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210. Dispositional optimism and optimistic bias: Associations with cessation motivation, confidence, and attitudes.

Author

Everson, Nicole Senft, Klein, William M. P., Lee, Scott S., Selove, Rebecca, Sanderson, Maureen, Blot, William J., Tyndale, Rachel F., King, Stephen, Gilliam, Karen, Kundu, Suman, Steinwandel, Mark, Sternlieb, Sarah J., Andersen, Shaneda Warren, Friedman, Debra L., Connors, Erin, Fadden, Mary Kay, Freiberg, Matthew S., Wells, Quinn S., Canedo, Juan, and Young, Robert P.

Abstract

Objective: To test whether 2 conceptually overlapping constructs, dispositional optimism (generalized positive expectations) and optimistic bias (inaccurately low risk perceptions), may have different implications for smoking treatment engagement. Method: Predominantly Black, low-income Southern Community Cohort study smokers (n = 880) self-reported dispositional optimism and pessimism (Life Orientation Test "Revised subscales: 0 = neutral, 12 = high optimism/pessimism), comparative lung cancer risk (Low/Average/High), and information to calculate objective lung cancer risk (Low/Med/High). Perceived risk was categorized as accurate (perceived = objective), optimistically-biased (perceived< objective), or pessimistically-biased (perceived >objective). One-way ANOVAs tested associations between dispositional optimism/pessimism and perceived risk accuracy. Multivariable logistic regressions tested independent associations of optimism/pessimism and perceived risk accuracy with cessation motivation (Low/High), confidence (Low/High), and precision treatment attitudes (Favorable/Unfavorable), controlling for sociodemographics and nicotine dependence. Results: Mean dispositional optimism/pessimism scores were 8.41 (SD = 2.59) and 5.65 (SD = 3.02), respectively. Perceived lung cancer risk was 38% accurate, 27% optimistically-biased, and 35% pessimistically-biased. Accuracy was unrelated to dispositional optimism (F(2, 641) = 1.23, p = .29), though optimistically-biased (vs. pessimistically-biased) smokers had higher dispositional pessimism (F(2, 628) = 3.17, p = .043). Dispositional optimism was associated with higher confidence (Adjusted odds ratio [AOR] = 1.71, 95% CI [1.42, 2.06], p < .001) and favorable precision treatment attitudes (AOR = 1.66, 95% CI [1.37, 2.01], p < .001). Optimistically-biased (vs. accurate) risk perception was associated with lower motivation (AOR = .64, 95% CI [.42, .98], p = .041) and less favorable precision treatment attitudes (AOR = .59, 95% CI [.38, .94], p = .029). Conclusions: Dispositional optimism and lung cancer risk perception accuracy were unrelated. Dispositional optimism was associated with favorable engagement-related outcomes and optimistically-biased risk perception with unfavorable outcomes, reinforcing the distinctiveness of these constructs and their implications for smoking treatment. [ABSTRACT FROM AUTHOR]

Published
2022
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213. Gestational diabetes and risk of breast cancer before age 55 years

Author

Bertrand, Kimberly A, primary, O’Brien, Katie M, additional, Wright, Lauren B, additional, Palmer, Julie R, additional, Blot, William J, additional, Eliassen, A Heather, additional, Rosenberg, Lynn, additional, Sandin, Sven, additional, Tobias, Deirdre, additional, Weiderpass, Elisabete, additional, Zheng, Wei, additional, Swerdlow, Anthony J, additional, Schoemaker, Minouk J, additional, Nichols, Hazel B, additional, and Sandler, Dale P, additional

Published
2021
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220. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, and Lu, Yong-Jie

Subjects
Male, Urologic Diseases, Aging, Quantitative Trait Loci, Medical and Health Sciences, Risk Factors, Clinical Research, Odds Ratio, Genetics, Humans, 2.1 Biological and endogenous factors, Neoplasm Invasiveness, Genetic Predisposition to Disease, Aetiology, Cancer, Prevention, Prostate Cancer, Racial Groups, Human Genome, Prostatic Neoplasms, Molecular Sequence Annotation, Genomics, Middle Aged, Biological Sciences, Phenotype, Good Health and Well Being, Genetic Loci, Software, Genome-Wide Association Study, Statistical Distributions, Developmental Biology
Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Published
2021

221. 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 M.L., 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., other, and, 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 M.L., 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., and other, and

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 < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Published
2021

