Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non‐small cell lung cancer

Abstract

Background Both genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non‐tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied. Methods We selected 410 non‐small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription‐PCR was performed to detect ALK , ROS1 , RET , and NTRK1 rearrangement. Results Among the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty‐seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4‐ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure. Conclusion FLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

Overall and cause-specific mortality rates among men and women with high exposure to indoor air pollution from the use of smoky and smokeless coal: a cohort study in Xuanwei, China

“… 11 24 Previous research has also indicated that clinicopathologic features including gene fusion patterns of lung cancer in this population may be distinct from other populations that have less or no exposure to coal combustion. 25 26 While proximity to coal communes in XW play a role in lung cancer burden, it is the specific constituents of the coal found in this region that is the driver of lung cancer and other diseases. For example, a population-based case–control study of lung cancer cases among never-smoking women in XW found that a cluster of 25 PAHs had the strongest association with lung cancer of 43 different household air pollutants evaluated.…”

Connexins in Lung Cancer and Brain Metastasis

“…Furthermore, it is important to study lung cancer metastasis in the environmental context with potential lung carcinogens, such as coal combustion emissions. The findings of such investigations on the Cx isoforms and lung cancer types should be compared to global geographic variations, as reflected by the lung cancer rate in Xuanwei, China, which is the highest in the world ( 71 , 72 ). Extrapolating knowledge from studies on Cxs from other cancer types, to lung cancer and brain metastasis may also foster the development of more effective therapeutic approaches.…”

Genetic differences between smokers and never-smokers with lung cancer

“…However, in the high lung cancer prevalence Xuanwei area in China, mentioned erlier, it was found in 12.4% of NSCLC patients (7.9% men, 21.8% women). The highest EML4-ALK rate (35.1%, 33/94) occurred in female patients with both familial lung cancer (FLC) history and high tobacco and coal smoke exposure ( 25 ). CD74-ROS1 fusions were less frequent than EML4-ALK ( 24 , 25 ).…”

“…The highest EML4-ALK rate (35.1%, 33/94) occurred in female patients with both familial lung cancer (FLC) history and high tobacco and coal smoke exposure ( 25 ). CD74-ROS1 fusions were less frequent than EML4-ALK ( 24 , 25 ). The consequences of each mutation or other genetic alteration are frequently dependent on molecular changes already present in the cell.…”