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Session: Personalizing Nutrition - Genetics and Dietary Pattern interactions (Poster Theater Flash Session 2)

(PTFS02-03-23) Using genetics and metabolomics to assess the role of acetate in ischemic heart disease, diabetes, and sex hormone-related cancers: a Mendelian randomization study

Saturday, July 22, 2023
2:43 PM – 2:47 PM ET
Location:  Fairfax

    Presenting Author(s)

  • JZ

    Jie Zhao, PhD

    Assistant Professor
    University of Hong Kong
    Hong Kong, Hong Kong

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Disclosure(s):
Jie Zhao, n/a: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Acetate has attracted increasing attention with dual reputation, a potential benefit on cardiovascular health whilst a potential risk on cancer. Acetate may also affect sex hormones, possibly exerting a sex-specific effect and affecting sex hormone-related cancers.

Methods: Mendelian randomization was used to minimize confounding. We used genetic variants strongly (p < 5×10-8) and independently (r2 < 0.001) associated with acetate, as instrument. Then we obtained their overall and sex-specific associations with ischemic heart disease (IHD) (up to 154,373 cases), diabetes (109,731 cases), and several sex hormone-related cancers (prostate cancer, breast cancer, endometrial cancer, ovarian cancer and colorectal cancer, ranging from 8,679 to 122,977 cases), as well as with common risk factors (lipids, glycemic traits, blood pressure and body mass index) in large cohorts and consortia. Several methods, including penalized inverse variance weighted (pIVW), IVW, weighted median and weighed mode were used in the analysis.

Results: Genetically predicted acetate was associated with lower risk of IHD (odds ratio (OR) 0.61 per SD increase in acetate, 95% confidence interval (CI) 0.40 to 0.94) and lower triglycerides, with no sex disparity. Meanwhile, it was related to higher risk breast cancer (OR 1.28, 95% CI 1.10 to 1.49) and ER+ breast cancer (OR 1.33, 95% CI 1.11 to 1.60), robust to different methods.

Conclusions: Acetate may lower the risk of IHD but the benefit needs to be weighed against the potential risk on breast cancer. Factors affecting acetate activity, such as ACSS2, may be used as drug targets in the treatment for breast cancer.

Funding Sources: None