Search

Your search keyword '"Albanes Demetrius"' showing total 3,544 results
Start Over Author "Albanes Demetrius"
3,544 results on '"Albanes Demetrius"'

1. Identification of pre-diagnostic lipid sets associated with liver cancer risk using untargeted lipidomics and chemical set analysis: A nested case-control study within the ATBC cohort.

Author

Barupal, Dinesh, Ramos, Mark, Florio, Andrea, Wheeler, William, Weinstein, Stephanie, Albanes, Demetrius, Graubard, Barry, Petrick, Jessica, McGlynn, Katherine, and Fiehn, Oliver

Subjects
ATBC study, ChemRICH, ceramides, lipidomics, liver cancer, metabolic reprogramming, Humans, Lipidomics, Case-Control Studies, Stearoyl-CoA Desaturase, Gas Chromatography-Mass Spectrometry, Liver Neoplasms, Fatty Acids, Unsaturated, Fatty Acids, Monounsaturated, Triglycerides
Abstract

In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR)

Published
2024

3. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex, Saunders, Edward, Chen, Fei, Janivara, Rohini, Darst, Burcu, Sheng, Xin, Xu, Yili, Chou, Alisha, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark, Plym, Anna, Sahimi, Ali, Hoffman, Thomas, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy, Schleutker, Johanna, Tammela, Teuvo, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham, Southey, Melissa, MacInnis, Robert, Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher, Cho, Kelly, Mcmahon, Benjamin, Neal, David, Donovan, Jenny, Hamdy, Freddie, Martin, Richard, Nordestgaard, Borge, Nielsen, Sune, Weischer, Maren, Bojesen, Stig, Røder, Andreas, Stroomberg, Hein, Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith, Tilly, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison, Ghoussaini, Maya, Travis, Ruth, Key, Tim, Riboli, Elio, Park, Jong, Sellers, Thomas, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael, Mucci, Lorelei, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David, Penney, Kathryn, Turman, Constance, Tangen, Catherine, Goodman, Phyllis, Thompson, Ian, Hamilton, Robert, Fleshner, Neil, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet, Ostrander, Elaine, Koutros, Stella, Beane Freeman, Laura, Stampfer, Meir, Wolk, Alicja, and Håkansson, Niclas

Subjects
Humans, Male, Black People, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Factors, White People, Asian People
Abstract

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Published
2023

4. Genome-wide interaction analysis of folate for colorectal cancer risk.

Author

Bouras, Emmanouil, Kim, Andre, Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth, Baurley, James, Berndt, Sonja, Bien, Stephanie, Bishop, Timothy, Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng, Chan, Andrew, Chang-Claude, Jenny, Conti, David, Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane, Giles, Graham, Gruber, Stephen, Gunter, Marc, Harrison, Tabitha, Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen, Joshi, Amit, Kawaguchi, Eric, Keku, Temitope, Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan, Li, Li, Lynch, Brigid, Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly, Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie, Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew, Peoples, Anita, Platz, Elizabeth, Potter, John, Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori, Schmit, Stephanie, Shcherbina, Anna, Stern, Mariana, Su, Yu-Ru, Tangen, Catherine, Thomas, Duncan, Tian, Yu, Um, Caroline, van Duijnhoven, Franzel, Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael, Ulrich, Cornelia, Hsu, Li, Gauderman, W, Peters, Ulrike, and Tsilidis, Konstantinos

Subjects
CRC, European, GWIS, SYN2, TIMP4, colorectal cancer, folate, folic acid, genome-wide, interaction, synapsin, tissue inhibitor of metalloproteinase 4, Humans, Folic Acid, Risk Factors, Colorectal Neoplasms, Case-Control Studies, Dietary Supplements
Abstract

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folates role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Published
2023

5. Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.

Author

Canzian, Federico, Du, Mengmeng, Gallinger, Steven, Giles, Graham, Goodman, Phyllis, Haiman, Christopher, Kogevinas, Manolis, Kooperberg, Charles, LeMarchand, Loic, Neale, Rachel, Visvanathan, Kala, White, Emily, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Berndt, Sonja, Brais, Lauren, Brennan, Paul, Buring, Julie, Rabe, Kari, Bamlet, William, Chanock, Stephen, Fuchs, Charles, Gaziano, J, Giovannucci, Edward, Hackert, Thilo, Hassan, Manal, Katzke, Verena, Kurtz, Robert, Lee, I-Min, Malats, Núria, Murphy, Neil, Oberg, Ann, Orlow, Irene, Porta, Miquel, Real, Francisco, Rothman, Nathaniel, Sesso, Howard, Silverman, Debra, Thompson, Ian, Wactawski-Wende, Jean, Wang, Xiaoliang, Wentzensen, Nicolas, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Yu, Kai, Wolpin, Brian, Duell, Eric, Li, Donghui, Hung, Rayjean, Perdomo, Sandra, McCullough, Marjorie, Freedman, Neal, Patel, Alpa, Peters, Ulrike, Riboli, Elio, Sund, Malin, Tjønneland, Anne, Zhong, Jun, Van Den Eeden, Stephen, Kraft, Peter, Risch, Harvey, Amundadottir, Laufey, Klein, Alison, Stolzenberg-Solomon, Rachael, Antwi, Samuel, King, Sontoria, Veliginti, Swathi, Brouwers, Martijn, Ren, Zhewen, Zheng, Wei, Setiawan, Veronica, Wilkens, Lynne, Shu, Xiao-Ou, Arslan, Alan, Beane Freeman, Laura, and Bracci, Paige

Subjects
Humans, Non-alcoholic Fatty Liver Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Mendelian Randomization Analysis, Pancreatic Neoplasms, Obesity, Polymorphism, Single Nucleotide
Abstract

BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.

Published
2023

7. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author

Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei

Published
2024
Full Text
View/download PDF

12. Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis.

Author

Rhee, Jongeun, Birmann, Brenda, De Roos, Anneclaire, Epstein, Mara, Martinez-Maza, Otoniel, Breen, Elizabeth, Magpantay, Larry, Levin, Lynn, Visvanathan, Kala, Hosgood, H, Rohan, Thomas, Smoller, Sylvia, Bassig, Bryan, Qi, Lihong, Shu, Xiao-Ou, Koh, Woon-Puay, Zheng, Wei, Yuan, Jian-Min, Weinstein, Stephanie, Albanes, Demetrius, Lan, Qing, Rothman, Nathaniel, and Purdue, Mark

Subjects
CXCL13, immune markers, non-Hodgkin lymphoma, sCD27, sCD30, Adult, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Biomarkers, Lymphoma, Large B-Cell, Diffuse, Case-Control Studies, Lymphoma, Mantle-Cell
Abstract

Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) have been associated with non-Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case-control studies to investigate subtype-specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (ORT3 ) = 2.2, 95% CI = 1.6-3.1], sCD30 (ORT3  = 2.0, 95% CI = 1.6-2.5) and CXCL13 (ORT3  = 2.3, 95% CI = 1.8-3.0). We also observed associations with sCD27 for CLL/SLL (ORT3  = 3.3, 95% CI = 2.4-4.6), MZL (ORT3  = 7.7, 95% CI = 3.0-20.1) and TCL (ORT3  = 3.4, 95% CI = 1.5-7.7), and between sCD30 and FL (ORT3  = 2.7, 95% CI = 2.0-3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27-TCL and all three DLBCL associations were equivalent across both follow-up periods (

Published
2023

14. Yoghurt Intake and Gastric Cancer: A Pooled Analysis of 16 Studies of the StoP Consortium

Author

Collatuzzo, Giulia, Negri, Eva, Pelucchi, Claudio, Bonzi, Rossella, Turati, Federica, Rabkin, Charles S, Liao, Linda M, Sinha, Rashmi, Palli, Domenico, Ferraroni, Monica, López-Carrillo, Lizbeth, Lunet, Nuno, Morais, Samantha, Albanes, Demetrius, Weinstein, Stephanie J, Parisi, Dominick, Zaridze, David, Maximovitch, Dmitry, Dierssen-Sotos, Trinidad, Jiménez-Moleón, José Juan, Vioque, Jesus, de la Hera, Manoli Garcia, Curado, Maria Paula, Dias-Neto, Emmanuel, Hernández-Ramírez, Raúl Ulises, López-Cervantes, Malaquias, Ward, Mary H, Tsugane, Shoichiro, Hidaka, Akihisa, Lagiou, Areti, Lagiou, Pagona, Zhang, Zuo-Feng, Trichopoulou, Antonia, Karakatsani, Anna, Camargo, Maria Constanza, La Vecchia, Carlo, and Boffetta, Paolo

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Cancer, Digestive Diseases, Oral and gastrointestinal, Male, Humans, Female, Stomach Neoplasms, Case-Control Studies, Logistic Models, Adenocarcinoma, Helicobacter Infections, Risk Factors, gastric cancer, diet, nutrition, yoghurt, Food Sciences, Nutrition and Dietetics, Clinical sciences, Nutrition and dietetics, Public health
Abstract

BackgroundYoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC).MethodsWe pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted.ResultsThe analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women.ConclusionsWe found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Published
2023

15. Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Author

Shi, Jianxin, Shiraishi, Kouya, Choi, Jiyeon, Matsuo, Keitaro, Chen, Tzu-Yu, Dai, Juncheng, Hung, Rayjean J, Chen, Kexin, Shu, Xiao-Ou, Kim, Young Tae, Landi, Maria Teresa, Lin, Dongxin, Zheng, Wei, Yin, Zhihua, Zhou, Baosen, Song, Bao, Wang, Jiucun, Seow, Wei Jie, Song, Lei, Chang, I-Shou, Hu, Wei, Chien, Li-Hsin, Cai, Qiuyin, Hong, Yun-Chul, Kim, Hee Nam, Wu, Yi-Long, Wong, Maria Pik, Richardson, Brian Douglas, Funderburk, Karen M, Li, Shilan, Zhang, Tongwu, Breeze, Charles, Wang, Zhaoming, Blechter, Batel, Bassig, Bryan A, Kim, Jin Hee, Albanes, Demetrius, Wong, Jason YY, Shin, Min-Ho, Chung, Lap Ping, Yang, Yang, An, She-Juan, Zheng, Hong, Yatabe, Yasushi, Zhang, Xu-Chao, Kim, Young-Chul, Caporaso, Neil E, Chang, Jiang, Ho, James Chung Man, Kubo, Michiaki, Daigo, Yataro, Song, Minsun, Momozawa, Yukihide, Kamatani, Yoichiro, Kobayashi, Masashi, Okubo, Kenichi, Honda, Takayuki, Hosgood, Dean H, Kunitoh, Hideo, Patel, Harsh, Watanabe, Shun-ichi, Miyagi, Yohei, Nakayama, Haruhiko, Matsumoto, Shingo, Horinouchi, Hidehito, Tsuboi, Masahiro, Hamamoto, Ryuji, Goto, Koichi, Ohe, Yuichiro, Takahashi, Atsushi, Goto, Akiteru, Minamiya, Yoshihiro, Hara, Megumi, Nishida, Yuichiro, Takeuchi, Kenji, Wakai, Kenji, Matsuda, Koichi, Murakami, Yoshinori, Shimizu, Kimihiro, Suzuki, Hiroyuki, Saito, Motonobu, Ohtaki, Yoichi, Tanaka, Kazumi, Wu, Tangchun, Wei, Fusheng, Dai, Hongji, Machiela, Mitchell J, Su, Jian, Kim, Yeul Hong, Oh, In-Jae, Lee, Victor Ho Fun, Chang, Gee-Chen, Tsai, Ying-Huang, Chen, Kuan-Yu, Huang, Ming-Shyan, Su, Wu-Chou, Chen, Yuh-Min, Seow, Adeline, Park, Jae Yong, and Kweon, Sun-Seog

Subjects
Genetics, Cancer, Clinical Research, Human Genome, Prevention, Lung, Lung Cancer, Tobacco, Tobacco Smoke and Health, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Adenocarcinoma of Lung, Asia, Eastern, Lung Neoplasms, Polymorphism, Single Nucleotide
Abstract

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Published
2023

16. Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score

Author

Huynh-Le, Minh-Phuong, Karunamuni, Roshan, Fan, Chun Chieh, Asona, Lui, Thompson, Wesley K, Martinez, Maria Elena, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth R, Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E, Nordestgaard, Børge G, Tangen, Catherine M, MacInnis, Robert J, Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A, Travis, Ruth C, Blot, William J, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Nielsen, Sune F, Kibel, Adam S, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Rosenstein, Barry S, Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L, Huff, Chad D, Teixeira, Manuel R, Multigner, Luc, Leach, Robin J, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, De Ruyck, Kim, Ost, Piet, Razack, Azad, Newcomb, Lisa F, Fowke, Jay H, Gamulin, Marija, Abraham, Aswin, Claessens, Frank, Castelao, Jose Esteban, Townsend, Paul A, Crawford, Dana C, Petrovics, Gyorgy, van Schaik, Ron HN, Parent, Marie-Élise, Hu, Jennifer J, Zheng, Wei, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, and Seibert, Tyler M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Prevention, Genetics, Good Health and Well Being, Male, Humans, Prostate-Specific Antigen, Prostatic Neoplasms, Early Detection of Cancer, Polymorphism, Single Nucleotide, Risk Factors, Risk Assessment, Genetic Predisposition to Disease, UKGPCS collaborators, APCB, NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

Published
2022

17. Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.

