Single nucleotide polymorphism of fatty acid desaturase gene and breast cancer risk in estrogen receptor subtype

Gene. 2022 May 20:823:146330. doi: 10.1016/j.gene.2022.146330. Epub 2022 Feb 16.

Abstract

Background: Breast cancer (BC) is the most common cancer of women and the second most common cancer overall globally. Data suggest that the plasma concentration of omega fatty acids (n-3 and n-6) and the impact of the genetic variant are associated with diet-related inflammatory disease, BC. This study was aimed to find an association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and breast cancer estrogen receptor subtype.

Methodology: Hundred and two blood samples from women were quantified for fatty acids by gas chromatography. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing.

Results: The highest tertile of ALA showed a significantly reduced risk of BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1-1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and DPA was higher in GG genotype of ER-ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced risk of BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2-0.9).

Conclusion: The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu and that these pro-inflammatory effects might contribute to BC. We conclude that the individuals with genetically determined lower activity of FADS1(minor allele T) will derive greater advantage from n-3 FAs than those with higher FADS1 activity (G allele) and reduce the BC risk.

Keywords: Breast cancer; Estrogen receptor; FADS1; Omega-3 fatty acids; Omega-6 fatty acids; SNP rs174537.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adult
  • Arachidonic Acid / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Chromatography, Gas
  • Delta-5 Fatty Acid Desaturase / genetics*
  • Fatty Acids / blood*
  • Fatty Acids, Omega-3 / blood
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Estrogen / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • Delta-5 Fatty Acid Desaturase
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Receptors, Estrogen
  • Arachidonic Acid
  • FADS1 protein, human