Jing Xi1, Yi Su2, Alicia Beeghly Fadiel3, Ying Lin4, Feng-Xi Su5, Wei-Hua Jia6, Lu-Ying Tang7, Ze-Fang Ren8. 1. School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China. 2. Tianxin District Center for Disease Control and Prevention, Changsha, Hunan Province, China. 3. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37220, USA. 4. First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. 5. Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. 6. Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China. 7. Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. 8. School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address: renzef@mail.sysu.edu.cn.
Abstract
PURPOSE: Physical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk. METHODS: A total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models. RESULTS: Exercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2 rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28-4.35) compared to women with CC genotype and ≥ 3 MET-h/week/year. There was also a significant interaction between FGFR2 rs2981582 and MTHFR rs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively). CONCLUSION: We found both a gene-environment (FGFR2-exercise activity) and a gene-gene (FGFR2-MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast cancer.
PURPOSE: Physical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk. METHODS: A total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models. RESULTS: Exercise activity and FGFR2rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28-4.35) compared to women with CC genotype and ≥ 3 MET-h/week/year. There was also a significant interaction between FGFR2rs2981582 and MTHFRrs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively). CONCLUSION: We found both a gene-environment (FGFR2-exercise activity) and a gene-gene (FGFR2-MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast cancer.
Authors: Jin Shu; Xuelian Hui; Xin Zheng; Juan Zhao; Zhaochen Xu; Yingpu Chen; Chao Lu; Junling Li Journal: J Int Med Res Date: 2019-08-26 Impact factor: 1.671