222. Publisher Correction : Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Author

Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo L J, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, West, Catharine M L, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M, Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Teixeira, Manuel R, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T, Fontham, Elizabeth T H, Mohler, James, Taylor, Jack A, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C, Huff, Chad D, Strom, Sara S, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J, Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A, Hsing, Ann W, Kittles, Rick A, Murphy, Adam B, Logothetis, Christopher J, Kim, Jeri, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm J M, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F, Lin, Daniel W, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J, Jenster, Guido, van Schaik, Ron H N, Hu, Jennifer J, Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I, Van Den Eeden, Stephen K, Easton, Douglas F, Chanock, Stephen J, Cook, Michael B, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Eeles, Rosalind A, Kote-Jarai, Zsofia, Haiman, Christopher A, Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo L J, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, West, Catharine M L, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M, Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Teixeira, Manuel R, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T, Fontham, Elizabeth T H, Mohler, James, Taylor, Jack A, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C, Huff, Chad D, Strom, Sara S, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J, Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A, Hsing, Ann W, Kittles, Rick A, Murphy, Adam B, Logothetis, Christopher J, Kim, Jeri, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm J M, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F, Lin, Daniel W, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J, Jenster, Guido, van Schaik, Ron H N, Hu, Jennifer J, Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I, Van Den Eeden, Stephen K, Easton, Douglas F, Chanock, Stephen J, Cook, Michael B, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Eeles, Rosalind A, Kote-Jarai, Zsofia, and Haiman, Christopher A

Published
2021
Full Text
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223. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Author

Huynh-Le, Minh-Phuong, 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, PRACTICAL Consortium, Huynh-Le, Minh-Phuong, 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

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 < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Published
2021

224. African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer.

Author

Karunamuni, Roshan A, Karunamuni, Roshan A, Huynh-Le, Minh-Phuong, Fan, Chun C, Thompson, Wesley, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, UKGPCS Collaborators, Lophatananon, Artitaya, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Blot, William J, Zheng, Wei, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Park, Jong Y, Lin, Hui-Yi, Bensen, Jeannette T, Fontham, Elizabeth TH, Mohler, James L, Taylor, Jack A, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Romana, Marc, Leach, Robin J, John, Esther M, Fowke, Jay, Bush, William S, Aldrich, Melinda, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Parent, Marie-Élise, Hu, Jennifer J, Sanderson, Maureen, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, PRACTICAL Consortium, Karunamuni, Roshan A, Karunamuni, Roshan A, Huynh-Le, Minh-Phuong, Fan, Chun C, Thompson, Wesley, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, UKGPCS Collaborators, Lophatananon, Artitaya, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Blot, William J, Zheng, Wei, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Park, Jong Y, Lin, Hui-Yi, Bensen, Jeannette T, Fontham, Elizabeth TH, Mohler, James L, Taylor, Jack A, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Romana, Marc, Leach, Robin J, John, Esther M, Fowke, Jay, Bush, William S, Aldrich, Melinda, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Parent, Marie-Élise, Hu, Jennifer J, Sanderson, Maureen, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M, and PRACTICAL Consortium

Abstract

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

Published
2021

225. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David, V, Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Al Olama, Ali Amin, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Roder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Elise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E. Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sorensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gomez-Caamano, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandao, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T. H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja, I, Van den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, Haiman, Christopher A., Conti, David, V, Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Al Olama, Ali Amin, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Roder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Jr., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie-Elise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E. Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sorensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M. L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, Menegaux, Florence, Truong, Therese, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gomez-Caamano, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandao, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T. H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castano-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J. M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja, I, Van den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, and Haiman, Christopher A.

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Published
2021
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226. Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults

Author

Zahed, Hana, Johansson, Mattias, Ueland, Per M., Midttun, Øivind, Milne, Roger L., Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Grankvist, Kjell, Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loic, Wilkens, Lynne R., Weinstein, Stephanie J., Albanes, Demetrius, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Muller, David, Brennan, Paul, Guida, Florence, Robbins, Hilary A., Zahed, Hana, Johansson, Mattias, Ueland, Per M., Midttun, Øivind, Milne, Roger L., Giles, Graham G., Manjer, Jonas, Sandsveden, Malte, Langhammer, Arnulf, Sørgjerd, Elin Pettersen, Grankvist, Kjell, Johansson, Mikael, Freedman, Neal D., Huang, Wen-Yi, Chen, Chu, Prentice, Ross, Stevens, Victoria L., Wang, Ying, Le Marchand, Loic, Wilkens, Lynne R., Weinstein, Stephanie J., Albanes, Demetrius, Cai, Qiuyin, Blot, William J., Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Shu, Xiao-Ou, Zheng, Wei, Yuan, Jian-Min, Koh, Woon-Puay, Visvanathan, Kala, Sesso, Howard D., Zhang, Xuehong, Gaziano, J. Michael, Fanidi, Anouar, Muller, David, Brennan, Paul, Guida, Florence, and Robbins, Hilary A.

Abstract

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.

