Accepted Manuscript Germline mutations in DNA repair genes in lung adenocarcinoma Erin M. Parry, Dustin L. Gable, Susan E. Stanley, Sara E. Khalil, Valentin Antonescu, Liliana Florea, Mary Armanios PII:
S1556-0864(17)30686-X
DOI:
10.1016/j.jtho.2017.08.011
Reference:
JTHO 681
To appear in:
Journal of Thoracic Oncology
Received Date: 14 July 2017 Revised Date:
31 July 2017
Accepted Date: 5 August 2017
Please cite this article as: Parry EM, Gable DL, Stanley SE, Khalil SE, Antonescu V, Florea L, Armanios M, Germline mutations in DNA repair genes in lung adenocarcinoma, Journal of Thoracic Oncology (2017), doi: 10.1016/j.jtho.2017.08.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Journal of Thoracic Oncology
RI PT
Germline mutations in DNA repair genes in lung adenocarcinoma
Correspondence
EP
Mary Armanios, M.D. 1650 Orleans St. CRB 1 Room 186 Baltimore, MD 21287 Phone 410-502-3817 Fax 410-502-6240
TE D
M AN U
Osler Medical Housestaff Training Program1, Medical Scientist Training Program3, Departments of Medicine2 and Oncology4, Sidney Kimmel Comprehensive Cancer Center6, and McKusick-Nathans Institute of Genetic Medicine5 Johns Hopkins University School of Medicine Baltimore, MD 21287
SC
Erin M. Parry1,2*, Dustin L. Gable3,4,5, Susan E. Stanley3,4,5, Sara E. Khalil4,5, Valentin Antonescu2,5, Liliana Florea2,5, Mary Armanios4,5,6
AC C
[email protected]
Funding: This work was supported by NIH grants CA160433 and HL119476, the Commonwealth Foundation and the Maryland Cigarette Restitution Fund (to M.A.) and NSF ABI-1356078 (to L.F.). Disclosures: The authors declare no relevant conflicts of interest. *Dr. Parry’s current affiliation is with the Dana-Farber/Partners Cancer Care Oncology Fellowship Program, Boston, MA
1
ACCEPTED MANUSCRIPT
Abstract
RI PT
Introduction: While lung cancer is generally thought to be environmentally provoked, anecdotal familial clustering has been reported suggesting there may be genetic susceptibility factors. We systematically tested whether germline mutations in eight candidate genes may be risk factors for lung adenocarcinoma. Methods: We studied lung adenocarcinoma cases for whom germline sequence data had been generated as part of The Cancer Genome Atlas (TCGA) project, but that had not been previously analyzed. We selected eight genes, ATM, BRCA2, CHEK2, EGFR, PARK2, TERT, TP53, and YAP1, based on prior anecdotal association with lung cancer or genome wide association studies.
M AN U
SC
Results: Among 555 lung adenocarcinoma cases, we detected 14 pathogenic mutations in five genes; they occurred at a frequency of 2.5% and represented an odds ratio of 66 (95 confidence interval, 33 to 125, P
S1556-0864(17)30686-X
DOI:
10.1016/j.jtho.2017.08.011
Reference:
JTHO 681
To appear in:
Journal of Thoracic Oncology
Received Date: 14 July 2017 Revised Date:
31 July 2017
Accepted Date: 5 August 2017
Please cite this article as: Parry EM, Gable DL, Stanley SE, Khalil SE, Antonescu V, Florea L, Armanios M, Germline mutations in DNA repair genes in lung adenocarcinoma, Journal of Thoracic Oncology (2017), doi: 10.1016/j.jtho.2017.08.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Journal of Thoracic Oncology
RI PT
Germline mutations in DNA repair genes in lung adenocarcinoma
Correspondence
EP
Mary Armanios, M.D. 1650 Orleans St. CRB 1 Room 186 Baltimore, MD 21287 Phone 410-502-3817 Fax 410-502-6240
TE D
M AN U
Osler Medical Housestaff Training Program1, Medical Scientist Training Program3, Departments of Medicine2 and Oncology4, Sidney Kimmel Comprehensive Cancer Center6, and McKusick-Nathans Institute of Genetic Medicine5 Johns Hopkins University School of Medicine Baltimore, MD 21287
SC
Erin M. Parry1,2*, Dustin L. Gable3,4,5, Susan E. Stanley3,4,5, Sara E. Khalil4,5, Valentin Antonescu2,5, Liliana Florea2,5, Mary Armanios4,5,6
AC C
[email protected]
Funding: This work was supported by NIH grants CA160433 and HL119476, the Commonwealth Foundation and the Maryland Cigarette Restitution Fund (to M.A.) and NSF ABI-1356078 (to L.F.). Disclosures: The authors declare no relevant conflicts of interest. *Dr. Parry’s current affiliation is with the Dana-Farber/Partners Cancer Care Oncology Fellowship Program, Boston, MA
1
ACCEPTED MANUSCRIPT
Abstract
RI PT
Introduction: While lung cancer is generally thought to be environmentally provoked, anecdotal familial clustering has been reported suggesting there may be genetic susceptibility factors. We systematically tested whether germline mutations in eight candidate genes may be risk factors for lung adenocarcinoma. Methods: We studied lung adenocarcinoma cases for whom germline sequence data had been generated as part of The Cancer Genome Atlas (TCGA) project, but that had not been previously analyzed. We selected eight genes, ATM, BRCA2, CHEK2, EGFR, PARK2, TERT, TP53, and YAP1, based on prior anecdotal association with lung cancer or genome wide association studies.
M AN U
SC
Results: Among 555 lung adenocarcinoma cases, we detected 14 pathogenic mutations in five genes; they occurred at a frequency of 2.5% and represented an odds ratio of 66 (95 confidence interval, 33 to 125, P