Author

Byun, Jinyoung, Han, Younghun, Li, Yafang, Xia, Jun, Long, Erping, Choi, Jiyeon, Xiao, Xiangjun, Zhu, Meng, Zhou, Wen, Sun, Ryan, Bossé, Yohan, Song, Zhuoyi, Schwartz, Ann, Lusk, Christine, Rafnar, Thorunn, Stefansson, Kari, Zhang, Tongwu, Zhao, Wei, Pettit, Rowland W, Liu, Yanhong, Li, Xihao, Zhou, Hufeng, Walsh, Kyle M, Gorlov, Ivan, Gorlova, Olga, Zhu, Dakai, Rosenberg, Susan M, Pinney, Susan, Bailey-Wilson, Joan E, Mandal, Diptasri, de Andrade, Mariza, Gaba, Colette, Willey, James C, You, Ming, Anderson, Marshall, Wiencke, John K, Albanes, Demetrius, Lam, Stephan, Tardon, Adonina, Chen, Chu, Goodman, Gary, Bojeson, Stig, Brenner, Hermann, Landi, Maria Teresa, Chanock, Stephen J, Johansson, Mattias, Muley, Thomas, Risch, Angela, Wichmann, H-Erich, Bickeböller, Heike, Christiani, David C, Rennert, Gad, Arnold, Susanne, Field, John K, Shete, Sanjay, Le Marchand, Loic, Melander, Olle, Brunnstrom, Hans, Liu, Geoffrey, Andrew, Angeline S, Kiemeney, Lambertus A, Shen, Hongbing, Zienolddiny, Shanbeh, Grankvist, Kjell, Johansson, Mikael, Caporaso, Neil, Cox, Angela, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B, Aldrich, Melinda C, Patel, Alpa, Lan, Qing, Rothman, Nathaniel, Taylor, Fiona, Kachuri, Linda, Witte, John S, Sakoda, Lori C, Spitz, Margaret, Brennan, Paul, Lin, Xihong, McKay, James, Hung, Rayjean J, and Amos, Christopher I

Subjects
Humans, Lung Neoplasms, Genetic Predisposition to Disease, RNA-Binding Proteins, DNA-Binding Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Human Genome, Cancer, Genetics, Lung, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.

Published
2022

18. Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer

Author

Papadimitriou, Nikos, Kim, Andre, Kawaguchi, Eric S., Morrison, John, Diez-Obrero, Virginia, Albanes, Demetrius, Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D Timothy, Bouras, Emmanouil, Brenner, Hermann, Buchanan, Daniel D., Campbell, Peter T., Carreras-Torres, Robert, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Devall, Matthew A., Dimou, Niki, Drew, David A., Gruber, Stephen B., Harrison, Tabitha A., Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Keku, Temitope O., Kundaje, Anshul, Küry, Sébastien, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Moreno, Victor, Newton, Christina C., Obón-Santacana, Mireia, Ose, Jennifer, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Thomas, Duncan C., Thomas, Claire E., Tian, Yu, Tsilidis, Konstantinos K., Ulrich, Cornelia M., Um, Caroline Y., Visvanathan, Kala, Wang, Jun, White, Emily, Woods, Michael O., Schmit, Stephanie L., Macrae, Finlay, Potter, John D., Hopper, John L., Peters, Ulrike, Murphy, Neil, Hsu, Li, Gunter, Marc J., and Gauderman, W. James

Published
2024
Full Text
View/download PDF

20. Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study

Author

Papadimitriou, Nikos, Bull, Caroline J., Jenab, Mazda, Hughes, David J., Bell, Joshua A., Sanderson, Eleanor, Timpson, Nicholas J., Smith, George Davey, Albanes, Demetrius, Campbell, Peter T., Küry, Sébastien, Le Marchand, Loic, Ulrich, Cornelia M., Visvanathan, Kala, Figueiredo, Jane C., Newcomb, Polly A., Pai, Rish K., Peters, Ulrike, Tsilidis, Kostas K., Boer, Jolanda M. A., Vincent, Emma E., Mariosa, Daniela, Gunter, Marc J., Richardson, Tom G., and Murphy, Neil

Published
2023
Full Text
View/download PDF

23. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis

Author

Landi, Maria Teresa, Stevens, Victoria, Wang, Ying, Albanes, Demetrios, Caporaso, Neil, Brennan, Paul, Amos, Christopher I., Shete, Sanjay, Hung, Rayjean J., Bickeböller, Heike, Risch, Angela, Houlston, Richard, Lam, Stephen, Tardon, Adonina, Chen, Chu, Bojesen, Stig E., Johansson, Mattias, Wichmann, H-Erich, Christiani, David, Rennert, Gadi, Arnold, Susanne, Field, John K., Le Marchand, Loic, Melander, Olle, Brunnström, Hans, Liu, Geoffrey, Andrew, Angeline, Kiemeney, Lambertus A., Shen, Hongbing, Zienolddiny, Shan, Grankvist, Kjell, Johansson, Mikael, Teare, M. Dawn, Hong, Yun-Chul, Yuan, Jian-Min, Lazarus, Philip, Schabath, Matthew B., Aldrich, Melinda C., Eeles, Rosalind A., Haiman, Christopher A., Kote-Jarai, Zsofia, Schumacher, Fredrick R., Benlloch, Sara, Al Olama, Ali Amin, Muir, Kenneth R., Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Tangen, Catherine M., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie J., Wolk, Alicja, West, Catharine M.L., Mucci, Lorelei A., Cancel-Tassin, Géraldine, Koutros, Stella, Sørensen, Karina Dalsgaard, Grindedal, Eli Marie, Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Ingles, Sue Ann, Rosenstein, Barry S., Lu, Yong-Jie, Giles, Graham G., MacInnis, Robert J., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanfrod, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Nielsen, Sune F., Brenner, Hermann, Maier, Christiane, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Castelao, Jose Esteban, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Kraft, Peter, Blot, William J., Riboli, Elio, Yarmolinsky, James, Robinson, Jamie W., Mariosa, Daniela, Karhunen, Ville, Huang, Jian, Dimou, Niki, Murphy, Neil, Burrows, Kimberley, Bouras, Emmanouil, Smith-Byrne, Karl, Lewis, Sarah J., Galesloot, Tessel E., Vermeulen, Sita, Martin, Paul, Hou, Lifang, Newcomb, Polly A., White, Emily, Wu, Anna H., Le Marchand, Loïc, Phipps, Amanda I., Buchanan, Daniel D., Zhao, Sizheng Steven, Gill, Dipender, Chanock, Stephen J., Purdue, Mark P., Davey Smith, George, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Amos, Chris I., Dehghan, Abbas, Gunter, Marc J., Tsilidis, Kostas K., and Martin, Richard M.

Published
2024
Full Text
View/download PDF

25. Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies

Author

Sidahmed, Elkhansa, Freedland, Stephen J., Wang, Molin, Wu, Kana, Albanes, Demetrius, Barnett, Matt, van den Brandt, Piet A., Cook, Michael B., Giles, Graham G., Giovannucci, Edward, Haiman, Christopher A., Larsson, Susanna C., Key, Timothy J., Loftfield, Erikka, Männistö, Satu, McCullough, Marjorie L., Milne, Roger L., Neuhouser, Marian L., Platz, Elizabeth A., Perez-Cornago, Aurora, Sawada, Norie, Schenk, Jeannette M., Sinha, Rashmi, Tsugane, Shoichiro, Visvanathan, Kala, Wang, Ying, White, Kami K., Willett, Walter C., Wolk, Alicja, Ziegler, Regina G., Genkinger, Jeanine M., and Smith-Warner, Stephanie A.