Published
2021
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227. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Author

Graff, Mariaelisa, Graff, Mariaelisa, Justice, Anne E, Young, Kristin L, Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S, Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F, Wojczynski, Mary K, Yanek, Lisa R, Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A, Aldrich, Melinda C, Allison, Matthew A, Ambrosone, Christine B, Ambs, Stefan, Amos, Christopher, Arnett, Donna K, Atwood, Larry, Bandera, Elisa V, Bartz, Traci, Becker, Diane M, Berndt, Sonja I, Bernstein, Leslie, Bielak, Lawrence F, Blot, William J, Bottinger, Erwin P, Bowden, Donald W, Bradfield, Jonathan P, Brody, Jennifer A, Broeckel, Ulrich, Burke, Gregory, Cade, Brian E, Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J, Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I, Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston WK, Chu, Lisa, Coetzee, Gerry A, Conti, David V, Cooper, Richard S, Cushman, Mary, Demerath, Ellen, Deming, Sandra L, Dimitrov, Latchezar, Ding, Jingzhong, Diver, W Ryan, Duan, Qing, Evans, Michele K, Falusi, Adeyinka G, Faul, Jessica D, Fornage, Myriam, Fox, Caroline, Freedman, Barry I, Garcia, Melissa, Gillanders, Elizabeth M, Goodman, Phyllis, Gottesman, Omri, Grant, Struan FA, Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B, Harris, Curtis C, Henderson, Brian E, Hennis, Anselm, Hernandez, Dena G, Hirschhorn, Joel N, McNeill, Lorna Haughton, Howard, Timothy D, Howard, Barbara, Hsing, Ann W, Hsu, Yu-Han H, Hu, Jennifer J, Huff, Chad D, Huo, Dezheng, Ingles, Sue A, Irvin, Marguerite R, John, Esther M, Johnson, Karen C, Jordan, Joanne M, Kabagambe, Edmond K, Kang, Sun J, Kardia, Sharon L, Keating, Brendan J, Kittles, Rick A, Klein, Eric A, Kolb, Suzanne, Kolonel, Laurence N, Graff, Mariaelisa, Graff, Mariaelisa, Justice, Anne E, Young, Kristin L, Marouli, Eirini, Zhang, Xinruo, Fine, Rebecca S, Lim, Elise, Buchanan, Victoria, Rand, Kristin, Feitosa, Mary F, Wojczynski, Mary K, Yanek, Lisa R, Shao, Yaming, Rohde, Rebecca, Adeyemo, Adebowale A, Aldrich, Melinda C, Allison, Matthew A, Ambrosone, Christine B, Ambs, Stefan, Amos, Christopher, Arnett, Donna K, Atwood, Larry, Bandera, Elisa V, Bartz, Traci, Becker, Diane M, Berndt, Sonja I, Bernstein, Leslie, Bielak, Lawrence F, Blot, William J, Bottinger, Erwin P, Bowden, Donald W, Bradfield, Jonathan P, Brody, Jennifer A, Broeckel, Ulrich, Burke, Gregory, Cade, Brian E, Cai, Qiuyin, Caporaso, Neil, Carlson, Chris, Carpten, John, Casey, Graham, Chanock, Stephen J, Chen, Guanjie, Chen, Minhui, Chen, Yii-Der I, Chen, Wei-Min, Chesi, Alessandra, Chiang, Charleston WK, Chu, Lisa, Coetzee, Gerry A, Conti, David V, Cooper, Richard S, Cushman, Mary, Demerath, Ellen, Deming, Sandra L, Dimitrov, Latchezar, Ding, Jingzhong, Diver, W Ryan, Duan, Qing, Evans, Michele K, Falusi, Adeyinka G, Faul, Jessica D, Fornage, Myriam, Fox, Caroline, Freedman, Barry I, Garcia, Melissa, Gillanders, Elizabeth M, Goodman, Phyllis, Gottesman, Omri, Grant, Struan FA, Guo, Xiuqing, Hakonarson, Hakon, Haritunians, Talin, Harris, Tamara B, Harris, Curtis C, Henderson, Brian E, Hennis, Anselm, Hernandez, Dena G, Hirschhorn, Joel N, McNeill, Lorna Haughton, Howard, Timothy D, Howard, Barbara, Hsing, Ann W, Hsu, Yu-Han H, Hu, Jennifer J, Huff, Chad D, Huo, Dezheng, Ingles, Sue A, Irvin, Marguerite R, John, Esther M, Johnson, Karen C, Jordan, Joanne M, Kabagambe, Edmond K, Kang, Sun J, Kardia, Sharon L, Keating, Brendan J, Kittles, Rick A, Klein, Eric A, Kolb, Suzanne, and Kolonel, Laurence N

Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Published
2021

228. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David V., Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L.J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie Élise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E.Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong Jie, Zhang, Hong Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M.L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T.H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J.M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H.N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I., Van Den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, Haiman, Christopher A., Conti, David V., Darst, Burcu F., Moss, Lilit C., Saunders, Edward J., Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R., Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Sahimi, Ali, Hoffmann, Thomas J., Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R., Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Schleutker, Johanna, Tammela, Teuvo L.J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A., Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M., Ghoussaini, Maya, Travis, Ruth C., Key, Tim J., Riboli, Elio, Park, Jong Y., Sellers, Thomas A., Lin, Hui Yi, Albanes, Demetrius, Weinstein, Stephanie J., Mucci, Lorelei A., Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J., Penney, Kathryn L., Turman, Constance, Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Parent, Marie Élise, Stanford, Janet L., Ostrander, Elaine A., Geybels, Milan S., Koutros, Stella, Freeman, Laura E.Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L., Hoover, Robert N., Machiela, Mitchell J., Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J., Zheng, Wei, Yeboah, Edward D., Mensah, James E., Lu, Yong Jie, Zhang, Hong Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan Chao, Sun, Zan, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., West, Catharine M.L., Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M., Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay Tee, Ingles, Sue A., Stern, Mariana C., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Teixeira, Manuel R., Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T., Fontham, Elizabeth T.H., Mohler, James, Taylor, Jack A., Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai Uwe, Klein, Eric A., Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Kim, Jeri, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J.M., Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo Hwang, Newcomb, Lisa F., Lin, Daniel W., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Bush, William S., Aldrich, Melinda C., Crawford, Dana C., Srivastava, Shiv, Cullen, Jennifer C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H.N., Hu, Jennifer J., Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I., Van Den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, and Haiman, Christopher A.

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Published
2021

234. Genome-wide association study (GWAS) of circulating vitamin D outcomes among individuals of African ancestry

Author

Parlato, Lisa A., Welch, Rene, Ong, Irene M., Long, Jirong, Cai, Qiuyin, Steinwandel, Mark D., Blot, William J., Zheng, Wei, and Warren Andersen, Shaneda

Abstract

Vitamin D deficiency is more common among African-ancestry individuals and may be associated with adverse health outcomes. Vitamin D binding protein (VDBP) regulates concentrations of biologically active vitamin D.

Published
2023
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236. A Pooled Case-only Analysis of Reproductive Risk Factors and Breast Cancer Subtype Among Black Women in the Southeastern United States

Author

Sanderson, Maureen, primary, Pal, Tuya, additional, Beeghly-Fadiel, Alicia, additional, Fadden, Mary Kay, additional, Dujon, Steffie-Ann, additional, Clinton, Chrystina, additional, Jimenez, Cecilia, additional, Davis, Jennifer, additional, Fortune, Mieke, additional, Thompson, Jasmine, additional, Benson, Kiera, additional, Conley, Nicholas, additional, Reid, Sonya, additional, Tezak, Ann, additional, Shu, Xiao-Ou, additional, Zheng, Wei, additional, Blot, William J., additional, and Lipworth, Loren, additional

Published
2021
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237. Smoking Quit Rates Among Menthol vs Nonmenthol Smokers: Implications Regarding a US Ban on the Sale of Menthol Cigarettes.

Author

Munro, Heather M, Shrubsole, Martha J, Zheng, Wei, Wen, Wanqing, and Blot, William J

Subjects
RESEARCH, SMOKING cessation, META-analysis, EVALUATION research, COMPARATIVE studies, RESEARCH funding, TOBACCO products, SMOKING, ALCOHOLS (Chemical class), LONGITUDINAL method
Abstract

Background: A ban on the sale of menthol cigarettes in the United States is currently under consideration. A justification is that menthol cigarettes are harder to quit, particularly for African American smokers who use menthols much more frequently than White smokers, but epidemiologic data are limited.Methods: In a cohort of 16 425 mostly low-income African American and White current cigarette smokers enrolled during 2002-2009, we computed smoking quit and reuptake rates at 3 follow-ups conducted means of 4.6, 7.7, and 11 years after entry. Generalized estimation equations were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for quitting and resuming smoking for menthol vs nonmenthol smokers adjusted for race, age, education, income, and smoking pack-years.Results: Crude annual quit rates among current smokers were 4.3% for menthol and 4.5% for nonmenthol smokers, with adjusted odds ratios of quitting for menthol vs nonmenthol smokers of 1.01 (95% CI = 0.91 to 1.11) overall, 0.99 (95% CI = 0.87 to 1.12) among African American smokers, and 1.02 (95% CI = 0.88 to 1.20) among White smokers. Crude annual smoking reuptake rates were somewhat higher among menthol smokers (8.4%) than nonmenthol smokers (7.1%), with an adjusted odds ratio of 1.19 (95% CI = 0.97 to 1.47), but net quit rates remained similar (OR = 1.01, 95% CI = 0.90 to 1.13 overall; OR = 1.00, 95% CI = 0.86 to 1.15 among African American participants; and OR = 1.04, 95% CI = 0.87 to 1.24 among White participants).Conclusions: This large-scale prospective survey revealed similar quit rates among menthol and nonmenthol smokers. Results contribute to policy discussions, especially if, as a meta-analysis suggests, lung cancer risk is higher for nonmenthol smokers and a ban leads menthol smokers to switch to nonmenthol cigarettes. [ABSTRACT FROM AUTHOR]

