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Environ Mol Mutagen. 2019 Aug;60(7):617-623. doi: 10.1002/em.22291. Epub 2019 May 8.

The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural china.

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Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong.
Qujing Center for Diseases Control and Prevention, Qujing, China.
Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China.
China National Environmental Monitoring Center, Beijing, China.
Maryland Institute for Applied Environmental Health, University of Maryland, School of Public Health, College Park, Maryland.


We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1-V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02-14.48], ORlow = 3.78 [1.03-13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67-8.48], ORlow = 2.01 [0.58-6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85-10.92], ORlow = 2.53 [0.72-8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42-3.66], ORlow = 2.01 [0.63-6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019.


animal contact; bacteria; cancer; coal; farm; lung; pulmonary

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