaufman, Joel D, Freedman, Neal D, Ward, Mary H, Sioutas, Constantinos, Vermeulen, Roel, Hoek, Gerard, Silverman, Debra T, IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Jones, Rena R, Fisher, Jared A, Hasheminassab, Sina, Kaufman, Joel D, Freedman, Neal D, Ward, Mary H, Sioutas, Constantinos, Vermeulen, Roel, Hoek, Gerard, and Silverman, Debra T
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- 2024
37. Prevalence and Incidence of Metabolic Syndrome and Its Components Among Waterpipe Users.
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Sadeghi, Yasaman, Naghash, Mahdokht, Poustchi, Hossein, Alvand, Saba, Gandomkar, Abdullah, Vardanjani, Hossein Molavi, Malekzadeh, Fatemeh, Boffetta, Paolo, Abnet, Christian C., Freedman, Neal D., Malekzadeh, Reza, and Etemadi, Arash
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METABOLIC syndrome ,FASTING ,HDL cholesterol ,SMOKING cessation ,BLOOD sugar ,WAIST circumference - Abstract
Objectives: To determine the associations between waterpipe use, duration, and intensity of use with prevalence and incidence of metabolic syndrome and its components (increased waist circumference, triglycerides, fasting glucose, blood pressure and decreased high-density lipoprotein cholesterol). Methods: We conducted cross-sectional and prospective analyses using data from the Pars Cohort Study in southern Iran, encompassing 9,264 participants at the baseline, and 5,002 randomly selected in a repeated follow-up. We used multivariate logistic regression models adjusted for age, sex, education, wealth score, physical activity and cigarette pack-years to report odds ratios (OR) and 95% confidence intervals (CI). Results: Among 9,264 participants, 3,119 (33.7%) had metabolic syndrome, and 3,482 (37.6%) had ever smoked waterpipe, with both more common in women than in men. In adjusted models, former waterpipe use was significantly associated with prevalence (OR = 1.43, 95% CI: 1.23–1.68) and incidence (OR = 1.57, 95% CI: 1.19–2.06) of the metabolic syndrome while current waterpipe use was not. Past use was associated with increased risk in all components of metabolic syndrome; current use was associated with increases in all except high blood glucose and hypertension. Past waterpipe users had higher waterpipe use intensity (before quitting) in comparison with current users (2.3 vs. 2.0 waterpipes per day, p < 0.01) and had started waterpipe smoking at a younger age (27.2 vs. 30.1 years, p < 0.01). Conclusion: Waterpipe use was associated with metabolic syndrome and its components, especially among former users potentially due to higher intensity and earlier initiation of use. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study
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Sheikh, Mahdi, Shakeri, Ramin, Poustchi, Hossein, Pourshams, Akram, Etemadi, Arash, Islami, Farhad, Khoshnia, Masoud, Gharavi, Abdolsamad, Roshandel, Gholamreza, Khademi, Hooman, Sepanlou, Sadaf G, Hashemian, Maryam, Fazel, Abdolreza, Zahedi, Mahdi, Abedi-Ardekani, Behnoush, Boffetta, Paolo, Dawsey, Sanford M, Pharoah, Paul D, Sotoudeh, Masoud, Freedman, Neal D, Abnet, Christian C, Day, Nicholas E, Brennan, Paul, Kamangar, Farin, and Malekzadeh, Reza
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- 2020
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39. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
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Machiela, Mitchell J, Zhou, Weiyin, Karlins, Eric, Sampson, Joshua N, Freedman, Neal D, Yang, Qi, Hicks, Belynda, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C, Amos, Christopher, Amundadottir, Laufey T, Arslan, Alan A, Beane-Freeman, Laura E, Berndt, Sonja I, Black, Amanda, Blot, William J, Bock, Cathryn H, Bracci, Paige M, Brinton, Louise A, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie E, Butler, Mary A, Canzian, Federico, Carreon, Tania, Chaffee, Kari G, Chang, I-Shou, Chatterjee, Nilanjan, Chen, Chu, Chen, Constance, Chen, Kexin, Chung, Charles C, Cook, Linda S, Bou, Marta Crous, Cullen, Michael, Davis, Faith G, De Vivo, Immaculata, Ding, Ti, Doherty, Jennifer, Duell, Eric J, Epstein, Caroline G, Fan, Jin-Hu, Figueroa, Jonine D, Fraumeni, Joseph F, Friedenreich, Christine M, Fuchs, Charles S, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, Garcia-Closas, Montserrat, Gaudet, Mia M, Gaziano, J Michael, Giles, Graham G, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Goran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, Wei, Hunter, David J, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Alison P, Klein, Robert, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C, LaCroix, Andrea, Lan, Qing, Landi, Maria Teresa, Le Marchand, Loic, Li, Donghui, Liang, Xiaolin, Liao, Linda M, Lin, Dongxin, Liu, Jianjun, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, and Malats, Nuria
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- 2016
40. Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials.
