Genetic variants in one-carbon metabolism genes and breast cancer risk in European American (EA) and African American (AA) women

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Gong, Zhihong ; Yao, Song ; Zirpoli, Gary ; Cheng, Ting-Yuan David ; Roberts, Michelle ; Khoury, Thaer ; Ciupak, Gregory ; Davis, Warren ; Pawlish, Karen ; Jandorf, Lina ; Bovbjerg, Dana H. ; Bandera, Elisa V. ; Ambrosone, Christine B.
• Description:
  Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299 African-American (AA) women who participated in the Women's Circle of Health Study. Allele frequencies varied significantly between EA and AA populations. A number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS and SLC19A1, were associated with overall breast cancer risk, as well as risk by estrogen receptor (ER) status, in either EA or AA women. Associations appeared to be modified by dietary folate intake. Although single-SNP associations were not statistically significant after correcting for multiple comparisons, polygenetic score analyses revealed significant associations with breast cancer risk. Per unit increase of the risk score was associated with a modest 19 to 50% increase in risk of breast cancer overall, ER positive or ER negative cancer (all p < 0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing gene polymorphisms could play a role in breast cancer and that may differ between EA and AA women.
• Subjects:
  Adult Alleles Black People Breast Neoplasms Case-Control Studies Diet Europe Female Folic Acid Gene Frequency Genetic Predisposition To Disease Genetic Variation Genotype Humans Middle Aged Multifactorial Inheritance Odds Ratio Polymorphism, Single Nucleotide Population Surveillance Receptors, Estrogen Risk Risk Factors United States

  More +
• Keywords:
  African American Breast Cancer European American One-carbon Metabolism Polymorphisms
• Source:
  Int J Cancer. 137(3):666-677
• Pubmed ID:
  25598430
• Pubmed Central ID:
  PMC4437886
• Document Type:
  Journal Article
• Funding:
  U58 DP003931/DP/NCCDPHP CDC HHSUnited States/ ; P30 CA016056/CA/NCI NIH HHSUnited States/ ; K07 CA178293/CA/NCI NIH HHSUnited States/ ; P30 CA072720/CA/NCI NIH HHSUnited States/ ; P01 CA151135/CA/NCI NIH HHSUnited States/ ; K22 CA138563/CA/NCI NIH HHSUnited States/ ; HHSN261201300021C/CA/NCI NIH HHSUnited States/ ; R01 CA100598/CA/NCI NIH HHSUnited States/
• Volume:
  137
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ff10bd5f678c6cec27dcca94f47fbcc7a09b136a009f7a746d8a227af3ca7f0f
• Download URL:
  https://stacks.cdc.gov/view/cdc/42042/cdc_42042_DS1.pdf
• File Type:
  [PDF - 755.71 KB ]