Alexa Weisbein

Introduction: Breast cancer is the most commonly diagnosed non-cutaneous cancer in women, and 1.7 million new cases are diagnosed yearly³. Breast cancer tumors are usually discovered by palpation, and staging can be done by biopsy.  Breast cancer has a variety of etiologies including genetic, lifestyle, hormonal and reproductive factors. It is estimated that diet contributes to 30-50% of breast cancer risks². It seems that high fat diet may contribute negatively to epigenetic regulation².  Questions that need to be answered by research include how a high fat diet during gestation can affect the mammary gland of the offspring, and how a high fat diet during gestation can increase the risk of mammary cancer through multiple generations. Methods: The study by Govindarajah et al. used female virgin Sprague-Dawley rats at 7 weeks of age, and used four randomized diets including a control, a high fat olive oil, high fat butter, and high fat safflower oil¹. The study by Vallacha et al. used one group of pregnant mice consuming a high fat n-6 polyunsaturated diet and a control group⁵.  Results: The study by Govindarajah et al. showed an 85.2% tumor incident in high fat diet groups. They stated that genes that repress transcription and are involved with cytosine methylation were downregulated in the high fat butter group¹. The study by Vallacha et al. showed a higher tumor incidence in both the F1 and F3 generations. The study also showed altered notch signaling, and an upregulation of ID4, which inhibits BRCA1 function⁵.  Conclusions: The study by Govindarajah et al. concluded that early epigenetic programming may be disrupted in mammary glands by looking at changes in methylation genes and pathways involved in breast development and homeostasis¹. The study by Vallacha et al. showed changes in ID4 can increase breast cancer mortality and frequency, and questioned if methylation patterns can affect more than one generation through avoiding the “loss of methylation markers” that normally occurs with each new generation⁵. By continuing to research the epigenetic effects of dietary fat, we can develop a better understanding of the high prevalence of breast cancer.

1. Govindarajah V, Leung Y-K, Ying J, et al. In utero exposure of rats to high-fat diets perturbs gene-expression profiles and cancer susceptibility of prepubertal mammary glands. The Journal of nutritional biochemistry. 2016;29:73-82. doi:10.1016/j.jnutbio.2015.11.003.
2. Yeung YK et al. Gestational high fat diet and bisphenol A exposure heightens mammary cancer risk. Endocrine Related Cancer. Jul;24(7):365-378. doi: 10.1530/ERC-17-0006.
3. Li C, Yang L, Zhang D, Jiang W. Systemic Review and meta-analysis suggest that dietary cholesterol intake increases risk of breast cancer. Nutr Res. 2016 Jul;36(7):627-35. doi: 10.1016/j.nutres.2016.04.009.
4. Nguyen NM, de Oliveira Andrade F, Jin L, et al. Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice. Breast Cancer Research : BCR. 2017;19:77. doi:10.1186/s13058-017-0866-x.
5. Vallacha A, Haider G, Kumar D. quality of breast cancer surgical pathology reports. Asian Pacific J Cancer Prevention. 2018 Mar 27;19(3):853-858. doI: 10.22034/APJCP/2018.19.3.853.