Published
2024
Full Text
View/download PDF

26. Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study

Author

Tsilidis, Konstantinos K, Papadimitriou, Nikos, Dimou, Niki, Gill, Dipender, Lewis, Sarah J, Martin, Richard M, Murphy, Neil, Markozannes, Georgios, Zuber, Verena, Cross, Amanda J, Burrows, Kimberley, Lopez, David S, Key, Timothy J, Travis, Ruth C, Perez-Cornago, Aurora, Hunter, David J, van Duijnhoven, Fränzel JB, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Boehm, Juergen, Brenner, Hermann, Burnett-Hartman, Andrea, Campbell, Peter T, Casey, Graham, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, de la Chapelle, Albert, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Goodman, Phyllis J, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Hoffmeister, Michael, Jenkins, Mark A, Keku, Temitope O, Kweon, Sun-Seog, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Martín, Vicente, Milne, Roger L, Moreno, Victor, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul DP, Platz, Elizabeth A, Potter, John D, Qi, Lihong, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Slattery, Martha L, Snetselaar, Linda, Schenk, Jeanette, Thibodeau, Stephen N, Ulrich, Cornelia M, Van Guelpen, Bethany, Harlid, Sophia, Visvanathan, Kala, Vodickova, Ludmila, Wang, Hansong, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zheng, Wei, Bueno-de-Mesquita, Bas, Boutron-Ruault, Marie-Christine, Hughes, David J, Jakszyn, Paula, Kühn, Tilman, Palli, Domenico, Riboli, Elio, Giovannucci, Edward L, Banbury, Barbara L, Gruber, Stephen B, Peters, Ulrike, Gunter, Marc J, and on behalf of GECCO, CORECT

Subjects
Complementary and Integrative Health, Digestive Diseases, Clinical Research, Clinical Trials and Supportive Activities, Cancer, Colo-Rectal Cancer, Prevention, Nutrition, Prevention of disease and conditions, and promotion of well-being, 3.3 Nutrition and chemoprevention, Case-Control Studies, Colorectal Neoplasms, Dietary Supplements, Genetic Predisposition to Disease, Humans, Mendelian Randomization Analysis, Micronutrients, Risk Factors, Selenium, Vitamin B 12, White People, Mendelian randomization, genes, nutrition, supplements, colorectal cancer, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

Published
2021

27. Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Author

Karunamuni, Roshan A, Huynh-Le, Minh-Phuong, Fan, Chun C, Thompson, Wesley, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, Lophatananon, Artitaya, UKGPCS collaborators, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, APCB BioResource (Australian Prostate Cancer BioResource), Grönberg, Henrik, Walsh, Eleanor I, Turner, Emma L, Lane, Athene, Martin, Richard M, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Nordestgaard, Børge G, Tangen, Catherine M, MacInnis, Robert J, Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A, Travis, Ruth C, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Nielsen, Sune F, Kibel, Adam S, Wiklund, Fredrik, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Rosenstein, Barry S, Vega, Ana, IMPACT Study Steering Committee and Collaborators, Kogevinas, Manolis, Penney, Kathryn L, Teixeira, Manuel R, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, Razack, Azad, Newcomb, Lisa F, Canary PASS Investigators, Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A, Roobol, Monique J, Zheng, Wei, Profile Study Steering Committee, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, and PRACTICAL Consortium

Subjects
UKGPCS collaborators, APCB BioResource, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Prevention, Urologic Diseases, Cancer, Prostate Cancer, Aging, Urology & Nephrology, Oncology and Carcinogenesis
Abstract

BackgroundPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).Materials and method180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.Results166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.ConclusionsIncorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

Published
2021

28. A mechanistic basis for amplification differences between samples and between genome regions

Author

Veal Colin D, Freeman Peter J, Jacobs Kevin, Lancaster Owen, Jamain Stéphane, Leboyer Marion, Albanes Demetrius, Vaghela Reshma R, Gut Ivo, Chanock Stephen J, and Brookes Anthony J

Subjects
DNA amplification, DNA denaturation, C + G, Illumina infinium, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background For many analytical methods the efficiency of DNA amplification varies across the genome and between samples. The most affected genome regions tend to correlate with high C + G content, however this relationship is complex and does not explain why the direction and magnitude of effects varies considerably between samples. Results Here, we provide evidence that sequence elements that are particularly high in C + G content can remain annealed even when aggressive melting conditions are applied. In turn, this behavior creates broader ‘Thermodynamically Ultra-Fastened’ (TUF) regions characterized by incomplete denaturation of the two DNA strands, so reducing amplification efficiency throughout these domains. Conclusions This model provides a mechanistic explanation for why some genome regions are particularly difficult to amplify and assay in many procedures, and importantly it also explains inter-sample variability of this behavior. That is, DNA samples of varying quality will carry more or fewer nicks and breaks, and hence their intact TUF regions will have different lengths and so be differentially affected by this amplification suppression mechanism – with ‘higher’ quality DNAs being the most vulnerable. A major practical consequence of this is that inter-region and inter-sample variability can be largely overcome by employing routine fragmentation methods (e.g. sonication or restriction enzyme digestion) prior to sample amplification.

Published
2012
Full Text
View/download PDF

29. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Author

Huynh-Le, Minh-Phuong, Fan, Chun Chieh, Karunamuni, Roshan, Thompson, Wesley K, Martinez, Maria Elena, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nielsen, Sune F, Nordestgaard, Børge G, Wiklund, Fredrik, Tangen, Catherine M, Giles, Graham G, Wolk, Alicja, Albanes, Demetrius, Travis, Ruth C, Blot, William J, Zheng, Wei, Sanderson, Maureen, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Kibel, Adam S, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Khaw, Kay-Tee, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Thibodeau, Stephen N, Rosenstein, Barry S, Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L, Huff, Chad, Teixeira, Manuel R, Multigner, Luc, Leach, Robin J, Cannon-Albright, Lisa, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, De Ruyck, Kim, Pandha, Hardev, Razack, Azad, Newcomb, Lisa F, Fowke, Jay H, Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A, Bush, William S, Roobol, Monique J, Parent, Marie-Élise, Hu, Jennifer J, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, and PRACTICAL Consortium

Subjects
UKGPCS collaborators, APCB, NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Humans, Prostatic Neoplasms, Neoplasm Invasiveness, Multivariate Analysis, Multifactorial Inheritance, Aged, Middle Aged, Ethnic Groups, Male, Self Report, Aging, Urologic Diseases, Cancer, Prostate Cancer
Abstract

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p

Published
2021

31. A prospective study of physical activity and the risk of pancreatic cancer among women (United States)

Author

Schairer Catherine, Schatzkin Arthur, Moore Steven C, Stolzenberg-Solomon Rachael Z, Calton Brook A, Albanes Demetrius, and Leitzmann Michael F