Published
2022
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238. Red meat consumption, cooking mutagens,NAT1 /2genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts

Author

Huang, Brian Z., primary, Wang, Songren, additional, Bogumil, David, additional, Wilkens, Lynne R., additional, Wu, Lang, additional, Blot, William J., additional, Zheng, Wei, additional, Shu, Xiao‐Ou, additional, Pandol, Stephen J., additional, Le Marchand, Loïc, additional, and Setiawan, Veronica Wendy, additional

Published
2021
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240. Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Author

Graff, Mariaelisa, primary, Justice, Anne E., additional, Young, Kristin L., additional, Marouli, Eirini, additional, Zhang, Xinruo, additional, Fine, Rebecca S., additional, Lim, Elise, additional, Buchanan, Victoria, additional, Rand, Kristin, additional, Feitosa, Mary F., additional, Wojczynski, Mary K., additional, Yanek, Lisa R., additional, Shao, Yaming, additional, Rohde, Rebecca, additional, Adeyemo, Adebowale A., additional, Aldrich, Melinda C., additional, Allison, Matthew A., additional, Ambrosone, Christine B., additional, Ambs, Stefan, additional, Amos, Christopher, additional, Arnett, Donna K., additional, Atwood, Larry, additional, Bandera, Elisa V., additional, Bartz, Traci, additional, Becker, Diane M., additional, Berndt, Sonja I., additional, Bernstein, Leslie, additional, Bielak, Lawrence F., additional, Blot, William J., additional, Bottinger, Erwin P., additional, Bowden, Donald W., additional, Bradfield, Jonathan P., additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Burke, Gregory, additional, Cade, Brian E., additional, Cai, Qiuyin, additional, Caporaso, Neil, additional, Carlson, Chris, additional, Carpten, John, additional, Casey, Graham, additional, Chanock, Stephen J., additional, Chen, Guanjie, additional, Chen, Minhui, additional, Chen, Yii-Der I., additional, Chen, Wei-Min, additional, Chesi, Alessandra, additional, Chiang, Charleston W.K., additional, Chu, Lisa, additional, Coetzee, Gerry A., additional, Conti, David V., additional, Cooper, Richard S., additional, Cushman, Mary, additional, Demerath, Ellen, additional, Deming, Sandra L., additional, Dimitrov, Latchezar, additional, Ding, Jingzhong, additional, Diver, W. Ryan, additional, Duan, Qing, additional, Evans, Michele K., additional, Falusi, Adeyinka G., additional, Faul, Jessica D., additional, Fornage, Myriam, additional, Fox, Caroline, additional, Freedman, Barry I., additional, Garcia, Melissa, additional, Gillanders, Elizabeth M., additional, Goodman, Phyllis, additional, Gottesman, Omri, additional, Grant, Struan F.A., additional, Guo, Xiuqing, additional, Hakonarson, Hakon, additional, Haritunians, Talin, additional, Harris, Tamara B., additional, Harris, Curtis C., additional, Henderson, Brian E., additional, Hennis, Anselm, additional, Hernandez, Dena G., additional, Hirschhorn, Joel N., additional, McNeill, Lorna Haughton, additional, Howard, Timothy D., additional, Howard, Barbara, additional, Hsing, Ann W., additional, Hsu, Yu-Han H., additional, Hu, Jennifer J., additional, Huff, Chad D., additional, Huo, Dezheng, additional, Ingles, Sue A., additional, Irvin, Marguerite R., additional, John, Esther M., additional, Johnson, Karen C., additional, Jordan, Joanne M., additional, Kabagambe, Edmond K., additional, Kang, Sun J., additional, Kardia, Sharon L., additional, Keating, Brendan J., additional, Kittles, Rick A., additional, Klein, Eric A., additional, Kolb, Suzanne, additional, Kolonel, Laurence