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1. A novel donor-derived cell-free DNA assay for the detection of acute rejection in heart transplantation

Author

Kim, Paul J, Olymbios, Michael, Siu, Alfonso, Pinzon, Omar Wever, Adler, Eric, Liang, Nathan, Swenerton, Ryan, Sternberg, Jonathan, Kaur, Navchetan, Ahmed, Ebad, Chen, Yen-An, Fehringer, Gordon, Demko, Zachary P, Billings, Paul R, and Stehlik, Josef

Subjects
Organ Transplantation, Cardiovascular, Transplantation, Clinical Research, Adult, Biomarkers, Cell-Free Nucleic Acids, Graft Rejection, Heart Transplantation, Humans, Tissue Donors, acute rejection, heart transplant, cell free DNA, endomyocardial biopsy, acute cellular rejection, antibody mediated rejection, graft dysfunction, Cardiorespiratory Medicine and Haematology, Surgery
Abstract

BackgroundEndomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients.MethodsPlasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures.ResultsA total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pc < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction ≥0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples.ConclusionsThis novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients.

Published
2022

4. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study

Author

Fehringer, Gordon, Brenner, Darren R, Zhang, Zuo‐Feng, Lee, Yuan‐Chin Amy, Matsuo, Keitaro, Ito, Hidemi, Lan, Qing, Vineis, Paolo, Johansson, Mattias, Overvad, Kim, Riboli, Elio, Trichopoulou, Antonia, Sacerdote, Carlotta, Stucker, Isabelle, Boffetta, Paolo, Brennan, Paul, Christiani, David C, Hong, Yun‐Chul, Landi, Maria Teresa, Morgenstern, Hal, Schwartz, Ann G, Wenzlaff, Angela S, Rennert, Gad, McLaughlin, John R, Harris, Curtis C, Olivo‐Marston, Susan, Orlow, Irene, Park, Bernard J, Zauderer, Marjorie, Dios, Juan M Barros, Raviña, Alberto Ruano, Siemiatycki, Jack, Koushik, Anita, Lazarus, Philip, Fernández‐Somoano, Ana, Tardon, Adonina, Le Marchand, Loic, Brenner, Hermann, Saum, Kai‐Uwe, Duell, Eric J, Andrew, Angeline S, Szeszenia‐Dabrowska, Neonila, Lissowska, Jolanta, Zaridze, David, Rudnai, Peter, Fabianova, Eleonora, Mates, Dana, Foretova, Lenka, Janout, Vladimir, Bencko, Vladimir, Holcatova, Ivana, Pesatori, Angela Cecilia, Consonni, Dario, Olsson, Ann, Straif, Kurt, and Hung, Rayjean J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Lung, Cancer, Substance Misuse, Tobacco, Alcoholism, Alcohol Use and Health, Tobacco Smoke and Health, Prevention, Lung Cancer, Cardiovascular, Stroke, Respiratory, Good Health and Well Being, Aged, Alcohol Drinking, Alcoholic Beverages, Asia, Case-Control Studies, Cohort Studies, Europe, Female, Humans, Lung Neoplasms, Male, Middle Aged, North America, Risk Factors, Smoking, alcohol, lung cancer, wine, beer, liquor, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

Published
2017

7. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors

Author

Kasi, Pashtoon M., Fehringer, Gordon, Taniguchi, Hiroya, Starling, Naureen, Nakamura, Yoshiaki, Kotani, Daisuke, Powles, Thomas, Li, Bob T., Pusztai, Lajos, Aushev, Vasily N., Kalashnikova, Ekaterina, Sharma, Shruti, Malhotra, Meenakshi, Demko, Zachary P., Aleshin, Alexey, Rodriguez, Angel, Billings, Paul R., Grothey, Axel, Taieb, Julien, Cunningham, David, Yoshino, Takayuki, and Kopetz, Scott

Published
2022
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8. A two-dimensional pooling strategy for rare variant detection on next-generation sequencing platforms.

Author

Zuzarte, Philip C, Denroche, Robert E, Fehringer, Gordon, Katzov-Eckert, Hagit, Hung, Rayjean J, and McPherson, John D

Subjects
Humans, Sequence Analysis, DNA, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, General Science & Technology
Abstract

We describe a method for pooling and sequencing DNA from a large number of individual samples while preserving information regarding sample identity. DNA from 576 individuals was arranged into four 12 row by 12 column matrices and then pooled by row and by column resulting in 96 total pools with 12 individuals in each pool. Pooling of DNA was carried out in a two-dimensional fashion, such that DNA from each individual is present in exactly one row pool and exactly one column pool. By considering the variants observed in the rows and columns of a matrix we are able to trace rare variants back to the specific individuals that carry them. The pooled DNA samples were enriched over a 250 kb region previously identified by GWAS to significantly predispose individuals to lung cancer. All 96 pools (12 row and 12 column pools from 4 matrices) were barcoded and sequenced on an Illumina HiSeq 2000 instrument with an average depth of coverage greater than 4,000×. Verification based on Ion PGM sequencing confirmed the presence of 91.4% of confidently classified SNVs assayed. In this way, each individual sample is sequenced in multiple pools providing more accurate variant calling than a single pool or a multiplexed approach. This provides a powerful method for rare variant detection in regions of interest at a reduced cost to the researcher.

