Interactions of cigarette smoking, ESR2, GPER1, IGF-1 and EPO genetic polymorphisms on lung cancer development

• Main Authors: Ya-Jun Chen, 陳雅君
• Other Authors: Chiu-Ying Chen
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/k7v299

碩士 === 中國醫藥大學 === 公共衛生學系碩士班 === 106 === Lung cancer is an important cancer, and smoking is the major risk factor for lung cancer. Especially, compounds in cigarettes may induce downstream gene expressions through the estrogen receptor β (ER-β, ESR2). The transmembrane G protein-coupled estrogen receptor 1 (GPER1) can conduct rapid non-genomic effects and induce cell proliferation and differentiation, and a multi-faceted network of messages can be generated with insulin-like growth factors (IGFs), triggering gene expression changes, cell proliferation, migration, and survival. The expressions of erythropoietin (EPO) and its receptor are also regulated by estrogen, thus affecting proliferation, metastasis, invasion, and apoptosis of cancer cells. Therefore, we designed a case-control study to assess the interactions of cigarette smoking, ESR2, GPER1, IGF-1 and EPO genotypes on lung cancer development. A total of 250 primary lung cancer cases and 500 healthy controls were recruited in this study. Questionnaires were used to collect demographic characteristics, smoking habits, green tea consumption, intake of fruits and vegetables, cooking practices, and lung cancer family history. Genotypes were identified by the polymerase chain reaction. Results showed, compared to subjects who carrying GPER1 rs3808351 GG, IGF-1 (CA)19/(CA)19+(CA)19/X, and EPO rs576236 TT genotypes, those carrying GPER1 AA+AG (OR = 3.39, 95% C.I. = 1.80-6.37), IGF-1 X/X (OR = 1.74, 95% C.I. = 1.19-6.55), and EPO CC+CT genotypes (OR = 1.53, 95% C.I. = 1.10-2.12) had a significantly higher risk of lung cancer, respectively. Compared to men with non-susceptible genotypes of GPER1, IGF1, and EPO, women carrying susceptible genotypes have significantly higher risk of lung cancer, respectively. In addition, there were significant interactions between smoking and ESR2, GPER1, and EPO genotypes on the risk of lung cancer development, respectively. Our overall results suggest that the individual’s estrogen-related effect may be related to the occurrence of lung cancer and explain the developmental differences in gender.