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4. 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

Author

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

Subjects
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.

Published
2019

5. Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies

Author

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

Subjects
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

Published
2018

8. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men

Author

Watts, Eleanor L, Appleby, Paul N, Albanes, Demetrius, Black, Amanda, Chan, June M, Chen, Chu, Cirillo, Piera M, Cohn, Barbara A, Cook, Michael B, Donovan, Jenny L, Ferrucci, Luigi, Garland, Cedric F, Giles, Graham G, Goodman, Phyllis J, Habel, Laurel A, Haiman, Christopher A, Holly, Jeff MP, Hoover, Robert N, Kaaks, Rudolf, Knekt, Paul, Kolonel, Laurence N, Kubo, Tatsuhiko, Le Marchand, Loïc, Luostarinen, Tapio, MacInnis, Robert J, Mäenpää, Hanna O, Männistö, Satu, Metter, E Jeffrey, Milne, Roger L, Nomura, Abraham MY, Oliver, Steven E, Parsons, J Kellogg, Peeters, Petra H, Platz, Elizabeth A, Riboli, Elio, Ricceri, Fulvio, Rinaldi, Sabina, Rissanen, Harri, Sawada, Norie, Schaefer, Catherine A, Schenk, Jeannette M, Stanczyk, Frank Z, Stampfer, Meir, Stattin, Pär, Stenman, Ulf-Håkan, Tjønneland, Anne, Trichopoulou, Antonia, Thompson, Ian M, Tsugane, Shoichiro, Vatten, Lars, Whittemore, Alice S, Ziegler, Regina G, Allen, Naomi E, Key, Timothy J, and Travis, Ruth C

Subjects
Cancer, Aging, Estrogen, Good Health and Well Being, Adult, Anthropometry, Behavior, Datasets as Topic, Gonadal Steroid Hormones, Humans, Male, Social Class, Young Adult, General Science & Technology
Abstract

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Published
2017

9. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C, Appleby, Paul N, Martin, Richard M, Holly, Jeff MP, Albanes, Demetrius, Black, Amanda, Bueno-de-Mesquita, HB As, Chan, June M, Chen, Chu, Chirlaque, Maria-Dolores, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, Ferrucci, Luigi, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Hamdy, Freddie C, Helzlsouer, Kathy J, Hercberg, Serge, Hoover, Robert N, Janssen, Joseph AMJL, Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Metter, E Jeffrey, Mikami, Kazuya, Morris, Joan K, Neal, David E, Neuhouser, Marian L, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth A, Pollak, Michael, Price, Alison J, Roobol, Monique J, Schaefer, Catherine, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Touvier, Mathilde, Wald, Nicholas J, Weiss, Noel S, Ziegler, Regina G, Key, Timothy J, and Allen, Naomi E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Aged, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Prostatic Neoplasms, Risk Factors, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

Published
2016

13. Immune microenvironment profiling of normal appearing colorectal mucosa biopsied over repeat patient visits reproducibly separates lynch syndrome patients based on their history of colon cancer

Author

Brand, Rhonda M., primary, Dudley, Beth, additional, Karloski, Eve, additional, Zyhowski, Ashley, additional, Raphael, Rebecca, additional, Pitlor, Danielle, additional, Metter, E. Jeffrey, additional, Pai, Reet, additional, Lee, Kenneth, additional, Brand, Randall E., additional, and Uttam, Shikhar, additional

