Impact of Diet and Obesity-Modulated Signaling in Breast Cancer: Causal Biology and Therapeutic Opportunities-Impact of Diet and Obesity-Modulated Signaling in Breast Cancer: Causal Biology and Therapeutic Opportunities

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In the first study, researchers examined the link between obesity, BRCA mutations, and breast cancer risk. They analyzed breast tissue from 72 individuals with BRCA mutations and found that higher BMI was associated with increased DNA damage in the breast tissue. Factors such as insulin, glucose levels, and insulin resistance markers were positively correlated with DNA damage, while markers of local inflammation did not show a significant association. Higher levels of SHBG, a protein that binds to hormones, were associated with lower levels of DNA damage. Cell models also showed that insulin stimulation could cause DNA damage in cells with BRCA mutations. Co-culture experiments with obese adipose tissue and breast tissue also demonstrated increased DNA damage. Gene expression analysis revealed differences in gene expression between lean and overweight/obese individuals with BRCA mutations. The findings suggest that obesity, insulin resistance, and hormonal factors may contribute to DNA damage and increased breast cancer risk in those with BRCA mutations.<br /><br />In the second presentation by Dr. Elizabeth Wahlberg, she discussed the impact of weight gain and FGF1 on estrogen receptor signaling in breast cancer. Dr. Wahlberg highlighted the association between obesity and postmenopausal breast cancer and suggested that metabolic health and weight gain may be more accurate predictors of cancer risk than BMI. She conducted research using mouse models and observed tumor growth during estrogen withdrawal in mice on high-fat or low-fat diets. Dr. Wahlberg explored the role of FGF1, a growth factor produced by fat cells, in tumor progression. She found that FGF1 levels increased in mammary adipose tissue during weight gain and correlated with weight gain rates and adipocyte size. Elevated levels of FGF1 receptor phosphorylation were associated with poor prognosis in ER-positive tumors. Dr. Wahlberg's research indicated that FGF1 may activate estrogen receptor signaling in the presence of obesity, leading to tumor growth. She suggested that the aggressive metabolic phenotype caused by FGF1 may contribute to this effect. Further investigation into the specific genes regulated by FGF1 and estrogen receptor signaling could provide more insights into this pathway. Overall, the study provides understanding into the complex relationship between obesity, FGF1, and estrogen receptor signaling in breast cancer.

Keywords

obesity

BRCA mutations

breast cancer risk

DNA damage

insulin

glucose levels

insulin resistance markers

local inflammation

SHBG

hormones

cell models

co-culture experiments


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