Alcohol and prostate cancer: identifying potentially modifiable lifestyle-related causes of cancer by means of Mendelian randomisation
Lead Research Organisation:
University of Bristol
Department Name: Social Medicine
Abstract
Alcohol has been linked to several cancers, but the picture is still unclear for prostate cancer. We aim to study the risk of prostate cancer in men with different alcohol intakes, as cutting down on alcohol might prevent this disease.
Prostate cancer is the most common cancer in men 50+ in the UK, and it is increasing as we live longer.
Even if we anticipate that the effect of alcohol might be small, we are interested in finding out more because alcohol consumption and prostate cancer are both on the rise, affecting many of us, and drinking behaviours could be targeted and modified.
Alcohol is difficult to study because we forget how much we have drunk over the years, and because heavy drinkers also tend to smoke and be generally less healthy.
Instead of asking men directly, we will try to classify heavy/moderate/light drinkers, based on some of their genes that are believed to influence their drinking or affect the way their body gets rid of alcohol. Comparing men with and without prostate cancer will reveal what link there is with alcohol.
Prostate cancer is the most common cancer in men 50+ in the UK, and it is increasing as we live longer.
Even if we anticipate that the effect of alcohol might be small, we are interested in finding out more because alcohol consumption and prostate cancer are both on the rise, affecting many of us, and drinking behaviours could be targeted and modified.
Alcohol is difficult to study because we forget how much we have drunk over the years, and because heavy drinkers also tend to smoke and be generally less healthy.
Instead of asking men directly, we will try to classify heavy/moderate/light drinkers, based on some of their genes that are believed to influence their drinking or affect the way their body gets rid of alcohol. Comparing men with and without prostate cancer will reveal what link there is with alcohol.
Technical Summary
Aims
To use classic epidemiological and Mendelian randomisation approaches to establish whether alcohol is causally related to cancer at various sites, with particular emphasis on prostate cancer.
Objectives
1. To systematically review the evidence on alcohol, alcohol-metabolising genotypes, and cancer risk
2. using bioinformatic approaches, to identify a set of polymorphisms in European-origin populations, related to alcohol intake and metabolism
3. to investigate the association between prostate cancer risk and the above polymorphisms.
Design
Alcohol is thought to be one of the main avoidable causes of cancer, however the evidence for its actual causal influence for some sites is inconclusive. The main limitations of observational studies for examining these associations are bias, confounding and measurement error. The association between a disease and a polymorphism that influences exposure is not susceptible to these problems. If an exposure is truly a causal factor for disease, a polymorphism should be associated with the disease to the extent that it modifies the exposure of interest. This approach will be used to determine the role of alcohol intake for cancer risk using existing data from case-control studies of alcohol metabolising genotypes via systematic reviews. In addition, we will generate new data, by applying this technique (using established and emerging polymorphisms) to a large population-based study of screen-detected prostate cancer.
Methodology
The medical and scientific literature will be searched for association studies of alcohol metabolising genes and cancer risk. A systematic review and a meta-analysis (where sufficient studies are found) will be performed for each cancer site. Using bioinformatics, a set of genetic variants will be identified, which are involved in influencing alcohol intake or metabolism and are present at frequencies of at least 5% in Caucasian populations. The focus will be on identifying variants with some evidence of functionality or of being in linkage disequilibrium with functional variants. These variants will then be investigated in a large nested case-control study of prostate cancer (N cases=3000).
Scientitic and Medical opportunities of the study
Associations between polymorphisms related to alcohol intake and cancer risk will allow inference to be made on whether alcohol is causally related to cancer at various sites, in particular prostate cancer. Findings will therefore contribute to evidence-based recommendations on cancer prevention. In addition, skills acquired during this fellowship will equip me to answer a variety of research questions relating to whether avoidable exposures are risk factors for disease, integrating genetic and observational epidemiology approaches.
To use classic epidemiological and Mendelian randomisation approaches to establish whether alcohol is causally related to cancer at various sites, with particular emphasis on prostate cancer.
Objectives
1. To systematically review the evidence on alcohol, alcohol-metabolising genotypes, and cancer risk
2. using bioinformatic approaches, to identify a set of polymorphisms in European-origin populations, related to alcohol intake and metabolism
3. to investigate the association between prostate cancer risk and the above polymorphisms.
Design
Alcohol is thought to be one of the main avoidable causes of cancer, however the evidence for its actual causal influence for some sites is inconclusive. The main limitations of observational studies for examining these associations are bias, confounding and measurement error. The association between a disease and a polymorphism that influences exposure is not susceptible to these problems. If an exposure is truly a causal factor for disease, a polymorphism should be associated with the disease to the extent that it modifies the exposure of interest. This approach will be used to determine the role of alcohol intake for cancer risk using existing data from case-control studies of alcohol metabolising genotypes via systematic reviews. In addition, we will generate new data, by applying this technique (using established and emerging polymorphisms) to a large population-based study of screen-detected prostate cancer.
Methodology
The medical and scientific literature will be searched for association studies of alcohol metabolising genes and cancer risk. A systematic review and a meta-analysis (where sufficient studies are found) will be performed for each cancer site. Using bioinformatics, a set of genetic variants will be identified, which are involved in influencing alcohol intake or metabolism and are present at frequencies of at least 5% in Caucasian populations. The focus will be on identifying variants with some evidence of functionality or of being in linkage disequilibrium with functional variants. These variants will then be investigated in a large nested case-control study of prostate cancer (N cases=3000).
Scientitic and Medical opportunities of the study
Associations between polymorphisms related to alcohol intake and cancer risk will allow inference to be made on whether alcohol is causally related to cancer at various sites, in particular prostate cancer. Findings will therefore contribute to evidence-based recommendations on cancer prevention. In addition, skills acquired during this fellowship will equip me to answer a variety of research questions relating to whether avoidable exposures are risk factors for disease, integrating genetic and observational epidemiology approaches.