Published
2023
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15. Supplementary Materials and Methods from A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C., primary, Appleby, Paul N., primary, Martin, Richard M., primary, Holly, Jeff M.P., primary, Albanes, Demetrius, primary, Black, Amanda, primary, Bueno-de-Mesquita, H. Bas, primary, Chan, June M., primary, Chen, Chu, primary, Chirlaque, Maria-Dolores, primary, Cook, Michael B., primary, Deschasaux, Mélanie, primary, Donovan, Jenny L., primary, Ferrucci, Luigi, primary, Galan, Pilar, primary, Giles, Graham G., primary, Giovannucci, Edward L., primary, Gunter, Marc J., primary, Habel, Laurel A., primary, Hamdy, Freddie C., primary, Helzlsouer, Kathy J., primary, Hercberg, Serge, primary, Hoover, Robert N., primary, Janssen, Joseph A.M.J.L., primary, Kaaks, Rudolf, primary, Kubo, Tatsuhiko, primary, Le Marchand, Loic, primary, Metter, E. Jeffrey, primary, Mikami, Kazuya, primary, Morris, Joan K., primary, Neal, David E., primary, Neuhouser, Marian L., primary, Ozasa, Kotaro, primary, Palli, Domenico, primary, Platz, Elizabeth A., primary, Pollak, Michael N., primary, Price, Alison J., primary, Roobol, Monique J., primary, Schaefer, Catherine, primary, Schenk, Jeannette M., primary, Severi, Gianluca, primary, Stampfer, Meir J., primary, Stattin, Pär, primary, Tamakoshi, Akiko, primary, Tangen, Catherine M., primary, Touvier, Mathilde, primary, Wald, Nicholas J., primary, Weiss, Noel S., primary, Ziegler, Regina G., primary, Key, Timothy J., primary, and Allen, Naomi E., primary

Published
2023
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16. Supplementary Figure Legends from A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C., primary, Appleby, Paul N., primary, Martin, Richard M., primary, Holly, Jeff M.P., primary, Albanes, Demetrius, primary, Black, Amanda, primary, Bueno-de-Mesquita, H. Bas, primary, Chan, June M., primary, Chen, Chu, primary, Chirlaque, Maria-Dolores, primary, Cook, Michael B., primary, Deschasaux, Mélanie, primary, Donovan, Jenny L., primary, Ferrucci, Luigi, primary, Galan, Pilar, primary, Giles, Graham G., primary, Giovannucci, Edward L., primary, Gunter, Marc J., primary, Habel, Laurel A., primary, Hamdy, Freddie C., primary, Helzlsouer, Kathy J., primary, Hercberg, Serge, primary, Hoover, Robert N., primary, Janssen, Joseph A.M.J.L., primary, Kaaks, Rudolf, primary, Kubo, Tatsuhiko, primary, Le Marchand, Loic, primary, Metter, E. Jeffrey, primary, Mikami, Kazuya, primary, Morris, Joan K., primary, Neal, David E., primary, Neuhouser, Marian L., primary, Ozasa, Kotaro, primary, Palli, Domenico, primary, Platz, Elizabeth A., primary, Pollak, Michael N., primary, Price, Alison J., primary, Roobol, Monique J., primary, Schaefer, Catherine, primary, Schenk, Jeannette M., primary, Severi, Gianluca, primary, Stampfer, Meir J., primary, Stattin, Pär, primary, Tamakoshi, Akiko, primary, Tangen, Catherine M., primary, Touvier, Mathilde, primary, Wald, Nicholas J., primary, Weiss, Noel S., primary, Ziegler, Regina G., primary, Key, Timothy J., primary, and Allen, Naomi E., primary