Published
2014

9. Sensitive tumour detection and classification using plasma cell-free DNA methylomes

Author

Shen, Shu Yi, Singhania, Rajat, Fehringer, Gordon, Chakravarthy, Ankur, Roehrl, Michael H. A., Chadwick, Dianne, Zuzarte, Philip C., Borgida, Ayelet, Wang, Ting Ting, Li, Tiantian, Kis, Olena, Zhao, Zhen, Spreafico, Anna, Medina, Tiago da Silva, Wang, Yadon, Roulois, David, Ettayebi, Ilias, Chen, Zhuo, Chow, Signy, Murphy, Tracy, Arruda, Andrea, O’Kane, Grainne M., Liu, Jessica, Mansour, Mark, McPherson, John D., O’Brien, Catherine, Leighl, Natasha, Bedard, Philippe L., Fleshner, Neil, Liu, Geoffrey, Minden, Mark D., Gallinger, Steven, Goldenberg, Anna, Pugh, Trevor J., Hoffman, Michael M., Bratman, Scott V., Hung, Rayjean J., and De Carvalho, Daniel D.

Published
2018
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10. Supplementary Table 1 from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author

Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary

Published
2023
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11. Data from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author

Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary

Published
2023
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12. Supplementary Table 2 and Supplemental Figures from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author

Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary

Published
2023
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13. Supplementary Material: Funding, Acknowledgements, Consortia, and Bioinformatics Tools Funding sources from Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Author

Fehringer, Gordon, primary, Kraft, Peter, primary, Pharoah, Paul D., primary, Eeles, Rosalind A., primary, Chatterjee, Nilanjan, primary, Schumacher, Fredrick R., primary, Schildkraut, Joellen M., primary, Lindström, Sara, primary, Brennan, Paul, primary, Bickeböller, Heike, primary, Houlston, Richard S., primary, Landi, Maria Teresa, primary, Caporaso, Neil, primary, Risch, Angela, primary, Amin Al Olama, Ali, primary, Berndt, Sonja I., primary, Giovannucci, Edward L., primary, Grönberg, Henrik, primary, Kote-Jarai, Zsofia, primary, Ma, Jing, primary, Muir, Kenneth, primary, Stampfer, Meir J., primary, Stevens, Victoria L., primary, Wiklund, Fredrik, primary, Willett, Walter C., primary, Goode, Ellen L., primary, Permuth, Jennifer B., primary, Risch, Harvey A., primary, Reid, Brett M., primary, Bezieau, Stephane, primary, Brenner, Hermann, primary, Chan, Andrew T., primary, Chang-Claude, Jenny, primary, Hudson, Thomas J., primary, Kocarnik, Jonathan K., primary, Newcomb, Polly A., primary, Schoen, Robert E., primary, Slattery, Martha L., primary, White, Emily, primary, Adank, Muriel A., primary, Ahsan, Habibul, primary, Aittomäki, Kristiina, primary, Baglietto, Laura, primary, Blomquist, Carl, primary, Canzian, Federico, primary, Czene, Kamila, primary, dos-Santos-Silva, Isabel, primary, Eliassen, A. Heather, primary, Figueroa, Jonine D., primary, Flesch-Janys, Dieter, primary, Fletcher, Olivia, primary, Garcia-Closas, Montserrat, primary, Gaudet, Mia M., primary, Johnson, Nichola, primary, Hall, Per, primary, Hazra, Aditi, primary, Hein, Rebecca, primary, Hofman, Albert, primary, Hopper, John L., primary, Irwanto, Astrid, primary, Johansson, Mattias, primary, Kaaks, Rudolf, primary, Kibriya, Muhammad G., primary, Lichtner, Peter, primary, Liu, Jianjun, primary, Lund, Eiliv, primary, Makalic, Enes, primary, Meindl, Alfons, primary, Müller-Myhsok, Bertram, primary, Muranen, Taru A., primary, Nevanlinna, Heli, primary, Peeters, Petra H., primary, Peto, Julian, primary, Prentice, Ross L., primary, Rahman, Nazneen, primary, Sanchez, Maria Jose, primary, Schmidt, Daniel F., primary, Schmutzler, Rita K., primary, Southey, Melissa C., primary, Tamimi, Rulla, primary, Travis, Ruth C., primary, Turnbull, Clare, primary, Uitterlinden, Andre G., primary, Wang, Zhaoming, primary, Whittemore, Alice S., primary, Yang, Xiaohong R., primary, Zheng, Wei, primary, Buchanan, Daniel D., primary, Casey, Graham, primary, Conti, David V., primary, Edlund, Christopher K., primary, Gallinger, Steven, primary, Haile, Robert W., primary, Jenkins, Mark, primary, Le Marchand, Loïc, primary, Li, Li, primary, Lindor, Noralene M., primary, Schmit, Stephanie L., primary, Thibodeau, Stephen N., primary, Woods, Michael O., primary, Rafnar, Thorunn, primary, Gudmundsson, Julius, primary, Stacey, Simon N., primary, Stefansson, Kari, primary, Sulem, Patrick, primary, Chen, Y. Ann, primary, Tyrer, Jonathan P., primary, Christiani, David C., primary, Wei, Yongyue, primary, Shen, Hongbing, primary, Hu, Zhibin, primary, Shu, Xiao-Ou, primary, Shiraishi, Kouya, primary, Takahashi, Atsushi, primary, Bossé, Yohan, primary, Obeidat, Ma'en, primary, Nickle, David, primary, Timens, Wim, primary, Freedman, Matthew L., primary, Li, Qiyuan, primary, Seminara, Daniela, primary, Chanock, Stephen J., primary, Gong, Jian, primary, Peters, Ulrike, primary, Gruber, Stephen B., primary, Amos, Christopher I., primary, Sellers, Thomas A., primary, Easton, Douglas F., primary, Hunter, David J., primary, Haiman, Christopher A., primary, Henderson, Brian E., primary, and Hung, Rayjean J., primary