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Loftfield, Erikka, O'Brien, Thomas R, Pfeiffer, Ruth M, Howell, Charles D, Horst, Ron, Prokunina-Olsson, Ludmila, Weinstein, Stephanie J, Albanes, Demetrius, Morgan, Timothy R, and Freedman, Neal D
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Humans ,Hepacivirus ,Hepatitis C ,Chronic ,Vitamins ,Vitamin D ,Interferon-alpha ,Ribavirin ,Antiviral Agents ,Treatment Outcome ,Adult ,Middle Aged ,Female ,Male ,Hepatitis C ,Chronic ,General Science & Technology - Abstract
ConclusionHigher vitamin D status was not beneficially associated with responses to therapy; if anything, patients with higher vitamin D concentrations were less likely to attain SVR. Our data do not support a role for vitamin D supplementation as an adjuvant therapy for HCV.
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- 2016
41. Incidence of Lung Adenocarcinoma by Age, Sex, and Smoking Status in Taiwan
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Chien, Li-Hsin, primary, Jiang, Hsin-Fang, additional, Tsai, Fang-Yu, additional, Chang, Hsing-Yi, additional, Freedman, Neal D., additional, Rothman, Nathaniel, additional, Lan, Qing, additional, Hsiung, Chao A., additional, and Chang, I-Shou, additional
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- 2023
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42. ABO genotypes and the risk of esophageal and gastric cancers
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Chen, Yingxi, Hu, Nan, Liao, Linda, Yu, Kai, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Qiao, You-Lin, Fan, Jin-Hu, Dawsey, Sanford M., Freedman, Neal D., Taylor, Philip R., Goldstein, Alisa M., and Abnet, Christian C.
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- 2021
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43. Associations of Helicobacter pylori and hepatitis A seropositivity with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): addressing the hygiene hypothesis
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Alvarez, Christian S., Avilés-Santa, M. Larissa, Freedman, Neal D., Perreira, Krista M., Garcia-Bedoya, Olga, Kaplan, Robert C., Daviglus, Martha L., Graubard, Barry I., Talavera, Gregory A., Thyagarajan, Bharat, and Camargo, M. Constanza
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- 2021
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44. Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults
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Zahed, Hana, Johansson, Mattias, Ueland, Per M., Midttun, Øivind, Milne, Roger L., Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Grankvist, Kjell, Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loic, Wilkens, Lynne R., Weinstein, Stephanie J., Albanes, Demetrius, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Muller, David, Brennan, Paul, Guida, Florence, and Robbins, Hilary A.