N., additional, Kooperberg, Charles, additional, Kuller, Lewis, additional, Kutlar, Abdullah, additional, Lange, Leslie, additional, Langefeld, Carl D., additional, Le Marchand, Loic, additional, Leonard, Hampton, additional, Lettre, Guillaume, additional, Levin, Albert M., additional, Li, Yun, additional, Li, Jin, additional, Liu, Yongmei, additional, Liu, Youfang, additional, Liu, Simin, additional, Lohman, Kurt, additional, Lotay, Vaneet, additional, Lu, Yingchang, additional, Maixner, William, additional, Manson, JoAnn E., additional, McKnight, Barbara, additional, Meng, Yan, additional, Monda, Keri L., additional, Monroe, Kris, additional, Moore, Jason H., additional, Mosley, Thomas H., additional, Mudgal, Poorva, additional, Murphy, Adam B., additional, Nadukuru, Rajiv, additional, Nalls, Mike A., additional, Nathanson, Katherine L., additional, Nayak, Uma, additional, N’Diaye, Amidou, additional, Nemesure, Barbara, additional, Neslund-Dudas, Christine, additional, Neuhouser, Marian L., additional, Nyante, Sarah, additional, Ochs-Balcom, Heather, additional, Ogundiran, Temidayo O., additional, Ogunniyi, Adesola, additional, Ojengbede, Oladosu, additional, Okut, Hayrettin, additional, Olopade, Olufunmilayo I., additional, Olshan, Andrew, additional, Padhukasahasram, Badri, additional, Palmer, Julie, additional, Palmer, Cameron D., additional, Palmer, Nicholette D., additional, Papanicolaou, George, additional, Patel, Sanjay R., additional, Pettaway, Curtis A., additional, Peyser, Patricia A., additional, Press, Michael F., additional, Rao, D.C., additional, Rasmussen-Torvik, Laura J., additional, Redline, Susan, additional, Reiner, Alex P., additional, Rhie, Suhn K., additional, Rodriguez-Gil, Jorge L., additional, Rotimi, Charles N., additional, Rotter, Jerome I., additional, Ruiz-Narvaez, Edward A., additional, Rybicki, Benjamin A., additional, Salako, Babatunde, additional, Sale, Michele M., additional, Sanderson, Maureen, additional, Schadt, Eric, additional, Schreiner, Pamela J., additional, Schurmann, Claudia, additional, Schwartz, Ann G., additional, Shriner, Daniel A., additional, Signorello, Lisa B., additional, Singleton, Andrew B., additional, Siscovick, David S., additional, Smith, Jennifer A., additional, Smith, Shad, additional, Speliotes, Elizabeth, additional, Spitz, Margaret, additional, Stanford, Janet L., additional, Stevens, Victoria L., additional, Stram, Alex, additional, Strom, Sara S., additional, Sucheston, Lara, additional, Sun, Yan V., additional, Tajuddin, Salman M., additional, Taylor, Herman, additional, Taylor, Kira, additional, Tayo, Bamidele O., additional, Thun, Michael J., additional, Tucker, Margaret A., additional, Vaidya, Dhananjay, additional, Van Den Berg, David J., additional, Vedantam, Sailaja, additional, Vitolins, Mara, additional, Wang, Zhaoming, additional, Ware, Erin B., additional, Wassertheil-Smoller, Sylvia, additional, Weir, David R., additional, Wiencke, John K., additional, Williams, Scott M., additional, Williams, L. Keoki, additional, Wilson, James G., additional, Witte, John S., additional, Wrensch, Margaret, additional, Wu, Xifeng, additional, Yao, Jie, additional, Zakai, Neil, additional, Zanetti, Krista, additional, Zemel, Babette S., additional, Zhao, Wei, additional, Zhao, Jing Hua, additional, Zheng, Wei, additional, Zhi, Degui, additional, Zhou, Jie, additional, Zhu, Xiaofeng, additional, Ziegler, Regina G., additional, Zmuda, Joe, additional, Zonderman, Alan B., additional, Psaty, Bruce M., additional, Borecki, Ingrid B., additional, Cupples, L. Adrienne, additional, Liu, Ching-Ti, additional, Haiman, Christopher A., additional, Loos, Ruth, additional, Ng, Maggie C.Y., additional, and North, Kari E., additional

