Background: Many previous studies reported secular trend of lung cancer incidence and mortality, but little is known about the possible reasons for these trends. Methods: Data were obtained from Shanghai Cancer Registry. Age-standardized rates were calculated and average annual percent changes (AAPCs) were evaluated by Joinpoint regression. Age, period, and birth cohort effects were assessed by ageperiod-cohort models. Results: From 1973 to 2010, compared with long-time slowly increasing trend in women, male lung cancer incidence had significantly decreased between 2001 and 2009. After that lung cancer incidence rising sharply in women (AAPC = 14.13%, 95%CI: 2.68%-26.86%, P = .016) and similar rising trends without statistical significance in men (AAPC = 2.96, 95%CI: −2.47%-8.69%, P = .281) between 2010 and 2014. Age-period cohort model showed the different patterns of period effects for lung cancer incidence between men and women. The period effects for lung cancer incidence showed rising effect for women, whereas there was decline effect for lung cancer incidence for men. On the other hand, the model showed a significant period effect in both genders with a similar fashion in mortality, yielding steady falling trends during the entire study period. Conclusions: The distinctive patterns of lung cancer incidence between men and women may be attributable to significant period effects, which reflected the changes in public health policies or diagnostic practices and highlighted the urgent of continued monitoring of gender-specific risk factors for lung cancer incidence. K E Y W O R D Sage-period-cohort model, gender disparity, incidence, Lung cancer, mortality | 2931 XIE Et al.

BackgroundLung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.MethodsWe obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.ResultsWe found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD.ConclusionsThe expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.

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