Published
2023
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14. Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant

Author

Rosenheck, Justin P., primary, Ross, David J., additional, Botros, Mena, additional, Wong, Alexander, additional, Sternberg, Jonathan, additional, Chen, Yen-An, additional, Liang, Nathan, additional, Baer, Amy, additional, Ahmed, Ebad, additional, Swenerton, Ryan, additional, Zimmermann, Bernhard G., additional, Fehringer, Gordon, additional, Demko, Zachary P., additional, Olymbios, Michael, additional, Billings, Paul R., additional, and Keller, Brian C., additional

Published
2022
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16. Identification of shared and unique susceptibility pathways among cancers of the lung, breast, and prostate from genome-wide association studies and tissue-specific protein interactions

Author

Qian, David C., Byun, Jinyoung, Han, Younghun, Greene, Casey S., Field, John K., Hung, Rayjean J., Brhane, Yonathan, Mclaughlin, John R., Fehringer, Gordon, Landi, Maria Teresa, Rosenberger, Albert, Bickeböller, Heike, Malhotra, Jyoti, Risch, Angela, Heinrich, Joachim, Hunter, David J., Henderson, Brian E., Haiman, Christopher A., Schumacher, Fredrick R., Eeles, Rosalind A., Easton, Douglas F., Seminara, Daniela, and Amos, Christopher I.

Published
2015
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20. Abstract 569: Correlation of variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

Author

Tin, Antony, primary, Aushev, Vasily, additional, Kalashnikova, Ekaterina, additional, Salari, Raheleh, additional, Shchegrova, Svetalana, additional, Fehringer, Gordon, additional, Malhotra, Meenakshi, additional, Ravi, Harini, additional, Sethi, Himanshu, additional, Brevnov, Maxim, additional, Zimmermann, Bernhard, additional, Rodriguez, Angel, additional, Billings, Paul R., additional, and Aleshin, Alexey, additional

Published
2021
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25. An international comparison of cancer survival: Toronto, Ontario, and Detroit, Michigan, metropolitan areas

Author

Gorey, Kevin M., Holowaty, Eric J., Fehringer, Gordon, Laukkanen, Ethan, Moskowitz, Agnes, Webster, David J., and Richter, Nancy L.

Subjects
Cancer survivors -- Economic aspects, Social status -- Health aspects, Government, Health care industry
Abstract

Objectives. This study examined whether socioeconomic status has a differential effect on the survival of adults diagnosed with cancer in Canada and the United States. Methods. The Ontario Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program provided a total of 58 202 and 76 055 population-based primary malignant cancer cases for Toronto, Ontario, and Detroit, Mich, respectively. Socioeconomic data for each person's residence at time of diagnosis were taken from population censuses. Results. In the US cohort, there was a significant association between socioeconomic status and survival for 12 of the 15 most common cancer sites; in the Canadian cohort, there was no such association for 12 of the 15 sites. Among residents of low-income areas, persons in Toronto experienced a survival advantage for 13 of 15 cancer sites at 1- and 5-year follow-up. No such between-country differentials were observed in the middle- or high-income groups. Conclusions. The consistent pattern of a survival advantage in Canada observed across various cancer sites and follow-up periods suggests that Canada's more equitable access to preventive and therapeutic health care services is responsible for the difference. (Am J Public Health. 1997;87: 1156-1163)

Published
1997

27. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study

Author

Fehringer, Gordon Brenner, Darren R. Zhang, Zuo-Feng Lee, Yuan-Chin Amy Matsuo, Keitaro Ito, Hidemi Lan, Qing and Vineis, Paolo Johansson, Mattias Overvad, Kim Riboli, Elio and Trichopoulou, Antonia Sacerdote, Carlotta Stucker, Isabelle and Boffetta, Paolo Brennan, Paul Christiani, David. C. and Hong, Yun-Chul Landi, Maria Teresa Morgenstern, Hal and Schwartz, Ann G. Wenzlaff, Angela S. Rennert, Gad and McLaughlin, John R. Harris, Curtis C. Olivo-Marston, Susan and Orlow, Irene Park, Bernard J. Zauderer, Marjorie Barros Dios, Juan M. Ruano Ravina, Alberto Siemiatycki, Jack and Koushik, Anita Lazarus, Philip Fernandez-Somoano, Ana and Tardon, Adonina Le Marchand, Loic Brenner, Hermann Saum, Kai-Uwe Duell, Eric J. Andrew, Angeline S. and Szeszenia-Dabrowska, Neonila Lissowska, Jolanta Zaridze, David and Rudnai, Peter Fabianova, Eleonora Mates, Dana Foretova, Lenka Janout, Vladimir Bencko, Vladimir Holcatova, Ivana and Pesatori, Angela Cecilia Consonni, Dario Olsson, Ann Straif, Kurt Hung, Rayjean J.