Published
2021
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241. Prediagnostic Antibody Responses to Fusobacterium nucleatum Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium

Author

Lo, Chun-Han, primary, Blot, William J., additional, Teras, Lauren R., additional, Visvanathan, Kala, additional, Le Marchand, Loïc, additional, Haiman, Christopher A., additional, Chen, Yu, additional, Sesso, Howard D., additional, Wassertheil-Smoller, Sylvia, additional, Tinker, Lesley F., additional, Peek, Richard M., additional, Potter, John D., additional, Cover, Timothy L., additional, Zeleniuch-Jacquotte, Anne, additional, Berndt, Sonja I., additional, Waterboer, Tim, additional, Epplein, Meira, additional, Butt, Julia, additional, and Song, Mingyang, additional

Published
2021
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244. Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans

Author

Wang, Hansong, Haiman, Christopher A., Burnett, Terrilea, Fortini, Barbara K., Kolonel, Laurence N., Henderson, Brian E., Signorello, Lisa B., Blot, William J., Keku, Temitope O., Berndt, Sonja I., Newcomb, Polly A., Pande, Mala, Amos, Christopher I., West, Dee W., Casey, Graham, Sandler, Robert S., Haile, Robert, Stram, Daniel O., and Le Marchand, Loïc

Published
2013
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245. An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

Author

Wu, Lang, Yang, Yaohua, Guo, Xingyi, Shu, Xiao-Ou, Cai, Qiuyin, Shu, Xiang, Li, Bingshan, Tao, Ran, Wu, Chong, Nikas, Jason B., Sun, Yanfa, Zhu, Jingjing, Brenner, Hermann, John, Esther M., Clements, Judith, Grindedal, Eli Marie, Stanford, Janet L., Kote-Jarai, Zsofia, Haiman, Christopher A., Zheng, Wei, Long, Jirong, Eeles, Rosalind A., Henderson, Brian E., Schumacher, Fredrick R., Easton, Douglas, Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan M., Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Cancel-Tassin, Géraldine, Koutros, Stella, Sorensen, Karina Dalsgaard, 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., Kibel, Adam S., Vega, Ana, Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Cybulski, Cezary, Nordestgaard, Børge G., Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Gamulin, Marija, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Dominguez, Manuela Gago, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Thibodeau, Stephen N., Hunter, David J., Blot, William J., Riboli, Elio, Li, Bingshan [0000-0003-2129-168X], Wu, Chong [0000-0002-8400-1785], Nikas, Jason B. [0000-0001-9703-0422], Roobol, Monique J. [0000-0001-6967-1708], Giles, Graham G. [0000-0003-4946-9099], Park, Jong Y. [0000-0002-6384-6447], Eeles, Rosalind A. [0000-0002-3698-6241], Zheng, Wei [0000-0003-1226-070X], and Apollo - University of Cambridge Repository

Subjects
631/208, 631/67/68, article, 631/67/2324, urologic and male genital diseases
Abstract

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.

Published
2020
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246. Comparing diabetes prevalence between African Americans and Whites of similar socioeconomic status

Author

Signorello, Lisa B., Schlundt, David G., Cohen, Sarah S., Steinwandel, Mark D., Buchowski, Maciej S., McLaughlin, Joseph K., Hargreaves, Margaret K., and Blot, William J.

Subjects
Social classes -- Health aspects, Diabetes -- Risk factors, Diabetes -- Research, Diabetes -- Demographic aspects, Government, Health care industry
Abstract

Objectives. We investigated whether racial disparities in the prevalence of type 2 diabetes exist beyond what may be attributable to differences in socioeconomic status (SES) and other modifiable risk factors. Methods. We analyzed data from 34331 African American and 9491 White adults aged 40 to 79 years recruited into the ongoing Southern Community Cohort Study. Participants were enrolled at community health centers and had similar socioeconomic circumstances and risk factor profiles. We used logistic regression to estimate the association between race and prevalence of self-reported diabetes after taking into account age, SES, health insurance coverage, body mass index, physical activity, and hypertension. Results. Multivariate analyses accounting for several diabetes risk factors did not provide strong support for higher diabetes prevalence rates among African Americans than among Whites (men: odds ratio [OR] = 1.07; 95% confidence interval [CI] = 0.95, 1.20); women: OR = 1.13, 95% CI = 1.04, 1.22). Conclusions. Our findings suggest that major differences in diabetes prevalence between African Americans and Whites may simply reflect differences in established risk factors for the disease, such as SES, that typically vary according to race.

Published
2007

247. Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Author

Huang, Joyce Y., Larose, Tricia L., Luu, Hung N., Wang, Renwei, Fanidi, Anouar, Alcala, Karine, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Caporaso, Neil E., Purdue, Mark P., Ziegler, Regina G., Freedman, Neal D., Lan, Qing, Prentice, Ross L., Pettinger, Mary, Thomson, Cynthia A., Cai, Qiuyin, Wu, Jie, Blot, William J., Shu, Xiao-Ou, Zheng, Wei, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loic, Wilkens, Lynn R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Hveem, Kristian, Xiang, Yong-Bing, Li, Hong-Lan, Gao, Yu-Tang, Visvanathan, Kala, Ueland, Per M., Midttun, Oivind, Ulvi, Arve, Buring, Julie E., Lee, I-Min, SeSS, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline, Koh, Woon-Puay, Brennan, Paul, Johansson, Mattias, Yuan, Jian-Min, Han, Jiali, Huang, Joyce Y., Larose, Tricia L., Luu, Hung N., Wang, Renwei, Fanidi, Anouar, Alcala, Karine, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Caporaso, Neil E., Purdue, Mark P., Ziegler, Regina G., Freedman, Neal D., Lan, Qing, Prentice, Ross L., Pettinger, Mary, Thomson, Cynthia A., Cai, Qiuyin, Wu, Jie, Blot, William J., Shu, Xiao-Ou, Zheng, Wei, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loic, Wilkens, Lynn R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Hveem, Kristian, Xiang, Yong-Bing, Li, Hong-Lan, Gao, Yu-Tang, Visvanathan, Kala, Ueland, Per M., Midttun, Oivind, Ulvi, Arve, Buring, Julie E., Lee, I-Min, SeSS, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline, Koh, Woon-Puay, Brennan, Paul, Johansson, Mattias, Yuan, Jian-Min, and Han, Jiali

