A Study Of Lung Adenocarcinoma Gene Mutations In Non-Smoking Women In Xuanwei Area

Objective:To investigate the mutation rate,mutation characteristics and clinical distribution of different mutation types in major driver genes in non-smoking female lung adenocarcinoma patients in Xuanwei,Yunnan Province,to explore the possible molecular characteristics of the high prevalence of non-smoking female lung adenocarcinoma in Xuanwei,and to suggest the potential for improved clinical individualized targeted therapy for non-smoking female adenocarcinoma patients in Xuanwei.Method:Genetic testing cases of lung adenocarcinoma pathology specimens sent by the Department of Thoracic Surgery between January 2018 and December 2021 were retrieved through the data management system of the Molecular Diagnostic Center of Yunnan Cancer Hospital,and the genetic testing results and clinical data of a total of1907 non-smoking female lung adenocarcinoma patients were included according to the nadir criteria,and all patients gave their informed consent.Statistical analysis was performed using the SPSS 26.0 statistical package.The differences between the general clinical characteristics(age,TNM stage,family history of lung cancer,lymph node metastasis,tumor location,and tumor diameter)of the Xuanwei group and the non-Xuanwei group were analyzed for the 1907 included patients according to the region of case origin.Subsequently,we analyzed the driver gene mutations in 1907patients in depth,first analyzing the differences in driver gene mutations between Xuanwei and non-Xuanwei female lung adenocarcinoma patients,exploring the molecular characteristics of non-smoking female adenocarcinoma in Xuanwei,and then further investigating the clinical characteristics of driver genes with different mutation profiles between Xuanwei and non-Xuanwei populations.Results:1.The clinical characteristics of 1907 non-smoking female lung adenocarcinoma patients were analyzed according to the regional classification of case origin.605(31.73%)of the 1907 patients were Xuanwei cases(defined as those whose ancestral origin was located in Xuanwei for three or more generations).The differences in age,TNM stage,family history of lung cancer,and tumor diameter between the Xuanwei and non-Xuanwei groups were statistically significant(P<0.05).The differences in lymph node metastasis and location of tumor occurrence were not statistically significant(P>0.05).Adenocarcinoma in non-smoking women in the Xuanwei group had younger age of onset(P<0.001),earlier stage(more patients with stage Ⅰ-Ⅱ)(x~2=31.235 P<0.001),more family history of lung cancer(x~2=92.133 P<0.001),and smaller tumor diameter than in the non-Xuanwei group(x~2=14.44 P<0.001).2.Genetic mutations were detected in 1470(77.08%)of 1907 non-smoking female adenocarcinomas,covering the eight genotypes recommended by the guidelines for testing,including 1091(57.21%)EGFR mutations,205(10.75%)KRAS mutations,59(3.09%)ALK mutations,30(1.57%)MET mutations,28(1.47%)BRAF mutations,22(1.15%)ROS1 mutations,20(1.05%)HER-2 mutations,15(0.79%)RET mutations,and the other 437 patients were not found to have these mutations.EGFR was the most frequent driver mutation type in both the Xuanwei and non-Xuanwei groups.Meanwhile,the frequency of KRAS mutations was higher in the Xuanwei group than in the non-Xuanwei group(13.55%VS9.45%,P<0.01difference was statistically significant);the frequency of ALK mutations was higher in the Xuanwei group than in the non-Xuanwei group(4.46%VS2.46%,P<0.05difference was statistically significant).The difference between the Xuanwei group and the non-Xuanwei group in the mutation rates of 19-Del,G719S,S768I,G719C+S768I,G719A+S768I,G719A+L861Q was were statistically significant.The frequency of rare mutations(mutations other than L858R and 19-Del)was 60.45%in the Xuanwei group and 47.27%in the non-Xuanwei group(x~2=14.568 P<0.001),compared with the non-Xuanwei group,the Xuanwei group was dominated by rare mutation types and had a higher rate of rare mutations,while the classical EGFR common mutations with lower mutation frequency.3.The EGFR mutation rate in non-smoking female lung adenocarcinoma patients was higher in younger(P<0.001),TNM stage Ⅰ-Ⅱ(x~2=287.376 P<0.001),family history of lung cancer(x~2=33.848 P<0.001)and tumor diameter>3 cm(x~2=4.336 P<0.05)were higher;while EGFR mutation rate was not associated with lymph node metastasis status(P>0.05).Non-smoking female lung adenocarcinoma patients with positive EGFR mutations were younger in the Xuanwei group(P<0.001)and had more family history of lung cancer than those in the non-Xuanwei group(x~2=34.079P<0.001);the differences in TNM stage,lymph node metastasis,and tumor diameter between the two groups were not statistically significant(P>0.05).4.The KRAS mutation rate in non-smoking female lung adenocarcinoma patients was higher in those who were younger(P<0.001)and had a family history of lung cancer(x~2=4.494 P<0.05);while the differences in mutation rate in TNM stage,tumor diameter,and lymph node metastasis were not statistically significant(P>0.05).The KRAS mutation-positive non-smoking female lung There were more family histories of lung cancer in the Xuanwei group than in the non-Xuanwei group(x~2=12.528 P<0.001);the differences in age,TNM stage,lymph node metastasis,and tumor diameter between the two groups were not statistically significant(P>0.05).5.The ALK mutation rate in non-smoking female lung adenocarcinoma patients was higher in those who were younger(P<0.001)and had lymph node metastasis(x~2=6.362 P<0.05);the differences in mutation rate in TNM stage,family history of lung cancer,and tumor diameter were not statistically significant(P>0.05).In non-smoking female lung adenocarcinoma patients with positive ALK mutation The differences between the Xuanwei and non-Xuanwei groups in age,family history of lung cancer,TNM stage,lymph node metastasis,and tumor diameter were not statistically significant(P>0.05).Conclusion:1.clinical characteristics of non-smoking female lung adenocarcinoma patients:lower median age in the Xuanwei group than in the non-Xuanwei group,more stage Ⅰ-Ⅱ patients in the Xuanwei group,more family history of lung cancer exhibited,and more patients with tumor diameter≤3 cm.2.EGFR gene mutation rate was highest in non-smoking female lung adenocarcinoma patients,followed by KRAS and ALK genes;in terms of EGFR mutation type,Xuanwei non-smoking The mutation type of female adenocarcinoma patients with rare mutations was predominant,and their mutation rate was higher than that of the non-Xuanwei population.3.Among non-smoking female lung adenocarcinoma patients,the EGFR mutation rate was higher in patients who were young,had TNM stage Ⅰ-Ⅱ,had family history,and had tumor diameter>3 cm.The median age of non-smoking female lung adenocarcinoma patients with EGFR mutation was lower in the Xuanwei group than in the non-Xuanwei group and the Xuanwei group showed more family history of lung cancer than the non-Xuanwei group.4.The rate of KRAS mutation was higher in non-smoking female lung adenocarcinoma patients who were younger and had a family history.In non-smoking female lung adenocarcinoma patients with KRAS mutations,the Xuanwei group had a higher incidence of family history of lung cancer than the non-Xuanwei group.5.In non-smoking female lung adenocarcinoma patients,the rate of ALK mutations was higher in younger patients with lymph node metastasis.