Abstract

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

Published
2017

28. Alcohol and lung cancer risk among never smokers: A pooledanalysis from the international lung cancer consortium and the SYNERGY study

Author

Fehringer, Gordon, Brenner, Darren R., Zhang, Zuo-Feng, Lee, Y. A., Matsuo, Keitaro, Ito, Hidemi, Lan, Qing, Fernández Somoano, Ana, and Tardón García, Adonina

Subjects
education, Wine, Alcohol, Lung, health care economics and organizations, Cancer
Abstract

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance, Grant sponsor: Canadian Cancer Society; Grant number: CCSRI no. 020214; Grant sponsor: Ministry of Education, Science, Sports, Culture and Technology of Japan (AICHI: MEXT Kakenhi); Grant numbers: 170150181 and 26253041; Grant sponsor: European Commission’s INCO-COPERNICUS Program; Grant number: IC15-CT96-0313; Grant sponsor: National Institutes of Health; Grant numbers: NIH R01CA060691, NIH R01CA87895, NIH P30CA022453, NIH P30 CA008748, HHSN261201200011; Grant sponsor: National Cancer Institute; Grant numbers: CA092824, CA074386, CA090578; Grant sponsor: FIS-FEDER/Spain; Grant numbers: FIS-01/310, FISPI03-0365, and FIS-07-BI060604; Grant sponsor: FICYT/Asturias; Grant numbers: FICYT PB02-67, FICYT IB09-133; Grant sponsor: National Center for Research Resources; Grant number: P20RR018787; Grant sponsor: Research Intention PRVOUK; Grant number: PRVOUK P28/1LF/6; Grant sponsors: Intramural Research Program of the National Institutes of Health; Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan; Steps for Breath, the Labrecque Foundation and the Society of Memorial Sloan-Kettering Cancer Center; The University of Oviedo, Asturias, Spain; The Fundacion Caja de Ahorros de Asturias and the Ciber de Epidemiologia y Salud Publica, CIBERESP, Spain; Baden-Wurttemberg State Ministry of Research, Science and Arts; Danish Cancer Society, Fehringer, G., Brenner, D.R., Zhang, Z.-F., Lee, Y.-C.A., Matsuo, K., Ito, H., Lan, Q., Vineis, P., Johansson, M., Overvad, K., Riboli, E., Trichopoulou, A., Sacerdote, C., Stucker, I., Boffetta, P., Brennan, P., Christiani, D.C., Hong, Y.-C., Landi, M.T., Morgenstern, H., Schwartz, A.G., Wenzlaff, A.S., Rennert, G., McLaughlin, J.R., Harris, C.C., Olivo-Marston, S., Orlow, I., Park, B.J., Zauderer, M., Barros Dios, J.M., Ruano Raviña, A., Siemiatycki, J., Koushik, A., Lazarus, P., Fernández-Somoano, A., Tardon, A., Le Marchand, L., Brenner, H., Saum, K.-U., Duell, E.J., Andrew, A.S., Szeszenia-Dabrowska, N., Lissowska, J., Zaridze, D., Rudnai, P., Fabianova, E., Mates, D., Foretova, L., Janout, V., Bencko, V., Holcatova, I., Pesatori, A.C., Consonni, D., Olsson, A., Straif, K., Hung, R.J.

Published
2017

29. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Author

Fehringer, Gordon, Kraft, Peter, Pharoah, Paul D, Eeles, Rosalind A, Chatterjee, Nilanjan, Schumacher, Fredrick R, Schildkraut, Joellen M, Lindstrom, Sara, Brennan, Paul, Bickeboller, Heike, Houlston, Richard S, Landi, Maria Teresa, Caporaso, Neil, Risch, Angela, Al Olama, Ali Amin, Berndt, Sonja I, Giovannucci, Edward L, Gronberg, Henrik, Kote-Jarai, Zsofia, Ma, Jing, Muir, Kenneth, Stampfer, Meir J, Stevens, Victoria L, Wiklund, Fredrik, Willett, Walter C, Goode, Ellen L, Permuth, Jennifer B, Risch, Harvey A, Reid, Brett M, Bezieau, Stephane, Brenner, Hermann, Chan, Andrew T, Chang-Claude, Jenny, Hudson, Thomas J, Kocarnik, Jonathan K, Newcomb, Polly A, Schoen, Robert E, Slattery, Martha L, White, Emily, Adank, Muriel A, Ahsan, Habibul, Aittomaki, Kristiina, Baglietto, Laura, Blomquist, Carl, Canzian, Federico, Czene, Kamila, dos-Santos-Silva, Isabel, Eliassen, A Heather, Figueroa, Jonine D, Flesch-Janys, Dieter, Fletcher, Olivia, Garcia-Closas, Montserrat, Gaudet, Mia M, Johnson, Nichola, Hall, Per, Hazra, Aditi, Hein, Rebecca, Hofman, Albert, Hopper, John L, Irwanto, Astrid, Johansson, Mattias, Kaaks, Rudolf, Kibriya, Muhammad G, Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Meindl, Alfons, Muller-Myhsok, Bertram, Muranen, Taru A, Nevanlinna, Heli, Peeters, Petra H, Peto, Julian, Prentice, Ross L, Rahman, Nazneen, Sanchez, Maria Jose, Schmidt, Daniel F, Schmutzler, Rita K, Southey, Melissa C, Tamimi, Rulla, Travis, Ruth C, Turnbull, Clare, Uitterlinden, Andre G, Wang, Zhaoming, Whittemore, Alice S, Yang, Xiaohong R, Zheng, Wei, Buchanan, Daniel D, Casey, Graham, Conti, David V, Edlund, Christopher K, Gallinger, Steven, Haile, Robert W, Jenkins, Mark, Le Marchand, Loic, Li, Li, Lindor, Noralene M, Schmit, Stephanie L, Thibodeau, Stephen N, Woods, Michael O, Rafnar, Thorunn, Gudmundsson, Julius, Stacey, Simon N, Stefansson, Kari, Sulem, Patrick, Chen, Y Ann, Tyrer, Jonathan P, Christiani, David C, Wei, Yongyue, Shen, Hongbing, Hu, Zhibin, Shu, Xiao-Ou, Shiraishi, Kouya, Takahashi, Atsushi, Bosse, Yohan, Obeidat, Ma'en, Nickle, David, Timens, Wim, Freedman, Matthew L, Li, Qiyuan, Seminara, Daniela, Chanock, Stephen J, Gong, Jian, Peters, Ulrike, Gruber, Stephen B, Amos, Christopher I, Sellers, Thomas A, Easton, Douglas F, Hunter, David J, Haiman, Christopher A, Henderson, Brian E, Hung, Rayjean J, OCAC, Consortium, PRACTICAL, Res, Hereditary Breast Ovarian Canc, Transdisciplinary, Colorectal, Canc, African Amer Breast, Canc, African Ancestry Prostate, Medical Oncology, Epidemiology, Internal Medicine, Surgery, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
0301 basic medicine, Oncology, Male, medicine.medical_specialty, Cancer Research, Lung Neoplasms, SUSCEPTIBILITY LOCI, Genotype, IDENTIFIES 2, Colorectal cancer, Locus (genetics), Genome-wide association study, Breast Neoplasms, Article, 03 medical and health sciences, Prostate cancer, AFRICAN ANCESTRY, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Journal Article, AGGRESSIVE PROSTATE, Humans, GENETIC POLYMORPHISMS, Lung cancer, METAANALYSIS, Ovarian Neoplasms, business.industry, COMMON VARIANTS, Prostatic Neoplasms, CELL CARCINOMA, medicine.disease, RISK LOCI, 3. Good health, 030104 developmental biology, Expression quantitative trait loci, Adenocarcinoma, Female, business, Colorectal Neoplasms, GASTRIC-CANCER, Genome-Wide Association Study
Abstract

