title: Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xi
authors.affiliation: Tianxin District Center for Disease Control and Prevention, Changsha, Hunan Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Su
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37220, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly Fadiel
authors.affiliation: First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Feng-Xi
authors.initials: FX
authors.lastname: Su
authors.affiliation: Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Lu-Ying
authors.initials: LY
authors.lastname: Tang
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address: renzef@mail.sysu.edu.cn.
authors.forename: Ze-Fang
authors.initials: ZF
authors.lastname: Ren
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Breast cancer; DNA methylation; Fibroblast growth factor receptor 2; Physical activity; Polymorphisms