Healthy lifestyle may offset risk of lethal prostate cancer in men with high genetic risk
Dr Anna Plym - Harvard University, Boston, USA
Thank you for your interest in our study, my name is Anna Plym, I am a postdoctoral fellow at the Brigham and Women’s Hospital. Our study is on the impact of lifestyle factors on the risk of prostate cancer in men at high genetic risk which we have presented at the AACR 2021.
The background for our study is that we know from previous studies that genetic factors are strong risk factors for prostate cancer and we have now identified more than 260 genetic markers for prostate cancer risk. When combined into a polygenic risk score these markers are incredibly good at identifying men at increased risk of prostate cancer. Among men at the highest genetic risk, that is men in the upper decile of this polygenic risk score, as many as 50% will be diagnosed with prostate cancer during their lifetime. When it comes to lifestyle factors we have now an increasing number of studies suggesting that a healthy lifestyle can reduce the risk of dying from prostate cancer. It may not protect against the overall risk of prostate cancer but I would say that for lethal prostate cancer the available evidence is quite convincing.
Given this potential benefit of a healthy lifestyle and the high burden of disease among men with a high polygenic risk score, we wanted to examine if men having a high genetic risk could reduce the risk of dying from prostate cancer.
For this study we used data from a large US cohort study of 50,000 male health professionals recruited in 1986 and around 10,000 of these men have been genotyped and could be included in the present analysis. All men filled out questionnaires regarding diet and lifestyle factors at multiple time points. Men were initially free from prostate cancer and they were followed for a diagnosis of prostate cancer or development of metastatic disease or death during a median follow-up period of twenty years.
To define genetic risk we used a 269 genetic variant polygenic risk score. This is the most recent polygenic risk score available for prostate cancer. It has been validated and found to highly predict prostate cancer risk with a tenfold difference in prostate cancer risk between men with a low and a high polygenic risk score.
To define a healthy lifestyle we used a healthy lifestyle score including six healthy lifestyle factors, that was healthy weight, not smoking, vigorous physical exercise three hours or more per week, and a high intake of tomatoes or tomato-based products and a high intake of fatty fish and a low intake of processed meat. We defined a healthy lifestyle as having at least four of these healthy behaviours.
We then examined the joint cancer risk of genetic risk and lifestyle risk score using time to event analysis, adjusting for several possible confounders such as PSA screening and medication use.
Our main novel finding is that among men who had the highest genetic risk, the most healthy lifestyle – the presence of four or more healthy lifestyle behaviours – reduced the risk of lethal disease by nearly 50%. This translates into a lifetime risk of lethal disease of 6% among the least healthy and 3% among the most healthy which is comparable to the population average. Also a moderately healthy lifestyle – the presence of three healthy behaviours – decreased the risk of lethal disease.
Adhering to a healthy lifestyle did not reduce the risk of overall prostate cancer across genetic risk groups which is in accordance with previous literature that has found that an unhealthy lifestyle is mainly a risk factor for more advanced disease.
I would also like to add while these results are encouraging we need to remember that our study was observational and we cannot rule out a possible influence of other factors that are associated with a healthy lifestyle. Ideally we would like to see a randomised trial of a lifestyle intervention in men at increased risk but it will be hard to do randomised experiments comparable to our study, both in terms of the lifestyle factors included – for example we cannot randomise men to smoke or not – and also the long follow-up required. Our findings are also preliminary at this point in time and we have not yet validated them in other populations.
Our findings suggest that a healthy lifestyle is of particular benefit among men at increased genetic risk and may offer a way for these men to decrease the risk of the consequences of prostate cancer, namely disease progression and death. If confirmed, our results can provide healthy guidance for these men. But we already know now and knowing about all of the other benefits of a healthy lifestyle we can recommend all men to adhere to a healthy lifestyle. With genetic testing being more widely used I think more people will be aware of their genetic risk and we need to be prepared with advice for people and men with increased risk, especially since genetic risk may be considered to be deterministic which our study and some other studies suggest it may not be.
We also need more research on how people will react to knowing about their increased genetic risk, can it increase motivation for a behavioural change? We will also need more research on the possible mechanisms behind our findings – what is it in the healthy lifestyle that reduced the risk of dying from prostate cancer? With a better understanding of these mechanisms it’s possible that we can use this information to come up with new ways to prevent or treat prostate cancer in the future.