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.

Published
2016

30. Cross-Cancer Analysis Reveals Novel Pleiotropic Associations—Response

Author

Hung, Rayjean J., primary, Fehringer, Gordon, additional, Casey, Graham, additional, Gruber, Stephen B., additional, Peters, Ulrike, additional, Goode, Ellen L., additional, Sellers, Thomas A., additional, Haiman, Christopher A., additional, Hunter, David J., additional, Kraft, Peter, additional, Amos, Christopher I., additional, Freedman, Matthew L., additional, and Wilson, Michael D., additional

Published
2017
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31. PLoS ONE / META-GSA : Combining Findings from Gene-Set Analyses across several genome-wide association studies

Author

Rosenberger, Albert, Friedrichs, Stefanie, Amos, Christopher I., Brennan, Paul, Fehringer, Gordon, Heinrich, Joachim, Hung, Rayjean J., Muley, Thomas, Müller-Nurasyid, Martina, Risch, Angela, and Bickeböller, Heike

Subjects
Meta-analysis, Permutation, Test statistics, Lung and intrathoracic tumors, Principal component analysis, Genome-wide association studies, Gene pool, Statistical distributions
Abstract

Introduction: Gene-set analysis (GSA) methods are used as complementary approaches to genome-wide association studies (GWASs). The single marker association estimates of a predefined set of genes are either contrasted with those of all remaining genes or with a null non-associated background. To pool the p-values from several GSAs, it is important to take into account the concordance of the observed patterns resulting from single marker association point estimates across any given gene set. Here we propose an enhanced version of Fishers inverse 2-method META-GSA, however weighting each study to account for imperfect correlation between association patterns. Simulation and Power: We investigated the performance of META-GSA by simulating GWASs with 500 cases and 500 controls at 100 diallelic markers in 20 different scenarios, simulating different relative risks between 1 and 1.5 in gene sets of 10 genes. Wilcoxons rank sum test was applied as GSA for each study. We found that META-GSA has greater power to discover truly associated gene sets than simple pooling of the p-values, by e.g. 59% versus 37%, when the true relative risk for 5 of 10 genes was assume to be 1.5. Under the null hypothesis of no difference in the true association pattern between the gene set of interest and the set of remaining genes, the results of both approaches are almost uncorrelated. We recommend not relying on p-values alone when combining the results of independent GSAs. Application: We applied META-GSA to pool the results of four case-control GWASs of lung cancer risk (Central European Study and Toronto/Lunenfeld-Tanenbaum Research Institute Study; German Lung Cancer Study and MD Anderson Cancer Center Study), which had already been analyzed separately with four different GSA methods (EASE; SLAT, mSUMSTAT and GenGen). This application revealed the pathway GO0015291 “transmembrane transporter activity” as significantly enriched with associated genes (GSA-method: EASE, p = 0.0315 corrected for multiple testing). Similar results were found for GO0015464 “acetylcholine receptor activity” but only when not corrected for multiple testing (all GSA-methods applied; p0.02). (VLID)1844043

Published
2015

32. META-GSA: Combining findings from gene-set analyses across several genome-wide association studies

Author

Rosenberger, Albert, Friedrichs, Stefanie, Amos, Christopher I., Brennan, Paul, Fehringer, Gordon, Heinrich, Joachim, Hung, Rayjean J., Muley, Thomas, Müller-Nurasyid, Martina, Risch, Angela, and Bickeböller, Heike

Subjects
Genetic Markers, Genome-wide association studies, Test statistics, Meta-analysis, Permutation, Lung and intrathoracic tumors, Statistical distributions, Principal component analysis, Gene pool, lcsh:R, lcsh:Medicine, Models, Theoretical, Statistics, Nonparametric, Genes, Meta-Analysis as Topic, Humans, Genetic Predisposition to Disease, lcsh:Q, lcsh:Science, Alleles, Research Article, Genome-Wide Association Study
Abstract