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Several epidemiologic studies have examined the association between physical activity and pancreatic cancer risk; however, the results of these studies are not consistent. Methods This study examined the associations of total, moderate, and vigorous physical activity to pancreatic cancer in a cohort of 33,530 U.S. women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP). At baseline (1987–1989), information on physical activity over the past year was obtained using a self-administered questionnaire. Cox proportional hazards regression was used to estimate relative risks (RR) and 95% confidence intervals of pancreatic cancer risk. Results 70 incident cases of pancreatic cancer were ascertained during 284,639 person years of follow-up between 1987–1989 and 1995–1998. After adjustment for age, body mass index, smoking status, history of diabetes, and height, increased physical activity was related to a suggestively decreased risk of pancreatic cancer. The RRs for increasing quartiles of total physical activity were 1.0, 0.80, 0.66, 0.52 (95% CI = 0.26, 1.05; ptrend = 0.05). This association was consistent across subgroups defined by body mass index and smoking status. We also observed statistically non-significant reductions in pancreatic cancer risk for women in the highest quartile of moderate (RR = 0.57; 95% CI = 0.26, 1.26) and highest quartile of vigorous physical activity (RR = 0.63; 95% CI = 0.31, 1.28) compared to their least active counterparts. Conclusion Our study provides evidence for a role of physical activity in protecting against pancreatic cancer.

Published
2008
Full Text
View/download PDF

32. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author

Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike

Published
2023
Full Text
View/download PDF

33. Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Author

Berndt, Sonja I., Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J., Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E., Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F., Morton, Lindsay M., Brooks-Wilson, Angela R., Teras, Lauren R., Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C., Ansell, Stephen M., Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M., Boffetta, Paolo, Bracci, Paige M., Brennan, Paul, Brown, Elizabeth E., Burdett, Laurie, Cannon-Albright, Lisa A., Chang, Ellen T., Chiu, Brian C. H., Chung, Charles C., Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V., Cox, David G., Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W. Ryan, Dogan, Ahmet, Edlund, Christopher K., Foretova, Lenka, Fraumeni, Jr, Joseph F., Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G., Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M., Haiman, Christopher A., Haioun, Corinne, Hofmann, Jonathan N., Holford, Theodore R., Holly, Elizabeth A., Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D., Jarrett, Ruth F., Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N., Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K., Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L., Molina, Thierry J., Monnereau, Alain, Montalvan, Rebecca, North, Kari E., Novak, Anne J., Onel, Kenan, Purdue, Mark P., Rand, Kristin A., Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W., Severson, Richard K., Shanafelt, Tait D., Smith, Martyn T., Smith, Alexandra, Song, Kevin W., Song, Lei, Southey, Melissa C., Spinelli, John J., Staines, Anthony, Stephens, Deborah, Sutherland, Heather J., Tkachuk, Kaitlyn, Thompson, Carrie A., Tilly, Hervé, Tinker, Lesley F., Travis, Ruth C., Turner, Jenny, Vachon, Celine M., Vajdic, Claire M., Van Den Berg, Anke, Van Den Berg, David J., Vermeulen, Roel C. H., Vineis, Paolo, Wang, Sophia S., Weiderpass, Elisabete, Weiner, George J., Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R., Chanock, Stephen J., Slager, Susan L., and Rothman, Nathaniel

Published
2022
Full Text
View/download PDF

35. Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights

Author

Koutros, Stella, Kiemeney, Lambertus A., Pal Choudhury, Parichoy, Milne, Roger L., Lopez de Maturana, Evangelina, Ye, Yuanqing, Joseph, Vijai, Florez-Vargas, Oscar, Dyrskjøt, Lars, Figueroa, Jonine, Dutta, Diptavo, Giles, Graham G., Hildebrandt, Michelle A.T., Offit, Kenneth, Kogevinas, Manolis, Weiderpass, Elisabete, McCullough, Marjorie L., Freedman, Neal D., Albanes, Demetrius, Kooperberg, Charles, Cortessis, Victoria K., Karagas, Margaret R., Johnson, Alison, Schwenn, Molly R., Baris, Dalsu, Furberg, Helena, Bajorin, Dean F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Benhamou, Simone, Kraft, Peter, Porru, Stefano, Carta, Angela, Bishop, Timothy, Southey, Melissa C., Matullo, Giuseppe, Fletcher, Tony, Kumar, Rajiv, Taylor, Jack A., Lamy, Philippe, Prip, Frederik, Kalisz, Mark, Weinstein, Stephanie J., Hengstler, Jan G., Selinski, Silvia, Harland, Mark, Teo, Mark, Kiltie, Anne E., Tardón, Adonina, Serra, Consol, Carrato, Alfredo, García-Closas, Reina, Lloreta, Josep, Schned, Alan, Lenz, Petra, Riboli, Elio, Brennan, Paul, Tjønneland, Anne, Otto, Thomas, Ovsiannikov, Daniel, Volkert, Frank, Vermeulen, Sita H., Aben, Katja K., Galesloot, Tessel E., Turman, Constance, De Vivo, Immaculata, Giovannucci, Edward, Hunter, David J., Hohensee, Chancellor, Hunt, Rebecca, Patel, Alpa V., Huang, Wen-Yi, Thorleifsson, Gudmar, Gago-Dominguez, Manuela, Amiano, Pilar, Golka, Klaus, Stern, Mariana C., Yan, Wusheng, Liu, Jia, Li, Shengchao Alfred, Katta, Shilpa, Hutchinson, Amy, Hicks, Belynda, Wheeler, William A., Purdue, Mark P., McGlynn, Katherine A., Kitahara, Cari M., Haiman, Christopher A., Greene, Mark H., Rafnar, Thorunn, Chatterjee, Nilanjan, Chanock, Stephen J., Wu, Xifeng, Real, Francisco X., Silverman, Debra T., Garcia-Closas, Montserrat, Stefansson, Kari, Prokunina-Olsson, Ludmila, Malats, Núria, and Rothman, Nathaniel

Published
2023
Full Text
View/download PDF

36. The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study

Author

Albanes Demetrius, Clevidence Beverly, Hartman Terryl J, Brown Ellen, Campbell William, Dorgan Joanne F, Johnson Laura L, Baer David J, Mahabir Somdat, Judd Joseph T, and Taylor Philip R

Subjects
Alcohol, Hormones, Postmenopausal women, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. Methods Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. Results and Discussion At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels. Conclusions These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.

Published
2004
Full Text
View/download PDF

37. Food and nutrient intake in relation to mental wellbeing

Author

Albanes Demetrius, Virtamo Jarmo, Haukka Jari, Partonen Timo, Hakkarainen Reeta, and Lönnqvist Jouko

Subjects
anxiety, depression, food, insomnia, nutrition, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background We studied food consumption and nutrient intake in subjects with depressed mood, anxiety and insomnia as indices of compromised mental wellbeing. Methods The study population consisted of 29,133 male smokers aged 50 to 69 years who entered the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in 1985–1988. This was a placebo-controlled trial to test whether supplementation with alpha-tocopherol or beta-carotene prevents lung cancer. At baseline 27,111 men completed a diet history questionnaire from which food and alcohol consumption and nutrient intake were calculated. The questionnaire on background and medical history included three symptoms on mental wellbeing, anxiety, depression and insomnia experienced in the past four months. Results Energy intake was higher in men who reported anxiety or depressed mood, and those reporting any such symptoms consumed more alcohol. Subjects reporting anxiety or depressed mood had higher intake of omega-3 fatty acids and omega-6 fatty acids. Conclusions Our findings conflict with the previous reports of beneficial effects of omega-3 fatty acids on mood.