Abstract

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression., Grant numbers United States Department of Health & Human Services, National Institutes of Health (NIH) - USA, and NIH National Cancer Institute (NCI): P01CA87969, P30CA016087, R01CA092447, R01CA144034, U01CA155340, U01CA202979, UM1CA167552, UM1CA173640, UM1CA182876, UM1CA182910, UM1CA182934, UM1CA186107Grant numbers United States Department of Health & Human Services and National Institutes of Health (NIH) - USACA047988, CA097193, CA182913, CA34944, CA40360, HL043851, HL080467, HL099355, HL26490, HL34595, P30ES000260

Published
2020
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248. A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Author

Du, Zhaohui, Du, Zhaohui, Weinhold, Niels, Song, Gregory Chi, Rand, Kristin A, Van Den Berg, David J, Hwang, Amie E, Sheng, Xin, Hom, Victor, Ailawadhi, Sikander, Nooka, Ajay K, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn, Mohrbacher, Ann, Stram, Alexander, Berndt, Sonja I, Blot, William J, Casey, Graham, Stevens, Victoria L, Kittles, Rick, Goodman, Phyllis J, Diver, W Ryan, Hennis, Anselm, Nemesure, Barbara, Klein, Eric A, Rybicki, Benjamin A, Stanford, Janet L, Witte, John S, Signorello, Lisa, John, Esther M, Bernstein, Leslie, Stroup, Antoinette M, Stephens, Owen W, Zangari, Maurizio, Van Rhee, Frits, Olshan, Andrew, Zheng, Wei, Hu, Jennifer J, Ziegler, Regina, Nyante, Sarah J, Ingles, Sue Ann, Press, Michael F, Carpten, John David, Chanock, Stephen J, Mehta, Jayesh, Colditz, Graham A, Wolf, Jeffrey, Martin, Thomas G, Tomasson, Michael, Fiala, Mark A, Terebelo, Howard, Janakiraman, Nalini, Kolonel, Laurence, Anderson, Kenneth C, Le Marchand, Loic, Auclair, Daniel, Chiu, Brian C-H, Ziv, Elad, Stram, Daniel, Vij, Ravi, Bernal-Mizrachi, Leon, Morgan, Gareth J, Zonder, Jeffrey A, Huff, Carol Ann, Lonial, Sagar, Orlowski, Robert Z, Conti, David V, Haiman, Christopher A, Cozen, Wendy, Du, Zhaohui, Du, Zhaohui, Weinhold, Niels, Song, Gregory Chi, Rand, Kristin A, Van Den Berg, David J, Hwang, Amie E, Sheng, Xin, Hom, Victor, Ailawadhi, Sikander, Nooka, Ajay K, Singhal, Seema, Pawlish, Karen, Peters, Edward S, Bock, Cathryn, Mohrbacher, Ann, Stram, Alexander, Berndt, Sonja I, Blot, William J, Casey, Graham, Stevens, Victoria L, Kittles, Rick, Goodman, Phyllis J, Diver, W Ryan, Hennis, Anselm, Nemesure, Barbara, Klein, Eric A, Rybicki, Benjamin A, Stanford, Janet L, Witte, John S, Signorello, Lisa, John, Esther M, Bernstein, Leslie, Stroup, Antoinette M, Stephens, Owen W, Zangari, Maurizio, Van Rhee, Frits, Olshan, Andrew, Zheng, Wei, Hu, Jennifer J, Ziegler, Regina, Nyante, Sarah J, Ingles, Sue Ann, Press, Michael F, Carpten, John David, Chanock, Stephen J, Mehta, Jayesh, Colditz, Graham A, Wolf, Jeffrey, Martin, Thomas G, Tomasson, Michael, Fiala, Mark A, Terebelo, Howard, Janakiraman, Nalini, Kolonel, Laurence, Anderson, Kenneth C, Le Marchand, Loic, Auclair, Daniel, Chiu, Brian C-H, Ziv, Elad, Stram, Daniel, Vij, Ravi, Bernal-Mizrachi, Leon, Morgan, Gareth J, Zonder, Jeffrey A, Huff, Carol Ann, Lonial, Sagar, Orlowski, Robert Z, Conti, David V, Haiman, Christopher A, and Cozen, Wendy

Abstract

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Published
2020

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