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

• Published in: Gene 2022-05, Vol.823, p.146330-146330, Article 146330
• Main Authors: Preethika, A., Sonkusare, Shipra, Suchetha Kumari, N.
• Format: Article
• Language: English
• Subjects: Adult; Arachidonic Acid - blood; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Chromatography, Gas; Delta-5 Fatty Acid Desaturase - genetics; Estrogen receptor; FADS1; Fatty Acids - blood; Fatty Acids, Omega-3 - blood; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Middle Aged; Omega-3 fatty acids; Omega-6 fatty acids; Polymorphism, Single Nucleotide; Receptors, Estrogen - genetics; Sequence Analysis, DNA; SNP rs174537; Young Adult
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146330

•Evidence shows that SNPs in the Fatty Acid Desaturase cluster affect fatty acid levels, which vary with breast cancer subtypes, race, and ethnicity.•Genetic variants specify the modification in the conversion of omega fatty acids catalyzed by desaturases and present study shows any documented negative influences of minor alleles of FADS1.•Future studies should move towards a clinical investigation into the efficacy and safety of n-3 FAs as a complementary therapy in all BC subtypes. 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. 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. 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). 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.