Published
2004
Full Text
View/download PDF

38. Functional informed genome‐wide interaction analysis of body mass index, diabetes and colorectal cancer risk

Author

Xia, Zhiyu, Su, Yu‐Ru, Petersen, Paneen, Qi, Lihong, Kim, Andre E, Figueiredo, Jane C, Lin, Yi, Nan, Hongmei, Sakoda, Lori C, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bien, Stephanie, Buchanan, Daniel D, Casey, Graham, Chan, Andrew T, Conti, David V, Drew, David A, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Gruber, Stephen B, Gunter, Marc J, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Le Marchand, Loic, Lewinger, Juan P, Li, Li, Lindor, Noralane M, Moreno, Victor, Murphy, Neil, Nassir, Rami, Newcomb, Polly A, Ogino, Shuji, Rennert, Gad, Song, Mingyang, Wang, Xiaoliang, Wolk, Alicja, Woods, Michael O, Brenner, Hermann, White, Emily, Slattery, Martha L, Giovannucci, Edward L, Chang‐Claude, Jenny, Pharoah, Paul DP, Hsu, Li, Campbell, Peter T, and Peters, Ulrike

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Human Genome, Genetics, Cancer, Diabetes, Prevention, Nutrition, Colo-Rectal Cancer, Metabolic and endocrine, ATPases Associated with Diverse Cellular Activities, Aged, Body Mass Index, Colorectal Neoplasms, Databases, Genetic, Diabetes Mellitus, Type 2, Female, Gene Expression, Genotype, Hepatocyte Nuclear Factor 3-alpha, Humans, Male, Microtubule-Associated Proteins, Middle Aged, Obesity, Phenotype, Proteasome Endopeptidase Complex, Protein Tyrosine Phosphatase, Non-Receptor Type 2, Sex Factors, Sialic Acid Binding Ig-like Lectin 3, Voltage-Gated Sodium Channel beta-1 Subunit, BMI, colorectal cancer, diabetes, gene expression, gene-environmental interaction, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

BackgroundBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.MethodsTo improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR

Published
2020

39. Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility.

Author

Kachuri, Linda, Johansson, Mattias, Rashkin, Sara R, Graff, Rebecca E, Bossé, Yohan, Manem, Venkata, Caporaso, Neil E, Landi, Maria Teresa, Christiani, David C, Vineis, Paolo, Liu, Geoffrey, Scelo, Ghislaine, Zaridze, David, Shete, Sanjay S, Albanes, Demetrius, Aldrich, Melinda C, Tardón, Adonina, Rennert, Gad, Chen, Chu, Goodman, Gary E, Doherty, Jennifer A, Bickeböller, Heike, Field, John K, Davies, Michael P, Dawn Teare, M, Kiemeney, Lambertus A, Bojesen, Stig E, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Le Marchand, Loïc, Cheng, Iona, Schabath, Matthew B, Duell, Eric J, Andrew, Angeline S, Manjer, Jonas, Lazarus, Philip, Arnold, Susanne, McKay, James D, Emami, Nima C, Warkentin, Matthew T, Brhane, Yonathan, Obeidat, Ma'en, Martin, Richard M, Relton, Caroline, Davey Smith, George, Haycock, Philip C, Amos, Christopher I, Brennan, Paul, Witte, John S, and Hung, Rayjean J

Subjects
Lung, Humans, Lung Neoplasms, Genetic Predisposition to Disease, Respiratory Function Tests, Vital Capacity, Forced Expiratory Volume, Prospective Studies, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Female, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide
Abstract

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.

Published
2020

40. 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

44. Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program

Author

Robbins, Hilary A., Alcala, Karine, Moez, Elham Khodayari, Guida, Florence, Thomas, Sera, Zahed, Hana, Warkentin, Matthew T., Smith-Byrne, Karl, Brhane, Yonathan, Muller, David, Feng, Xiaoshuang, Albanes, Demetrius, Aldrich, Melinda C., Arslan, Alan A., Bassett, Julie, Berg, Christine D., Cai, Qiuyin, Chen, Chu, Davies, Michael P.A., Diergaarde, Brenda, Field, John K., Freedman, Neal D., Huang, Wen-Yi, Johansson, Mikael, Jones, Michael, Koh, Woon-Puay, Lam, Stephen, Lan, Qing, Langhammer, Arnulf, Liao, Linda M., Liu, Geoffrey, Malekzadeh, Reza, Milne, Roger L., Montuenga, Luis M., Rohan, Thomas, Sesso, Howard D., Severi, Gianluca, Sheikh, Mahdi, Sinha, Rashmi, Shu, Xiao-Ou, Stevens, Victoria L., Tammemägi, Martin C., Tinker, Lesley F., Visvanathan, Kala, Wang, Ying, Wang, Renwei, Weinstein, Stephanie J., White, Emily, Wilson, David, Yuan, Jian-Min, Zhang, Xuehong, Zheng, Wei, Amos, Christopher I., Brennan, Paul, Johansson, Mattias, and Hung, Rayjean J.

Published
2023
Full Text
View/download PDF

45. Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer

Author

Drew, David A., primary, Kim, Andre E., additional, Lin, Yi, additional, Qu, Conghui, additional, Morrison, John, additional, Lewinger, Juan Pablo, additional, Kawaguchi, Eric, additional, Wang, Jun, additional, Fu, Yubo, additional, Zemlianskaia, Natalia, additional, Díez-Obrero, Virginia, additional, Bien, Stephanie A., additional, Dimou, Niki, additional, Albanes, Demetrius, additional, Baurley, James W., additional, Wu, Anna H., additional, Buchanan, Daniel D., additional, Potter, John D., additional, Prentice, Ross L., additional, Harlid, Sophia, additional, Arndt, Volker, additional, Barry, Elizabeth L., additional, Berndt, Sonja I., additional, Bouras, Emmanouil, additional, Brenner, Hermann, additional, Budiarto, Arif, additional, Burnett-Hartman, Andrea, additional, Campbell, Peter T., additional, Carreras-Torres, Robert, additional, Casey, Graham, additional, Chang-Claude, Jenny, additional, Conti, David V., additional, Devall, Matthew A.M., additional, Figueiredo, Jane C., additional, Gruber, Stephen B., additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Harrison, Tabitha A., additional, Hidaka, Akihisa, additional, Hoffmeister, Michael, additional, Huyghe, Jeroen R., additional, Jenkins, Mark A., additional, Jordahl, Kristina M., additional, Kundaje, Anshul, additional, Le Marchand, Loic, additional, Li, Li, additional, Lynch, Brigid M., additional, Murphy, Neil, additional, Nassir, Rami, additional, Newcomb, Polly A., additional, Newton, Christina C., additional, Obón-Santacana, Mireia, additional, Ogino, Shuji, additional, Ose, Jennifer, additional, Pai, Rish K., additional, Palmer, Julie R., additional, Papadimitriou, Nikos, additional, Pardamean, Bens, additional, Pellatt, Andrew J., additional, Peoples, Anita R., additional, Platz, Elizabeth A., additional, Rennert, Gad, additional, Ruiz-Narvaez, Edward, additional, Sakoda, Lori C., additional, Scacheri, Peter C., additional, Schmit, Stephanie L., additional, Schoen, Robert E., additional, Stern, Mariana C., additional, Su, Yu-Ru, additional, Thomas, Duncan C., additional, Tian, Yu, additional, Tsilidis, Konstantinos K., additional, Ulrich, Cornelia M., additional, Um, Caroline Y., additional, van Duijnhoven, Fränzel J.B., additional, Van Guelpen, Bethany, additional, White, Emily, additional, Hsu, Li, additional, Moreno, Victor, additional, Peters, Ulrike, additional, Chan, Andrew T., additional, and Gauderman, W. James, additional

