Household air pollution (HAP) and cancer – Dr. Dean Hosgood
Solid fuels (i.e., coal, wood) are often used for heating and cooking in unventilated situations within the home (i.e., rooms without a vent or stoves without a chimney), leading to substantial household air pollution (HAP) exposures, including to known carcinogens. HAP exposure is (1) experienced by ~3 billion people, (2) a leading cause of disease, and (3) causes >3.5 million deaths per year globally. Dr. Hosgood is recognized as one of the leading researchers in the world with respect to cancer risks attributed to HAP. He has published the definitive systematic reviews and meta-analyses evaluating the risk of lung cancer associated with HAP exposures. Some of the strongest literature evaluating lung cancer susceptibility attributed to HAP is based on studies in Xuanwei, China. Dr. Hosgood’s analysis of the Xuanwei residents’ coal burning has led to seminal findings on lung cancer and HAP. In a retrospective cohort study, Dr. Hosgood found that improving stoves to mitigate HAP exposure is associated with significant reductions in lung cancer mortality, even after accounting for exposure to second hand tobacco smoke. Largely influenced by this body of literature from Xuanwei, the International Agency for Research on Cancer (IARC) has concluded that indoor emissions from household combustion of coal are a lung carcinogen (Group 1).
A major focus of Dr. Hosgood’s research has been to elucidate the complex mechanisms underlying HAP-induced tumorigenesis. In case-control studies conducted in Xuanwei, Dr. Hosgood has observed that genetic variation in candidate immune, cell cycle, and telomere maintenance genes was associated with lung cancer risk. Dr. Hosgood and colleagues, though their research within the Female Lung Cancer Consortium in Asia (FLCCA), have also shown that lung cancer in nonsmokers (LCINS: ~25% of all lung cancer cases; 53% of those in women, 15% of those in men) has unique genetic risk factors when compared to lung cancer cases attributed to smoking tobacco. Notably, genome-wide association studies (GWAS), consisting primarily of smokers, identified susceptibility variants on 5p15 and 15q25, providing insights into the underlying mechanism(s) of lung cancer susceptibility. Dr. Hosgood and colleagues’ have shown that the nicotine receptor coding region on 15q25 was not associated with LCINS, and they have identified novel susceptibility loci, including HLA Class II, which were not associated with lung cancer risk (i.e., p≤10-8) in the GWAS consisting primarily of smokers. The risk of lung cancer associated with coal exposure varied with these novel loci, providing evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk (i.e., gene x environment interaction). In addition to genetic variation, Dr. Hosgood was the first to report that populations with substantial HAP exposures experience unique tumor-based EGFR and KRAS mutations patterns, as well as novel respiratory tract microbiota profiles, compared to other urban and rural populations.
Recently, Dr. Hosgood’s research has expanded into lung cancer-attributed to HAP in populations with low-dose, chronic exposures such as those in rural regions in the Northern United States, parts of Africa, and Chile. Dr. Hosgood has also built a global consortium of 13 prospective cohorts (HAPCO: Household Air Pollution Consortium) that have site- and disease-specific mortality and solid fuel use data, for a combined sample size of 587,257 participants across 8 countries, to date. HAPCO provides a novel opportunity to assess the risks associated with cancers other than lung as well as non-malignant respiratory and cardiometabolic outcomes, for which prospective epidemiologic research is limited.