Environmental Basis For Early Onset Breast Cancer.

Details

• Alternative Title:
  Reproductive Toxicology (Elmsford, N.Y.), 2025, v. 133: Environmental Basis For Early Onset Breast Cancer.
• Journal Article:
  Reproductive Toxicology (Elmsford, N.Y.)
• Personal Author:
  Teeny, Sami ; Jarrell, Zachery R. ; Krigbaum, Nickilou Y. ; Cirillo, Piera M. ; Go, Young-Mi ; Cohn, Barbara A. ; Jones, Dean P.
• Description:
  Pregnancy provokes a heightened amino acid requirement, especially in the third trimester. Alterations to late pregnancy amino acid metabolism have been associated with environmental breast carcinogen exposures, including DDT and PFAS. This project examined whether maternal serum amino acids in late pregnancy are associated with subsequent breast cancer risk. Archival third-trimester serum samples from 172 women who were later diagnosed with breast cancer were compared to samples from 351 women without known breast cancer. A prospective metabolome-wide association study (MWAS) for breast cancer cases showed that associated amino acid pathways included lysine, arginine, proline, aspartate, asparagine, alanine, tyrosine, tryptophan, histidine and branched-chain amino acids. Lower mean concentrations of individual amino acids, including histidine, threonine, lysine, and proline, were associated with an increased risk of breast cancer, and network analyses showed that these amino acids were negatively associated with protective breast cancer risk factors. Prospective MWAS for breast cancer cases diagnosed within 15 years of sample collection showed pathway associations for tryptophan, histidine, lysine methionine, and cysteine metabolism. Nutrient stresses caused by low amino acid levels impair immunosurveillance and activate oncogenic mechanisms of cell survival, thereby providing mechanisms by which environmental exposures in late pregnancy can contribute to breast cancer risk.
• Content Notes:
  Author manuscript
• Subjects:
  • Female
  • Humans
  • Breast Neoplasms
  • Pregnancy
  • Adult
  • Amino Acids
  • Pregnancy Trimester, Third
  • Prospective Studies
  • Middle Aged
  • Metabolome
• Keywords:
  • Amino acids
  • High-resolution metabolomics
  • Nutrient sensing
  • Pregnancy
• Source:
  Reproductive Toxicology (Elmsford, N.Y.), 2025, v. 133
• DOI:
  https://doi.org/10.1016/j.reprotox.2025.108866
• ISSN:
  0890-6238 ; 1873-1708
• Pubmed ID:
  40015485
• Pubmed Central ID:
  PMC11996058
• Document Type:
  Text
• Funding:
  HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; R01 ES031980/ES/NIEHS NIH HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; P30 ES019776/ES/NIEHS NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  108866 (21 pdf pages)
• Volume:
  133
• Download URL:
  https://stacks.cdc.gov/view/cdc/261645/cdc_261645_DS1.pdf
• File Type:
  [PDF - 1.01 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:e2f55dbff360c2680450569d34842b6425291440f4def5859acc93827f25fe27ca96d3d42db873d9302239b06529bc33023e065207151a5f92fac42b8b164b66