Published
2024
Full Text
View/download PDF

46. Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Author

Berndt, Sonja I., Vijai, Joseph, Benavente, Yolanda, Camp, Nicola J., Nieters, Alexandra, Wang, Zhaoming, Smedby, Karin E., Kleinstern, Geffen, Hjalgrim, Henrik, Besson, Caroline, Skibola, Christine F., Morton, Lindsay M., Brooks-Wilson, Angela R., Teras, Lauren R., Breeze, Charles, Arias, Joshua, Adami, Hans-Olov, Albanes, Demetrius, Anderson, Kenneth C., Ansell, Stephen M., Bassig, Bryan, Becker, Nikolaus, Bhatti, Parveen, Birmann, Brenda M., Boffetta, Paolo, Bracci, Paige M., Brennan, Paul, Brown, Elizabeth E., Burdett, Laurie, Cannon-Albright, Lisa A., Chang, Ellen T., Chiu, Brian C. H., Chung, Charles C., Clavel, Jacqueline, Cocco, Pierluigi, Colditz, Graham, Conde, Lucia, Conti, David V., Cox, David G., Curtin, Karen, Casabonne, Delphine, De Vivo, Immaculata, Diepstra, Arjan, Diver, W. Ryan, Dogan, Ahmet, Edlund, Christopher K., Foretova, Lenka, Fraumeni, Jr, Joseph F., Gabbas, Attilio, Ghesquières, Hervé, Giles, Graham G., Glaser, Sally, Glenn, Martha, Glimelius, Bengt, Gu, Jian, Habermann, Thomas M., Haiman, Christopher A., Haioun, Corinne, Hofmann, Jonathan N., Holford, Theodore R., Holly, Elizabeth A., Hutchinson, Amy, Izhar, Aalin, Jackson, Rebecca D., Jarrett, Ruth F., Kaaks, Rudolph, Kane, Eleanor, Kolonel, Laurence N., Kong, Yinfei, Kraft, Peter, Kricker, Anne, Lake, Annette, Lan, Qing, Lawrence, Charles, Li, Dalin, Liebow, Mark, Link, Brian K., Magnani, Corrado, Maynadie, Marc, McKay, James, Melbye, Mads, Miligi, Lucia, Milne, Roger L., Molina, Thierry J., Monnereau, Alain, Montalvan, Rebecca, North, Kari E., Novak, Anne J., Onel, Kenan, Purdue, Mark P., Rand, Kristin A., Riboli, Elio, Riby, Jacques, Roman, Eve, Salles, Gilles, Sborov, Douglas W., Severson, Richard K., Shanafelt, Tait D., Smith, Martyn T., Smith, Alexandra, Song, Kevin W., Song, Lei, Southey, Melissa C., Spinelli, John J., Staines, Anthony, Stephens, Deborah, Sutherland, Heather J., Tkachuk, Kaitlyn, Thompson, Carrie A., Tilly, Hervé, Tinker, Lesley F., Travis, Ruth C., Turner, Jenny, Vachon, Celine M., Vajdic, Claire M., Van Den Berg, Anke, Van Den Berg, David J., Vermeulen, Roel C. H., Vineis, Paolo, Wang, Sophia S., Weiderpass, Elisabete, Weiner, George J., Weinstein, Stephanie, Doo, Nicole Wong, Ye, Yuanqing, Yeager, Meredith, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zhang, Yawei, Zheng, Tongzhang, Ziv, Elad, Sampson, Joshua, Chatterjee, Nilanjan, Offit, Kenneth, Cozen, Wendy, Wu, Xifeng, Cerhan, James R., Chanock, Stephen J., Slager, Susan L., and Rothman, Nathaniel

Published
2023
Full Text
View/download PDF

47. Genetic overlap between autoimmune diseases and non‐Hodgkin lymphoma subtypes

Author

Din, Lennox, Sheikh, Mohammad, Kosaraju, Nikitha, Smedby, Karin Ekstrom, Bernatsky, Sasha, Berndt, Sonja I, Skibola, Christine F, Nieters, Alexandra, Wang, Sophia, McKay, James D, Cocco, Pierluigi, Maynadié, Marc, Foretová, Lenka, Staines, Anthony, Mack, Thomas M, de Sanjosé, Silvia, Vyse, Timothy J, Padyukov, Leonid, Monnereau, Alain, Arslan, Alan A, Moore, Amy, Brooks‐Wilson, Angela R, Novak, Anne J, Glimelius, Bengt, Birmann, Brenda M, Link, Brian K, Stewart, Carolyn, Vajdic, Claire M, Haioun, Corinne, Magnani, Corrado, Conti, David V, Cox, David G, Casabonne, Delphine, Albanes, Demetrius, Kane, Eleanor, Roman, Eve, Muzi, Giacomo, Salles, Gilles, Giles, Graham G, Adami, Hans‐Olov, Ghesquières, Hervé, De Vivo, Immaculata, Clavel, Jacqueline, Cerhan, James R, Spinelli, John J, Hofmann, Jonathan, Vijai, Joseph, Curtin, Karen, Costenbader, Karen H, Onel, Kenan, Offit, Kenneth, Teras, Lauren R, Morton, Lindsay, Conde, Lucia, Miligi, Lucia, Melbye, Mads, Ennas, Maria Grazia, Liebow, Mark, Purdue, Mark P, Glenn, Martha, Southey, Melissa C, Din, Morris, Rothman, Nathaniel, Camp, Nicola J, Doo, Nicole Wong, Becker, Nikolaus, Pradhan, Nisha, Bracci, Paige M, Boffetta, Paolo, Vineis, Paolo, Brennan, Paul, Kraft, Peter, Lan, Qing, Severson, Richard K, Vermeulen, Roel CH, Milne, Roger L, Kaaks, Rudolph, Travis, Ruth C, Weinstein, Stephanie J, Chanock, Stephen J, Ansell, Stephen M, Slager, Susan L, Zheng, Tongzhang, Zhang, Yawei, Benavente, Yolanda, Taub, Zachary, Madireddy, Lohith, Gourraud, Pierre‐Antoine, Oksenberg, Jorge R, Cozen, Wendy, Hjalgrim, Henrik, and Khankhanian, Pouya

