Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning.
Lung cancer in never smokers, which has been partially attributed to household solid fuel use (i.e., coal), is etiologically and clinically different from lung cancer attributed to tobacco smoking. To explore the spectrum of driver mutations among lung cancer tissues from never smokers, specifically in a population where high lung cancer rates have been attributed to indoor air pollution from domestic coal use, multiplexed assays were used to detect >40 point mutations, insertions, and deletions (EGFR, KRAS, BRAF, HER2, NRAS, PIK3CA, MEK1, AKT1, and PTEN) among the lung tumors of confirmed never smoking females from Xuanwei, China [32 adenocarcinomas (ADCs), 7 squamous cell carcinomas (SCCs), 1 adenosquamous carcinoma (ADSC)]. EGFR mutations were detected in 35% of tumors. 46% of these involved EGFR exon 18 G719X, while 14% were exon 21 L858R mutations. KRAS mutations, all of which were G12C_34G>T, were observed in 15% of tumors. EGFR and KRAS mutations were mutually exclusive, and no mutations were observed in the other tested genes. Most point mutations were transversions and were also found in tumors from patients who used coal in their homes. Our high mutation frequencies in EGFR exon 18 and KRAS and low mutation frequency in EGFR exon 21 are strikingly divergent from those in other smoking and never smoking populations from Asia. Given that our subjects live in a region where coal is typically burned indoors, our findings provide new insights into the pathogenesis of lung cancer among never smoking females exposed to indoor air pollution from coal.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, MD, USA; Division of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: dean.hosgood@einstein.yu.edu.
H Dean
HD
Hosgood
William
W
Pao
Nathaniel
N
Rothman
Wei
W
Hu
Yumei Helen
YH
Pan
Kyle
K
Kuchinsky
Kirk D
KD
Jones
Jun
J
Xu
Roel
R
Vermeulen
Jeff
J
Simko
Qing
Q
Lan
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000328:Adult; D016902:Air Pollution, Indoor / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D003031:Coal / Q000009:adverse effects; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012906:Smoke / Q000009:adverse effects; D012907:Smoking; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
D003031:Coal; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012906:Smoke; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
China; Driver mutations; EGFR; KRAS; Lung cancer; Never smoking