Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning

Howard D. Hosgood, William Pao, Nathaniel Rothman, Wei Hu, Yumei Helen Pan, Kyle Kuchinsky, Kirk D. Jones, Jun Xu, Roel Vermeulen, Jeff Simko, Qing Lan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1755-1762
Number of pages8
JournalRespiratory Medicine
Volume107
Issue number11
DOIs
StatePublished - Nov 2013

Fingerprint

Coal
China
Lung Neoplasms
Smoking
Mutation
Exons
Indoor Air Pollution
Mutation Rate
Point Mutation
Neoplasms
Adenosquamous Carcinoma
Population
Squamous Cell Carcinoma
Adenocarcinoma
Lung
Genes

Keywords

  • China
  • Driver mutations
  • EGFR
  • KRAS
  • Lung cancer
  • Never smoking

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning. / Hosgood, Howard D.; Pao, William; Rothman, Nathaniel; Hu, Wei; Pan, Yumei Helen; Kuchinsky, Kyle; Jones, Kirk D.; Xu, Jun; Vermeulen, Roel; Simko, Jeff; Lan, Qing.

In: Respiratory Medicine, Vol. 107, No. 11, 11.2013, p. 1755-1762.

Research output: Contribution to journalArticle

Hosgood, Howard D. ; Pao, William ; Rothman, Nathaniel ; Hu, Wei ; Pan, Yumei Helen ; Kuchinsky, Kyle ; Jones, Kirk D. ; Xu, Jun ; Vermeulen, Roel ; Simko, Jeff ; Lan, Qing. / Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning. In: Respiratory Medicine. 2013 ; Vol. 107, No. 11. pp. 1755-1762.
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abstract = "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.",
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