Abstract 192: Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood.

Abstract

Abstract Nutrition is thought to be involved in 30 to 50% of all breast cancer and intake of animal fat seems to be related to the increase of this type of cancer. It has been suggested that breast cancer can originate in early life, including the in utero and lactation periods. Maternal nutrition can modify the fetal environment and induce epigenetics modifications that change the susceptibility of offspring to breast cancer in adulthood. We hypothesized that exposure to high saturated fatty acid diet (HFS) in early life can change gene expression through the remodeling of epigenetic marks and consequently modify the risk of breast cancer. Sprague-Dawley rats were used in our study, which was composed of three groups: CO (female rats exposed to control diet [AIN-93G] in utero and lactation); PG (female rats exposed to HSF in utero) and PL (female rats exposed to HSF in utero and lactation). The distribution of fatty acid in the HSF was 37%, 38% and 24% of saturated, monounsaturated and polyunsaturated, respectively while in the CO diet, the distribution of those fatty acid was 17%, 27% and 55%, respectively. Female rats were euthanized on post-natal day (PND) 50 and blood and mammary tissue collected. Serum samples were assayed for estradiol, progesterone and leptin levels (radioimmunoassay and immunofluorescence). Mammary glands were evaluated for the number of terminal End Buds (TEBs), global DNA methylation (HPLC-DAD) and global histone modification patterns (western blot). Mammary tumor development induced by oral administration of dimethylbenz[a]anthracene (DMBA) on PND50 was also evaluated. Global DNA methylation were also determined in mammary tumors. There were no differences (P>0.05) in maternal caloric intake, offspring birth weight, serum estradiol levels or number of TEBs among the groups. Serum progesterone levels showed a tendency to increase (P=0.07) in the PG group compared to CO group. Compared to others groups, the PL group showed higher (P≤0.05) serum leptin levels. The PG group showed higher levels (P≤0.05) of global trimethylation of histone 3 lysine 9 (H3K9me3) compared to CO group, but no differences were observed (P>0.05) for global DNA methylation and global H3K9/H4K16 acetylation and H3K27/H3K4 trimethylation. The PG group showed lower incidence (P≤0.05) and average number of tumors compared to CO group and higher latency (P≤0.05) compared to PL group. The tumors from PG group presented lower (P≤0.05) global DNA methylation compared to others groups. In conclusion, exposure to HSF in early life influenced the susceptibility of breast cancer in adulthood. But, differently from what we expected the exposure to this diet in utero decreased breast cancer risk. If this exposure is continued through the period of lactation the protective effect is lost. This modification of breast cancer risk in early life seems to involve epigenetics mechanisms like post-translational histone modification. Citation Format: Fábia O. Andrade, Camile C. Fontelles, Mariana Rosim, Tiago F. Oliveira, Ana PM Loureiro, Marcelo M. Rogero, Fernando S. Moreno, Sonia M. De Assis, Leena Hilakivi-Clarke, Luis F. Barbisan, Thomas P. Ong. Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 192. doi:10.1158/1538-7445.AM2013-192