INTRODUCTION: Gene-set analysis (GSA) methods are used as complementary approaches to genome-wide association studies (GWASs). The single marker association estimates of a predefined set of genes are either contrasted with those of all remaining genes or with a null non-associated background. To pool the p-values from several GSAs, it is important to take into account the concordance of the observed patterns resulting from single marker association point estimates across any given gene set. Here we propose an enhanced version of Fisher's inverse χ2-method META-GSA, however weighting each study to account for imperfect correlation between association patterns. SIMULATION AND POWER: We investigated the performance of META-GSA by simulating GWASs with 500 cases and 500 controls at 100 diallelic markers in 20 different scenarios, simulating different relative risks between 1 and 1.5 in gene sets of 10 genes. Wilcoxon's rank sum test was applied as GSA for each study. We found that META-GSA has greater power to discover truly associated gene sets than simple pooling of the p-values, by e.g. 59% versus 37%, when the true relative risk for 5 of 10 genes was assume to be 1.5. Under the null hypothesis of no difference in the true association pattern between the gene set of interest and the set of remaining genes, the results of both approaches are almost uncorrelated. We recommend not relying on p-values alone when combining the results of independent GSAs. APPLICATION: We applied META-GSA to pool the results of four case-control GWASs of lung cancer risk (Central European Study and Toronto/Lunenfeld-Tanenbaum Research Institute Study; German Lung Cancer Study and MD Anderson Cancer Center Study), which had already been analyzed separately with four different GSA methods (EASE; SLAT, mSUMSTAT and GenGen). This application revealed the pathway GO0015291 "transmembrane transporter activity" as significantly enriched with associated genes (GSA-method: EASE, p = 0.0315 corrected for multiple testing). Similar results were found for GO0015464 "acetylcholine receptor activity" but only when not corrected for multiple testing (all GSA-methods applied; p≈0.02). Open-Access Publikationsfonds 2015 peerReviewed

Published
2015

33. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

Author

Epidemiology & Health Economics, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Fehringer, Gordon, Kraft, Peter, Pharoah, Paul D., Eeles, Rosalind A., Chatterjee, Nilanjan, Schumacher, Fredrick R., Schildkraut, Joellen M., Lindström, Sara, Brennan, Paul, Bickeböller, Heike, Houlston, Richard S., Landi, Maria Teresa, Caporaso, Neil, Risch, Angela, Al Olama, Ali Amin, Berndt, Sonja I., Giovannucci, Edward L., Grönberg, Henrik, Kote-Jarai, Zsofia, Ma, Jing, Muir, Kenneth, Stampfer, Meir J., Stevens, Victoria L., Wiklund, Fredrik, Willett, Walter C., Goode, Ellen L., Permuth, Jennifer B., Risch, Harvey A., Reid, Brett M., Bezieau, Stephane, Brenner, Hermann, Chan, Andrew T., Chang-Claude, Jenny, Hudson, Thomas J., Kocarnik, Jonathan K., Newcomb, Polly A., Schoen, Robert E., Slattery, Martha L., White, Emily, Adank, Muriel A., Ahsan, Habibul, Aittomäki, Kristiina, Baglietto, Laura, Blomquist, Carl, Canzian, Federico, Czene, Kamila, Dos-Santos-silva, Isabel, Eliassen, A. Heather, Figueroa, Jonine D., Flesch-Janys, Dieter, Fletcher, Olivia, Garcia-Closas, Montserrat, Gaudet, Mia M., Johnson, Nichola, Hall, Per, Hazra, Aditi, Hein, Rebecca, Hofman, Albert, Hopper, John L., Irwanto, Astrid, Johansson, Mattias, Kaaks, Rudolf, Kibriya, Muhammad G., Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Meindl, Alfons, Müller-Myhsok, Bertram, Muranen, Taru A., Nevanlinna, Heli, Peeters, Petra H., Peto, Julian, Prentice, Ross L., Rahman, Nazneen, Sanchez, Maria Jose, Schmidt, Daniel F., Schmutzler, Rita K., Southey, Melissa C., Tamimi, Rulla, Travis, Ruth C., Turnbull, Clare, Uitterlinden, Andre G., Wang, Zhaoming, Whittemore, Alice S., Yang, Xiaohong R., Zheng, Wei, Buchanan, Daniel D., Casey, Graham, Conti, David V., Edlund, Christopher K., Gallinger, Steven, Haile, Robert W., Jenkins, Mark, Marchand, Loïcle, Li, Li, Lindor, Noralene M., Schmit, Stephanie L., Thibodeau, Stephen N., Woods, Michael O., Rafnar, Thorunn, Gudmundsson, Julius, Stacey, Simon N., Stefansson, Kari, Sulem, Patrick, Chen, Y. Ann, Tyrer, Jonathan P., Christiani, David C., Wei, Yongyue, Shen, Hongbing, Hu, Zhibin, Shu, Xiao Ou, Shiraishi, Kouya, Takahashi, Atsushi, Bossé, Yohan, Obeidat, Ma'en, Nickle, David, Timens, Wim, Freedman, Matthew L., Li, Qiyuan, Seminara, Daniela, Chanock, Stephen J., Gong, Jian, Peters, Ulrike, Gruber, Stephen B., Amos, Christopher I., Sellers, Thomas A., Easton, Douglas F., Hunter, David J., Haiman, Christopher A., Henderson, Brian E., Hung, Rayjean J., Epidemiology & Health Economics, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Fehringer, Gordon, Kraft, Peter, Pharoah, Paul D., Eeles, Rosalind A., Chatterjee, Nilanjan, Schumacher, Fredrick R., Schildkraut, Joellen M., Lindström, Sara, Brennan, Paul, Bickeböller, Heike, Houlston, Richard S., Landi, Maria Teresa, Caporaso, Neil, Risch, Angela, Al Olama, Ali Amin, Berndt, Sonja I., Giovannucci, Edward L., Grönberg, Henrik, Kote-Jarai, Zsofia, Ma, Jing, Muir, Kenneth, Stampfer, Meir J., Stevens, Victoria L., Wiklund, Fredrik, Willett, Walter C., Goode, Ellen L., Permuth, Jennifer B., Risch, Harvey A., Reid, Brett M., Bezieau, Stephane, Brenner, Hermann, Chan, Andrew T., Chang-Claude, Jenny, Hudson, Thomas J., Kocarnik, Jonathan K., Newcomb, Polly A., Schoen, Robert E., Slattery, Martha L., White, Emily, Adank, Muriel A., Ahsan, Habibul, Aittomäki, Kristiina, Baglietto, Laura, Blomquist, Carl, Canzian, Federico, Czene, Kamila, Dos-Santos-silva, Isabel, Eliassen, A. Heather, Figueroa, Jonine D., Flesch-Janys, Dieter, Fletcher, Olivia, Garcia-Closas, Montserrat, Gaudet, Mia M., Johnson, Nichola, Hall, Per, Hazra, Aditi, Hein, Rebecca, Hofman, Albert, Hopper, John L., Irwanto, Astrid, Johansson, Mattias, Kaaks, Rudolf, Kibriya, Muhammad G., Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Meindl, Alfons, Müller-Myhsok, Bertram, Muranen, Taru A., Nevanlinna, Heli, Peeters, Petra H., Peto, Julian, Prentice, Ross L., Rahman, Nazneen, Sanchez, Maria Jose, Schmidt, Daniel F., Schmutzler, Rita K., Southey, Melissa C., Tamimi, Rulla, Travis, Ruth C., Turnbull, Clare, Uitterlinden, Andre G., Wang, Zhaoming, Whittemore, Alice S., Yang, Xiaohong R., Zheng, Wei, Buchanan, Daniel D., Casey, Graham, Conti, David V., Edlund, Christopher K., Gallinger, Steven, Haile, Robert W., Jenkins, Mark, Marchand, Loïcle, Li, Li, Lindor, Noralene M., Schmit, Stephanie L., Thibodeau, Stephen N., Woods, Michael O., Rafnar, Thorunn, Gudmundsson, Julius, Stacey, Simon N., Stefansson, Kari, Sulem, Patrick, Chen, Y. Ann, Tyrer, Jonathan P., Christiani, David C., Wei, Yongyue, Shen, Hongbing, Hu, Zhibin, Shu, Xiao Ou, Shiraishi, Kouya, Takahashi, Atsushi, Bossé, Yohan, Obeidat, Ma'en, Nickle, David, Timens, Wim, Freedman, Matthew L., Li, Qiyuan, Seminara, Daniela, Chanock, Stephen J., Gong, Jian, Peters, Ulrike, Gruber, Stephen B., Amos, Christopher I., Sellers, Thomas A., Easton, Douglas F., Hunter, David J., Haiman, Christopher A., Henderson, Brian E., and Hung, Rayjean J.

