Table 1.
Comparison of Demographics, Xuanwei Smoky Coal Exposure and Genomic Features of Lung Adenocarcinoma Tumors in Cases from Xuanwei, Kunming, and the Pan-Cancer Analysis of Whole Genomes Study
| Xuanwei | Kunming | PCAWG | PCAWG | |
|---|---|---|---|---|
| Nonsmokers | Nonsmokers | Smokers | Nonsmokers | |
| (n = 18) | (n = 6) | (n = 21) | (n = 17) | |
| Demographics and coal exposure* | ||||
| Age, yr, median (range) | 55 (44–64) | 61 (52–66) | 70 (41–81) | 64 (52–79) |
| Sex, M/F | 1/17 | 0/6 | 13/8 | 5/12 |
| Cumulative tons Xuanwei smoky coal burned in home before age 18 yr, median (range) | 102 (3–170) | 0 | 0 | 0 |
| Cumulative tons Xuanwei smoky coal burned in home age ⩾18 yr, median (range) | 130 (0–364) | 0 | 0 | 0 |
| Tumor molecular characteristics | ||||
| Tumor mutational burden† (median) | 7.55 | 1.05 | 13.15 | 1.63 |
| Percentage of genomic alterations by copy number, median | 79% | 84% | 84% | 78% |
| Structural variants, median | 77 | 92 | 66 | 71 |
| Whole-genome doubling, no. of tumors (%) | 11 (61.11%) | 4 (66.67%) | 12 (57.14%) | 11 (64.75%) |
| Kataegis,‡ no. of tumors (%) | 10 (55.55%) | 3 (50.00%) | 14 (66.67%) | 8 (47.06%) |
| Tumor driver mutations, no. of tumors (%) | ||||
| EGFR mutation | 12 (66.67%) | 3 (50.00%) | 2 (9.52%) | 3 (17.65%) |
| EGFR (double mutations) | 7 (38.89%) | 0 (0%) | 0 (0%) | 1 (5.88%) |
| EGFR (hotspot) | p.S768I, 8 (44.44%) | p.L858R, 2 (33.33%) | No hotspot | No hotspot |
| KRAS mutation | 1 (5.56%) | 0 (0%) | 5 (23.81%) | 2 (11.76%) |
| TP53 mutation | 9 (50.0%) | 1 (16.67%) | 11 (52.38%) | 4 (23.53%) |
| SFTPB (noncoding) | 2 (11.11%) | 0 (0%) | 3 (14.29%) | 1 (5.88%) |
| ALK (fusion) | 0 (0%) | 2 (33.33%) | 0 (0%) | 0 (0%) |
| CDKN2A deletion | 5 (27.78%) | 0 (0%) | 3 (14.29%) | 3 (17.65%) |
| Tumor mutational signatures,§ median no. (%) mutations assigned to each signature | ||||
| COSMIC Signature SBS4 | 18,646 (80.3%) | 0 (0%) | 26,887 (69.9%) | 0 (0%) |
| COSMIC Signature DBS2 | 106 (47.44%) | — | 781 (100%) | — |
| COSMIC Signature ID3 | 644 (100%) | — | 1,007 (100%) | — |
Definition of abbreviations: DBS = doublet base substitution; ID = insertions and deletions; SBS = single base substitution.
No cases from Xuanwei or Kunming had a history of tuberculosis. Nine of 18 cases from Xuanwei and no cases from Kunming had a family history of lung cancer. One of 18 cases from Xuanwei and no cases from Kunming had a history of previous noncancer lung disease. Seventeen of 18 and 2 of 6 cases from Xuanwei and Kunming, respectively, had a history of exposure to environmental tobacco smoke. Seventeen of 18 cases from Xuanwei had lived in a home where smoky coal combustion was not ventilated to the outside by a chimney. None of these variables were statistically significantly associated with the mutational signatures presented in the table and were not included in analytical models. Tumor stage: Xuanwei (seven IA, three IB, two IIA, four IIIA); Kunming (one IA, three IB, one IIA, one IIB).
Tumor mutational burden estimated as the number of mutations per megabase.
Kataegis, a pattern of localized hypermutations identified in cancer genomes.
Signature deconvolution analysis performed by SigProfilerExtractor algorithm and using COSMIC mutational signatures version 3 as reference (10); COSMIC: Catalogue of Somatic Mutations in Cancer (https://cancer.sanger.ac.uk/signatures).