Diet and Cancer (Poster Session)
Lawrence Mabasa, PhD (he/him/his)
Specialist Scientist
South African Medical Research Council
Cape Town, Western Cape, South Africa
Nasr Eshibona
South African Medical Research Council
Cape Town, South Africa
Anathi Burns
South African Medical Research Council
Cape Town, South Africa
Breast cancer is a leading cause of mortality and morbidity among women globally. Emerging evidence suggests that maternal nutrition during pregnancy significantly impacts offspring health, including cancer susceptibility, through epigenetic mechanisms like DNA methylation. Nutrients such as folate, choline, methionine, and vitamin B12 have been shown to reduce breast cancer risk in offspring, though the underlying mechanisms remain unclear. This study aimed to identify differentially expressed and methylated genes in mammary tumor tissues of female offspring and examine the influence of maternal methyl donor nutrients.
Methods:
Pregnant Sprague-Dawley rats were fed either a control diet or a micronutrient-supplemented diet during gestation and lactation. After weaning, female offspring were maintained on a control diet. At puberty, mammary cancer was chemically induced using DMBA. Tumor and normal mammary tissues were collected for analysis, and RNA sequencing was performed to identify differentially expressed genes.
Results:
A total of 46,729 transcripts were expressed across 18 samples, with 4,191 differentially expressed genes (DEGs) identified among the groups. Recursive Feature Elimination (RFE) analysis narrowed down 10 significant DEGs, including Tpst1, Gsc, Akr7a3, Trmt9b, Pik3c2g, Myl4, Acaca, Piezo1, AABR07059232.1, and H6pd. KEGG pathway analysis showed that these genes were enriched in pathways related to phosphatidylinositol signaling, cardiac muscle contraction, xenobiotic metabolism, fatty acid biosynthesis, TGF-beta signaling, and the pentose phosphate pathway.
Conclusions:
Among the identified genes, Pik3c2g plays a key role in cellular processes such as proliferation, transformation, survival, migration, and protein trafficking. Further studies are required to explore its epigenetic regulation and the impact of maternal methyl donor nutrients on fetal programming of breast cancer risk.
Funding Sources: National Research Foundation and The South African Medical Research Council