Published
2016

34. Abstract 817: Mendelian randomization and mediation analysis of 5p15.33, telomere length and lung cancer risk

Author

Kachuri, Linda, primary, Davey Smith, George, additional, Liu, Geoffrey, additional, Landi, Maria Teresa, additional, Christiani, David C., additional, Caporaso, Neil E., additional, McKay, James D., additional, Wu, Xifeng, additional, Aldrich, Melinda C., additional, Rennert, Gad, additional, Teare, Dawn, additional, Chen, Chu, additional, Goodman, Gary E., additional, Doherty, Jennifer A., additional, Field, John K., additional, Kiemeney, Lambertus A., additional, Tardón, Adonina, additional, Haugen, Aage, additional, Lam, Stephen, additional, Le Marchand, Loic, additional, Schabath, Matthew B., additional, Andrew, Angeline S., additional, Johansson, Mattias, additional, Manjer, Jonas, additional, Lazarus, Philip, additional, Arnold, Susanne, additional, Fehringer, Gordon, additional, Zong, Xuchen, additional, Brennan, Paul, additional, Bojesen, Stig E., additional, Amos, Christopher I., additional, and Hung, Rayjean J., additional

Published
2016
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36. Abstract 1274: Alcohol and lung cancer risk: a pooled analysis using International Lung Cancer Consortium studies

Author

Fehringer, Gordon, primary, Brenner, Darren, additional, Zhang, Zuo-Feng, additional, Lee, Yuan-Chin Amy, additional, Matsuo, Keitaro, additional, Stucker, Isabelle, additional, Vineis, Paolo, additional, Boffetta, Paolo, additional, Brennan, Paul, additional, Landi, Maria T., additional, Morgenstern, Hal, additional, Harris, Curtis C., additional, Lan, Qing, additional, Hong, Yun-Chul, additional, Siemiatycki, Jack, additional, McLaughlin, John R., additional, Lazarus, Philip, additional, Muscat, Joshua, additional, Schwartz, Ann G., additional, Dios, Juan M. Barros, additional, Raviña, Alberto R., additional, Rennert, Gad, additional, Christiani, David C., additional, Tardon, Adonina, additional, Marchand, Loic L., additional, Orlow, Irene, additional, Duell, Eric J., additional, Andrew, Angeline S., additional, Brenner, Hermann, additional, Consonni, Dario, additional, Olsson, Ann, additional, Straif, Kurt, additional, and Hung, Rayjean J., additional

Published
2014
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39. Abstract 4210: Association of the 15q25 and 5p15 lung cancer susceptibility regions with gene expression in lung tumor tissue

Author

Fehringer, Gordon, primary, Liu, Geoffrey, additional, Pintilie, Melania, additional, Sykes, Jenna, additional, Liu, Ni, additional, Cheng, Dangxiao, additional, Chen, Zhuo, additional, Seymour, Lesley, additional, Der, Sandy D., additional, Shepherd, Frances A., additional, Tsao, Ming-Sound, additional, and Hung, Rayjean J., additional

Published
2012
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44. Family-based genetic association study of insulin-like growth factor I microsatellite markers and premenopausal breast cancer risk.