Subjects
Biological Sciences, Genetics, Lymphoma, Arthritis, Neurodegenerative, Brain Disorders, Autoimmune Disease, Cancer, Human Genome, Rare Diseases, Hematology, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Alleles, Autoimmune Diseases, Female, Genetic Predisposition to Disease, HLA Antigens, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, autoimmune disease, genome-wide association study, meta-analysis, non-Hodgkin lymphoma, Public Health and Health Services, Epidemiology
Abstract

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Published
2019

48. Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

Author

Jiang, Xia, Finucane, Hilary K, Schumacher, Fredrick R, Schmit, Stephanie L, Tyrer, Jonathan P, Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B, Dennis, Joe, Conti, David V, Casey, Graham, Gaudet, Mia M, Huyghe, Jeroen R, Albanes, Demetrius, Aldrich, Melinda C, Andrew, Angeline S, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Antonenkova, Natalia N, Arnold, Susanne M, Aronson, Kristan J, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Batra, Jyotsna, Beckmann, Matthias W, Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I, Bickeböller, Heike, Bien, Stephanie A, Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brenton, James D, Brook, Mark N, Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D, Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Campbell, Peter T, Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Christiani, David C, Claes, Kathleen BM, Claessens, Frank, Clements, Judith, Collée, J Margriet, Correa, Marcia Cruz, Couch, Fergus J, Cox, Angela, Cunningham, Julie M, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L, Dörk, Thilo, Duell, Eric J, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Edlund, Christopher K, Edwards, Digna R Velez, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Ferris, Robert L, Liloglou, Triantafillos, Figueiredo, Jane C, Fletcher, Olivia, Fortner, Renée T, Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J, and Ganz, Patricia A

Subjects
MD Multidisciplinary
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

49. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author

Schmit, Stephanie L, Edlund, Christopher K, Schumacher, Fredrick R, Gong, Jian, Harrison, Tabitha A, Huyghe, Jeroen R, Qu, Chenxu, Melas, Marilena, Van Den Berg, David J, Wang, Hansong, Tring, Stephanie, Plummer, Sarah J, Albanes, Demetrius, Alonso, M Henar, Amos, Christopher I, Anton, Kristen, Aragaki, Aaron K, Arndt, Volker, Barry, Elizabeth L, Berndt, Sonja I, Bezieau, Stéphane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Carlson, Christopher S, Castelao, Jose E, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M, Church, Timothy, Coetzee, Gerhard A, Cotterchio, Michelle, Correa, Marcia Cruz, Curtis, Keith R, Duggan, David, Easton, Douglas F, English, Dallas, Feskens, Edith JM, Fischer, Rocky, FitzGerald, Liesel M, Fortini, Barbara K, Fritsche, Lars G, Fuchs, Charles S, Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Giovannucci, Edward L, Gogarten, Stephanie M, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M, Grady, William M, Greenson, Joel K, Gsur, Andrea, Gunter, Marc, Haiman, Christopher A, Hampe, Jochen, Harlid, Sophia, Harju, John F, Hayes, Richard B, Hofer, Philipp, Hoffmeister, Michael, Hopper, John L, Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J, Hunter, David J, Idos, Gregory E, Iwasaki, Motoki, Jackson, Rebecca D, Jacobs, Eric J, Jee, Sun Ha, Jenkins, Mark A, Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D, Kolonel, Laurence N, Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Küry, Sébastien, LaCroix, Andrea, Laurie, Cecelia A, Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, and Levine, David

Subjects
Prevention, Cancer, Digestive Diseases, Human Genome, Genetics, Clinical Research, Colo-Rectal Cancer, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Colorectal Neoplasms, Ethnicity, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Prognosis, United States, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrevious genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.MethodsWe conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.ResultsThe discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.ConclusionsThis study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Published
2019

50. Shared heritability and functional enrichment across six solid cancers.

Author

Jiang, Xia, Finucane, Hilary K, Schumacher, Fredrick R, Schmit, Stephanie L, Tyrer, Jonathan P, Han, Younghun, Michailidou, Kyriaki, Lesseur, Corina, Kuchenbaecker, Karoline B, Dennis, Joe, Conti, David V, Casey, Graham, Gaudet, Mia M, Huyghe, Jeroen R, Albanes, Demetrius, Aldrich, Melinda C, Andrew, Angeline S, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Antonenkova, Natalia N, Arnold, Susanne M, Aronson, Kristan J, Arun, Banu K, Bandera, Elisa V, Barkardottir, Rosa B, Barnes, Daniel R, Batra, Jyotsna, Beckmann, Matthias W, Benitez, Javier, Benlloch, Sara, Berchuck, Andrew, Berndt, Sonja I, Bickeböller, Heike, Bien, Stephanie A, Blomqvist, Carl, Boccia, Stefania, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brenton, James D, Brook, Mark N, Brunet, Joan, Brunnström, Hans, Buchanan, Daniel D, Burwinkel, Barbara, Butzow, Ralf, Cadoni, Gabriella, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Campbell, Peter T, Cancel-Tassin, Géraldine, Cannon-Albright, Lisa, Campa, Daniele, Caporaso, Neil, Carvalho, André L, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Chu, Christiani, David C, Claes, Kathleen BM, Claessens, Frank, Clements, Judith, Collée, J Margriet, Correa, Marcia Cruz, Couch, Fergus J, Cox, Angela, Cunningham, Julie M, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, deFazio, Anna, Devilee, Peter, Diez, Orland, Gago-Dominguez, Manuela, Donovan, Jenny L, Dörk, Thilo, Duell, Eric J, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Edlund, Christopher K, Edwards, Digna R Velez, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Ferris, Robert L, Liloglou, Triantafillos, Figueiredo, Jane C, Fletcher, Olivia, Fortner, Renée T, Fostira, Florentia, Franceschi, Silvia, Friedman, Eitan, Gallinger, Steven J, and Ganz, Patricia A

Subjects
Humans, Breast Neoplasms, Colorectal Neoplasms, Ovarian Neoplasms, Head and Neck Neoplasms, Lung Neoplasms, Prostatic Neoplasms, Genetic Predisposition to Disease, Neoplasm Proteins, Case-Control Studies, Smoking, Mental Disorders, Inheritance Patterns, Phenotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Prevention, Cancer, Breast Cancer, Genetics, Rare Diseases, Lung Cancer, Human Genome, Colo-Rectal Cancer, Digestive Diseases, Lung, MD Multidisciplinary
Abstract

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Published
2019

Catalog

Books, media, physical & digital resources
See catalog results