# ALCOHOL AND BREAST CANCER

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $341,552

## Abstract

Epidemiological and clinical studies indicate that alcohol abuse promotes the development of breast
cancer. There are two features of alcohol-induced tumor promotion: 1) alcohol consumption increases the risk
of breast cancer; 2) alcohol promotes cancer progression and is associated with more aggressive forms of
breast cancer. Therefore, alcohol exposure could affect both phases of mammary tumor development, namely,
tumorigenesis (cell transformation and onset of tumor) and cancer aggression (tumor growth, metastasis, and
drug resistance/recurrence). Adolescent alcohol drinking is a serious problem worldwide. The drinking age is
getting younger while the amount of alcohol uptake per occasion has increased. Adolescent
alcohol consumption is a risk factor for accidents, injuries, mental illnesses or some chronic diseases and
pathologies, as well as for the appearance of addictions, including alcoholism. Although the harmful effect of
adolescent alcohol exposure on the brain structures and behaviors, such as cognitive deficits and addiction
has been well studied, its effect on tumor risk has never explored. The molecular mechanisms underlying
alcohol tumor promotion, however, remain unclear. The adolescent is a critical period of mammary gland
development. Our study indicated that adolescent mice were more sensitive to alcohol tumor promoting effect
than adult mice. Our findings suggest that alcohol-induced tumorigenesis and progression/aggressiveness may
operate by different mechanisms. The p21 Activated Kinases (PAKs) are a family of serine threonine kinases;
PAK1 and PAK4 are particularly implicated in the carcinogenesis of mammary tumor. There are four members
of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38 and p38δ.
Although some of their physiological functions may overlap, the role of these MAPKs is quite different.
p38MAPK has been suggested to involve in the progression/aggressiveness of breast cancer. The central
hypothesis for this proposal is that alcohol-promoted mammary tumorigenesis and aggressiveness is mediated
by different mechanisms: alcohol-induced tumorigenesis is mainly mediated by PAK1/PDK4 and
estrogen/progestrone signaling pathway in the adolescents, while alcohol-induced aggressiveness mainly is
mediated by p38MAPK signaling pathway. We also hypothesize that the enhanced sensitivity of adolescent
to alcohol is due to that the signaling pathways regulating the development of mammary glands are more
sensitive to alcohol exposure. This proposal will test the hypothesis using both in vitro and in vivo approaches.
This proposal will for the first time investigate the impact of adolescent alcohol exposure on the development of
mammary glands and tumorigenesis/progression. It will not only elucidate the cellular and molecular
mechanisms underlying alcohol-mediated tumor promotion, but also help to develop therapeutic strategies for
treating alcohol promotion of breast cancer.

## Key facts

- **NIH application ID:** 10831968
- **Project number:** 5R01AA017226-17
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** JIA LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $341,552
- **Award type:** 5
- **Project period:** 2020-09-04 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831968

## Citation

> US National Institutes of Health, RePORTER application 10831968, ALCOHOL AND BREAST CANCER (5R01AA017226-17). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10831968. Licensed CC0.

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