Gary Murray, Ph.D., Kathy Jung, Ph.D., Bill Dunty, Ph.D.

Replaces PA-17-220 and PA-17-219 Mechanisms of Alcohol-associated Cancers (Clinical Trial Not Allowed, R01/R21): Expiring September 8, 2020.

Purpose

This notice highlights interest in receiving investigator-initiated grant applications investigating the cellular and molecular mechanisms by which alcohol increases cancer risk. Epidemiological and biological research has established that chronic or excessive alcohol consumption increases the risk of at least seven different cancers, including mouth and oropharyngeal, laryngeal, esophageal, female breast, colorectal and liver cancer. Research is vital to gain a better understanding of the casual mechanisms by which alcohol increases cancer risk for certain tissues and organs. Further research is also needed to clarify dose-response relationships between alcohol and cancer risk, especially at low doses, and to better understand genetic and epigenetic variation in alcohol-induced carcinogenesis. These important mechanistic studies could lead to improved therapeutic approaches and preventative strategies and would provide guidance on safe levels of alcohol consumption.

Background

Alcohol is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Worldwide, 5.5% of newly diagnosed cancer cases and 5.8% of cancer deaths are attributable to alcohol use. Epidemiological and biological research has established that chronic or excessive alcohol consumption increases the risk of at least seven different cancers, including mouth and oropharyngeal, laryngeal, esophageal, female breast, colorectal, stomach, and liver cancer. Despite this long-standing body of work implicating alcohol in cancer risk, the specific causal mechanisms that result in the, initiation, promotion, progression or metastasis of tumors have not been characterized and the debate on the risks of low-level consumption persists.

Scope / Statement of Work

The objective of this NOSI is to highlight the interest of NIAAA and NCI in mechanistic research that will identify the causal links between the consumption of alcohol and the development of cancer, to clarify the dose-response relationships between alcohol and cancer risk, especially at low doses and the molecular, cellular, hormonal, immunological, and physiological factors that contribute to alcohol-induced cancer.

Outcomes / Justification

The focus of this NOFO is to encourage investigation into the mechanism(s) by which alcohol contributes to the development, initiation, promotion, progression or metastasis of cancer. As alcohol’s cancer-inducing properties are unique to certain organs, the tissue-specific factors that make each organ more susceptible to alcohol’s effects are of interest. Investigators are encouraged to employ physiologically relevant models of cancers that have been convincingly linked to alcohol consumption in humans, including cancers of the oral cavity and pharynx, esophagus, larynx, liver, breast, and colon and to investigate factors that contribute to alcohol-induced cancer including but not limited to the molecular, cellular, hormonal, immunological, and physiological changes induced by alcohol use.