Published
2023
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17. Supplementary Tables 1 through 8 and Supplementary Figures 1 through 15 from A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C., primary, Appleby, Paul N., primary, Martin, Richard M., primary, Holly, Jeff M.P., primary, Albanes, Demetrius, primary, Black, Amanda, primary, Bueno-de-Mesquita, H. Bas, primary, Chan, June M., primary, Chen, Chu, primary, Chirlaque, Maria-Dolores, primary, Cook, Michael B., primary, Deschasaux, Mélanie, primary, Donovan, Jenny L., primary, Ferrucci, Luigi, primary, Galan, Pilar, primary, Giles, Graham G., primary, Giovannucci, Edward L., primary, Gunter, Marc J., primary, Habel, Laurel A., primary, Hamdy, Freddie C., primary, Helzlsouer, Kathy J., primary, Hercberg, Serge, primary, Hoover, Robert N., primary, Janssen, Joseph A.M.J.L., primary, Kaaks, Rudolf, primary, Kubo, Tatsuhiko, primary, Le Marchand, Loic, primary, Metter, E. Jeffrey, primary, Mikami, Kazuya, primary, Morris, Joan K., primary, Neal, David E., primary, Neuhouser, Marian L., primary, Ozasa, Kotaro, primary, Palli, Domenico, primary, Platz, Elizabeth A., primary, Pollak, Michael N., primary, Price, Alison J., primary, Roobol, Monique J., primary, Schaefer, Catherine, primary, Schenk, Jeannette M., primary, Severi, Gianluca, primary, Stampfer, Meir J., primary, Stattin, Pär, primary, Tamakoshi, Akiko, primary, Tangen, Catherine M., primary, Touvier, Mathilde, primary, Wald, Nicholas J., primary, Weiss, Noel S., primary, Ziegler, Regina G., primary, Key, Timothy J., primary, and Allen, Naomi E., primary

Published
2023
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18. Data from A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk

Author

Travis, Ruth C., primary, Appleby, Paul N., primary, Martin, Richard M., primary, Holly, Jeff M.P., primary, Albanes, Demetrius, primary, Black, Amanda, primary, Bueno-de-Mesquita, H. Bas, primary, Chan, June M., primary, Chen, Chu, primary, Chirlaque, Maria-Dolores, primary, Cook, Michael B., primary, Deschasaux, Mélanie, primary, Donovan, Jenny L., primary, Ferrucci, Luigi, primary, Galan, Pilar, primary, Giles, Graham G., primary, Giovannucci, Edward L., primary, Gunter, Marc J., primary, Habel, Laurel A., primary, Hamdy, Freddie C., primary, Helzlsouer, Kathy J., primary, Hercberg, Serge, primary, Hoover, Robert N., primary, Janssen, Joseph A.M.J.L., primary, Kaaks, Rudolf, primary, Kubo, Tatsuhiko, primary, Le Marchand, Loic, primary, Metter, E. Jeffrey, primary, Mikami, Kazuya, primary, Morris, Joan K., primary, Neal, David E., primary, Neuhouser, Marian L., primary, Ozasa, Kotaro, primary, Palli, Domenico, primary, Platz, Elizabeth A., primary, Pollak, Michael N., primary, Price, Alison J., primary, Roobol, Monique J., primary, Schaefer, Catherine, primary, Schenk, Jeannette M., primary, Severi, Gianluca, primary, Stampfer, Meir J., primary, Stattin, Pär, primary, Tamakoshi, Akiko, primary, Tangen, Catherine M., primary, Touvier, Mathilde, primary, Wald, Nicholas J., primary, Weiss, Noel S., primary, Ziegler, Regina G., primary, Key, Timothy J., primary, and Allen, Naomi E., primary

Published
2023
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23. Risk of Alzheimer's disease and duration of NSAID use

Author

Stewart, Walter F, Kawas, Claudia, Corrada, Maria, and Metter, E Jeffrey

Subjects
Neurosciences, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Alzheimer's Disease, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Aging, Acetaminophen, Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Confidence Intervals, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk Assessment, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29) for those with less than 2 years of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.

Published
1997

26. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer:a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author

Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, and consortium, The PRACTICAL

Subjects
Cancer och onkologi, prospective analysis, Epidemiology, General Medicine, prostate cancer, aggressive prostate cancer, Cancer and Oncology, Mendelian randomization, international consortia, Insulin-like growth factor-I, ICEP, Bristol Population Health Science Institute
Abstract

