RESUMEN

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.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carbón Mineral/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Fusión Génica , Neoplasias Pulmonares/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/genética , China/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Masculino , Anamnesis , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret/genética , Receptor trkA/genética

RESUMEN

BACKGROUND: Lung cancer induced by burning coal can be etiologically and clinically different from lung cancer caused by smoking. Despite previous work, the gene fusion patterns in lung cancer patients affected by household coal combustion still deserve further study. METHODS: Non-small cell lung cancer (NSCLC) patients exposed to household coal use (HCU) were recruited from rural areas in China's Yunnan Province, certain areas in this region had notably high lung cancer rate nationwide. Reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of ALK, ROS1, RET and NTRK1 rearrangements. Eighteen studies on ALK fusions were summarized and compared with present work. RESULTS: Among the 205 patients, there were 112 (54.6%) coal users and 96 (46.8%) smokers, union set had 145 (70.7%) subjects, in which 63 (30.7%) were double-positive for HCU and smoking. HCU patients featured with younger age and advanced stage. Union set patients covered larger age span (range, 40-82 years old), showed clear early-onset, and made the majority of stage IIIA-IV cases. Double-positive individuals were mainly in later stage, but with wider age span (range, 38-75 years old). In addition, 18 patients (8.8%) had EML4-ALK rearrangement, with apparently higher-than-average variant 3 ratio (77.8% vs. 44%). Five ROS1 fusion cases (2.5%) were identified, all were CD74-ROS1 (E6/E34), and had HCU experience. ALK and ROS1 fusions were mutually exclusive. Both ALK fusions and total gene rearrangement events (ALK and ROS1) showed association with HCU and overall exposure (tobacco and coal). Suggesting there could be unique gene fusion patterns in lung cancer patients affected by coal use. CONCLUSIONS: Present study found clinic-pathologic features and gene fusion patterns in NSCLC showed association with household coal combustion. Our findings may help evaluate the impact of coal use on the pathogenesis of lung cancer, and also highlight the significance of integrating different exposure histories into clinical and theoretical research.

RESUMEN

Background: Lung cancer has inherited susceptibility and show familial aggregation, the characteristics of familial lung cancer exhibit population heterogeneity. Despite previous studies, familial lung cancer in China's Yunnan-Guizhou plateau remains understudied. Methods: Between 2015 and 2017, 1,023 lung cancer patients (residents of Yunnan-Guizhou plateau) were enrolled with no limitation on other parameters, 152 subjects had familial lung cancer. Clinicopathologic parameters were analyzed and compared, 4,754 lung cancer patients from NCI-GDC were used to represent a general population. Results: Familial lung cancer (FLC) subjects showed unique characters: early-onset; increased rate of female, adenocarcinoma, stage IV and other cancer history; unbalance in anatomic sites; all ruling out significant difference in smoking status. Unbalanced distribution of co-existing diseases or symptoms was also discovered. FLC patients were more likely to develop benign lesions (polyps, nodules, cysts) early in life, especially early-growth of multiple pulmonary nodules at higher frequency. Typical diseases with family history like diabetes and hypertension were also increased in FLC population. Compared to GDC data, our subject population was younger: the age peak of our FLC group was in 50-59; our sporadic group had an age peak around 60; while GDC patients' age peak was in 60-69. Importantly, the biggest difference happened in age 40-49: our FLC group and sporadic group had 3 times and 2 times higher ratio than GDC population, respectively. Moreover, the age peaks of our FLC males and FLC females were both in 50-59; while our sporadic females had the age peak in 50-59, much earlier than sporadic males (around 60-69); reflecting gender-specific or age-specific characters in our subject population. Conclusions: Familial lung cancer in China's Yunnan-Guizhou plateau showed unique clinicopathologic characters, differences were found in gender, age, histologic type, TNM stage and co-existing diseases or symptoms. Identification of hereditary factors which lead to increased lung cancer risk will be a challenge of both scientific and clinical significance.