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- 2021
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45. Characterization of Large Structural Genetic Mosaicism in Human Autosomes
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Machiela, Mitchell J, Zhou, Weiyin, Sampson, Joshua N, Dean, Michael C, Jacobs, Kevin B, Black, Amanda, Brinton, Louise A, Chang, I-Shou, Chen, Chu, Chen, Constance, Chen, Kexin, Cook, Linda S, Bou, Marta Crous, De Vivo, Immaculata, Doherty, Jennifer, Friedenreich, Christine M, Gaudet, Mia M, Haiman, Christopher A, Hankinson, Susan E, Hartge, Patricia, Henderson, Brian E, Hong, Yun-Chul, Hosgood, H Dean, Hsiung, Chao A, Hu, Wei, Hunter, David J, Jessop, Lea, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Robert, Kraft, Peter, Lan, Qing, Lin, Dongxin, Liu, Jianjun, Le Marchand, Loic, Liang, Xiaolin, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, Matsuo, Keitaro, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Pooler, Loreall, Prescott, Jennifer, Rastogi, Radhai, Risch, Harvey A, Schumacher, Fredrick, Seow, Adeline, Setiawan, Veronica Wendy, Shen, Hongbing, Sheng, Xin, Shin, Min-Ho, Shu, Xiao-Ou, Berg, David VanDen, Wang, Jiu-Cun, Wentzensen, Nicolas, Wong, Maria Pik, Wu, Chen, Wu, Tangchun, Wu, Yi-Long, Xia, Lucy, Yang, Hannah P, Yang, Pan-Chyr, Zheng, Wei, Zhou, Baosen, Abnet, Christian C, Albanes, Demetrius, Aldrich, Melinda C, Amos, Christopher, Amundadottir, Laufey T, Berndt, Sonja I, Blot, William J, Bock, Cathryn H, Bracci, Paige M, Burdett, Laurie, Buring, Julie E, Butler, Mary A, Carreón, Tania, Chatterjee, Nilanjan, Chung, Charles C, Cook, Michael B, Cullen, Michael, Davis, Faith G, Ding, Ti, Duell, Eric J, Epstein, Caroline G, Fan, Jin-Hu, Figueroa, Jonine D, Fraumeni, Joseph F, Freedman, Neal D, Fuchs, Charles S, Gao, Yu-Tang, Gapstur, Susan M, Patiño-Garcia, Ana, Garcia-Closas, Montserrat, Gaziano, J Michael, Giles, Graham G, and Gillanders, Elizabeth M
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Biological Sciences ,Genetics ,Human Genome ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Aged ,Chromosome Aberrations ,Female ,Genome ,Human ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Middle Aged ,Mosaicism ,Neoplasms ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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- 2015
46. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
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Wang, Zhaoming, Zhu, Bin, Zhang, Mingfeng, Parikh, Hemang, Jia, Jinping, Chung, Charles C, Sampson, Joshua N, Hoskins, Jason W, Hutchinson, Amy, Burdette, Laurie, Ibrahim, Abdisamad, Hautman, Christopher, Raj, Preethi S, Abnet, Christian C, Adjei, Andrew A, Ahlbom, Anders, Albanes, Demetrius, Allen, Naomi E, Ambrosone, Christine B, Aldrich, Melinda, Amiano, Pilar, Amos, Christopher, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Arici, Cecilia, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Beane Freeman, Laura E, Berg, Christine D, Berndt, Sonja I, Bertazzi, Pier Alberto, Biritwum, Richard B, Black, Amanda, Blot, William, Boeing, Heiner, Boffetta, Paolo, Bolton, Kelly, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brennan, Paul, Brinton, Louise A, Brotzman, Michelle, Bueno-de-Mesquita, H Bas, Buring, Julie E, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Cao, Guangwen, Caporaso, Neil E, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chang, Gee-Chen, Chang, I-Shou, Chang-Claude, Jenny, Che, Xu, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chung-Hsing, Chen, Constance, Chen, Kuan-Yu, Chen, Yuh-Min, Chokkalingam, Anand P, Chu, Lisa W, Clavel-Chapelon, Francoise, Colditz, Graham A, Colt, Joanne S, Conti, David, Cook, Michael B, Cortessis, Victoria K, Crawford, E David, Cussenot, Olivier, Davis, Faith G, De Vivo, Immaculata, Deng, Xiang, Ding, Ti, Dinney, Colin P, Di Stefano, Anna Luisa, Diver, W Ryan, Duell, Eric J, Elena, Joanne W, Fan, Jin-Hu, Feigelson, Heather Spencer, Feychting, Maria, Figueroa, Jonine D, Flanagan, Adrienne M, Fraumeni, Joseph F, Freedman, Neal D, Fridley, Brooke L, Fuchs, Charles S, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, and Garcia-Closas, Montserrat