Author

Fehringer, Gordon, Boyd, Norman, Knight, Julia, Paterson, Andrew, Dite, Gillian, Giles, Graham, Southey, Melissa, Andrulis, Irene, Hopper, John, and Ozcelik, Hilmi

Abstract

Several studies suggest that higher circulating insulin-like growth factor I (IGF-I) levels are associated with premenopausal breast cancer risk. Breast cancer risk and circulating IGF-I concentration appear to be partly heritable, thus genetic variation at IGF1 could influence IGF-I levels and breast cancer risk. We investigated the association of IGF1 CA repeat variants with premenopausal breast cancer risk using a family-based design. The study sample included 840 families from the Ontario Familial Breast Cancer Registry (OFBCR) and the Australian Breast Cancer Family Registry (ABCFR). Three CA repeat variants, at 5′, 3′, and in intron 2 were genotyped (5′CA, 3′CA, In2CA). We found several nominally significant associations. The 5′CA-21 allele ( P = 0.03) and In2CA-212 allele ( P = 0.04) were associated with lower risk, and the In2CA-216 allele with higher risk ( P = 0.04) for the combined ABCFR–OFBCR. These associations were not significant after taking into account multiple comparisons. In2CA-216 was more strongly associated with risk when we used a recessive instead of an additive model ( P = 0.01). 5′CA alleles of repeat length 18–20 were associated with higher risk ( P = 0.02), and 5′CA alleles of >20 repeats were associated with lower risk ( P = 0.01). These associations were significant in the OFBCR (In2CA-216 recessive, P = 0.02; 5′CA 18–20 and >20 allele grouping, P = 0.01) but not strongly supported by the ABCFR (In2CA-216 recessive, P = 0.14; 5′CA 18–20, P = 0.25; 5′CA >20, P = 0.20). The associations we found could be due to chance as many comparisons were made. Our results do not strongly support an association between these IGF1 variants and breast cancer risk. [ABSTRACT FROM AUTHOR]

Published
2010
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46. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

Author

Fehringer G, Kraft P, Pharoah PD, Eeles RA, Chatterjee N, Schumacher FR, Schildkraut JM, Lindström S, Brennan P, Bickeböller H, Houlston RS, Landi MT, Caporaso N, Risch A, Amin Al Olama A, Berndt SI, Giovannucci EL, Grönberg H, Kote-Jarai Z, Ma J, Muir K, Stampfer MJ, Stevens VL, Wiklund F, Willett WC, Goode EL, Permuth JB, Risch HA, Reid BM, Bezieau S, Brenner H, Chan AT, Chang-Claude J, Hudson TJ, Kocarnik JK, Newcomb PA, Schoen RE, Slattery ML, White E, Adank MA, Ahsan H, Aittomäki K, Baglietto L, Blomquist C, Canzian F, Czene K, Dos-Santos-Silva I, Eliassen AH, Figueroa JD, Flesch-Janys D, Fletcher O, Garcia-Closas M, Gaudet MM, Johnson N, Hall P, Hazra A, Hein R, Hofman A, Hopper JL, Irwanto A, Johansson M, Kaaks R, Kibriya MG, Lichtner P, Liu J, Lund E, Makalic E, Meindl A, Müller-Myhsok B, Muranen TA, Nevanlinna H, Peeters PH, Peto J, Prentice RL, Rahman N, Sanchez MJ, Schmidt DF, Schmutzler RK, Southey MC, Tamimi R, Travis RC, Turnbull C, Uitterlinden AG, Wang Z, Whittemore AS, Yang XR, Zheng W, Buchanan DD, Casey G, Conti DV, Edlund CK, Gallinger S, Haile RW, Jenkins M, Le Marchand L, Li L, Lindor NM, Schmit SL, Thibodeau SN, Woods MO, Rafnar T, Gudmundsson J, Stacey SN, Stefansson K, Sulem P, Chen YA, Tyrer JP, Christiani DC, Wei Y, Shen H, Hu Z, Shu XO, Shiraishi K, Takahashi A, Bossé Y, Obeidat M, Nickle D, Timens W, Freedman ML, Li Q, Seminara D, Chanock SJ, Gong J, Peters U, Gruber SB, Amos CI, Sellers TA, Easton DF, Hunter DJ, Haiman CA, Henderson BE, and Hung RJ

Subjects
Female, Genome-Wide Association Study, Genotype, Humans, Male, Breast Neoplasms genetics, Colorectal Neoplasms genetics, Lung Neoplasms genetics, Ovarian Neoplasms genetics, Prostatic Neoplasms genetics
Abstract

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR., Competing Interests: of Potential Conflicts of Interest: Dr. David Nickle is a full time employee at Merck & Co. No potential conflicts of interest were disclosed by other authors., (©2016 American Association for Cancer Research.)

Published
2016
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