Background Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Published
2022

36. High-resolution CT with arch/neck/head CT angiography on a mobile stroke unit

Author

Alexandrov, Anne W, primary, Arthur, Adam S, additional, Bryndziar, Tomas, additional, Swatzell, Victoria M, additional, Dusenbury, Wendy, additional, Hardage, Keri, additional, McCormick, Sarah, additional, Rhudy, James P, additional, Maleki, Ana Hossein Zadeh, additional, Singh, Savdeep, additional, Krishnaiah, Balaji, additional, Nearing, Katherine, additional, Rubin, Mark N, additional, Malkoff, Marc D, additional, McKendry, Christopher, additional, Metter, E Jeffrey, additional, and Alexandrov, Andrei V, additional

Published
2021
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43. High-resolution CT with arch/neck/head CT angiography on a mobile stroke unit.

Author

Alexandrov, Anne W., Arthur, Adam S., Bryndziar, Tomas, Swatzell, Victoria M., Dusenbury, Wendy, Hardage, Keri, McCormick, Sarah, Rhudy, James P., Maleki, Ana Hossein Zadeh, Singh, Savdeep, Krishnaiah, Balaji, Nearing, Katherine, Rubin, Mark N., Malkoff, Marc D., McKendry, Christopher, Metter, E. Jeffrey, and Alexandrov, Andrei V.

Subjects
NECK radiography, CRANIAL radiography, COMPUTERS in medicine, BLOOD vessels, SCIENTIFIC observation, HEMORRHAGIC stroke, TRANSIENT ischemic attack, INFARCTION, MOBILE hospitals, DIAGNOSTIC imaging, STROKE units, SUBARACHNOID hemorrhage, COMPUTED tomography, LONGITUDINAL method, DISEASE risk factors
Abstract

Background Mobile stroke units (MSUs) performance dependability and diagnostic yield of 16-slice, ultrafast CT with auto-injection angiography (CTA) of the aortic arch/neck/circle of Willis has not been previously reported. Methods We performed a prospective observational study of the first-of-its kind MSU equipped with high resolution, 16-slice CT with multiphasic CTA. Field CT/CTA was performed on all suspected stroke patients regardless of symptom severity or resolution. Performance dependability, efficiency and diagnostic yield over 365 days was quantified. Results 1031 MSU emergency activations occurred; of these, 629 (61%) were disregarded with unrelated diagnoses, and 402 patients transported: 245 (61%) ischemic or hemorrhagic stroke, 17 (4%) transient ischemic attack, 140 (35%) other neurologic emergencies. Total time from non-contrast CT/CTA start to images ready for viewing was 4.0 (IQR 3.5-4.5) min. Hemorrhagic stroke totaled 24 (10%): aneurysmal subarachnoid hemorrhage 3, hemorrhagic infarct 1, and 20 intraparenchymal hemorrhages (median intracerebral hemorrhage score was 2 (IQR 1-3), 4 (20%) spot sign positive). In 221 patients with ischemic stroke, 73 (33%) received alteplase with 31.5% treated within 60 min of onset. CTA revealed large vessel occlusion in 66 patients (30%) of which 9 (14%) were extracranial; 27 (41%) underwent thrombectomy with onset to puncture time averaging 141±90 min (median 112 (IQR 90-139) min) with full emergency department (ED) bypass. No imaging needed to be repeated for image quality; all patients were triaged correctly with no inter-hospital transfer required. Conclusions MSU use of advanced imaging including multiphasic head/neck CTA is feasible, offers high LVO yield and enables full ED bypass. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Tofacitinib inhibits inflammatory cytokines from ulcerative colitis and healthy mucosal explants and is associated with pSTAT1/3 reduction in T-cells

Author

Brand, Rhonda M., primary, Moore, Beverley A., additional, Zyhowski, Ashley, additional, Siegel, Aaron, additional, Uttam, Shikhar, additional, Metter, E. Jeffrey, additional, Engstrom, Jarret, additional, Brand, Randall E., additional, Biswas, Nabanita, additional, Whitcomb, David C., additional, Binion, David G., additional, Schwartz, Marc, additional, and McGowan, Ian, additional

Published
2021
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