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Biological Sciences ,Genetics ,Cancer ,Clinical Research ,Human Genome ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,Alleles ,Chromosomes ,Human ,Pair 5 ,Computational Biology ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Gene Expression Regulation ,Neoplastic ,Gene Frequency ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Male ,Membrane Proteins ,Neoplasm Proteins ,Neoplasms ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Risk ,Telomerase ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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- 2014
47. Premature mortality from all causes and drug poisonings in the USA according to socioeconomic status and rurality: an analysis of death certificate data by county from 2000–15
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Shiels, Meredith S, Berrington de González, Amy, Best, Ana F, Chen, Yingxi, Chernyavskiy, Pavel, Hartge, Patricia, Khan, Sahar Q, Pérez-Stable, Eliseo J, Rodriquez, Erik J, Spillane, Susan, Thomas, David A, Withrow, Diana, and Freedman, Neal D
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- 2019
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48. Association between aflatoxin-albumin adduct levels and tortilla consumption in Guatemalan adults
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Kroker-Lobos, María F., Alvarez, Christian S., Rivera-Andrade, Alvaro, Smith, Joshua W., Egner, Patricia, Torres, Olga, Lazo, Mariana, Freedman, Neal D., Guallar, Eliseo, Graubard, Barry I., McGlynn, Katherine A., Ramírez-Zea, Manuel, and Groopman, John D.
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- 2019
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49. Opioid use in cancer patients compared with noncancer pain patients in a veteran population.
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Mudumbai, Seshadri C, He, Han, Chen, Ji-Qing, Kapoor, Aditi, Regala, Samantha, Mariano, Edward R, Stafford, Randall S, Abnet, Christian C, Pfeiffer, Ruth M, Freedman, Neal D, and Etemadi, Arash
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OPIOIDS ,CANCER patient care ,CANCER pain - Abstract
Background Opioid safety initiatives may secondarily impact opioid prescribing and pain outcomes for cancer care. Methods We reviewed electronic health record data at a tertiary Veterans Affairs system (VA Palo Alto) for all patients from 2015 to 2021. We collected outpatient Schedule II opioid prescriptions data and calculated morphine milligram equivalents (MMEs) using Centers for Disease Control and Prevention conversion formulas. To determine the clinical impact of changes in opioid prescription, we used the highest level of pain reported by each patient on the 0-to-10 Numeric Rating Scale in each year, categorized into mild (0-3), moderate (4-6), and severe (7 and above). Results Among 89 569 patients, 9073 had a cancer diagnosis. Cancer patients were almost twice as likely to have an opioid prescription compared with noncancer patients (69.0% vs 36.7%, respectively). The proportion of patients who received an opioid prescription decreased from 27.1% to 18.1% (trend P < .01) in cancer patients and from 17.0% to 10.2% in noncancer patients (trend P < .01). Cancer and noncancer patients had similar declines of MMEs per year between 2015 and 2019, but the decline was more rapid for cancer patients (1462.5 to 946.4, 35.3%) compared with noncancer patients (1315.6 to 927.7, 29.5%) from 2019 to 2021. During the study period, the proportion of noncancer patients who experienced severe pain was almost unchanged, whereas it increased among cancer patients, reaching a significantly higher rate than among noncancer patients in 2021 (31.9% vs 27.4%, P < .01). Conclusions Our findings suggest potential unintended consequences for cancer care because of efforts to manage opioid-related risks. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort
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White, Alexandra J, primary, Fisher, Jared A, additional, Sweeney, Marina R, additional, Freedman, Neal D, additional, Kaufman, Joel D, additional, Silverman, Debra T, additional, and Jones, Rena R, additional
- Published
- 2023
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