Dr. Anna Plym PhD Postdoctoral Research Fellow Brigham and Women's Hospital Harvard T.H. Chan School of Public Health

Prostate Cancer: Healthy Lifestyle Can Mitigate Risk of Lethal Disease In Men With Highest Genetic Risk

MedicalResearch.com Interview with:

Dr. Anna Plym PhD Postdoctoral Research Fellow Brigham and Women's Hospital Harvard T.H. Chan School of Public Health

Dr. Plym

Dr. Anna Plym PhD
Postdoctoral Research Fellow
Brigham and Women’s Hospital
Harvard T.H. Chan School of Public Health 

MedicalResearch.com: What is the background for this study? What are the main elements of the healthy lifestyle?

Response: Prostate cancer is the most heritable of all cancers, with genetic factors accounting for a large proportion of cases. Although we do not currently know about all the genetic factors contributing, a recent study identified 269 genetic markers for prostate cancer, validated in multiple independent populations (Conti et al., Nature Genetics 2021, Plym et al, JNCI, 2021: https://academic.oup.com/jnci/advance-article-abstract/doi/10.1093/jnci/djab058/6207974). Based on a polygenic risk score derived from these 269 markers, we observed that men with a high polygenic risk score have over a 50% risk of developing prostate cancer within their lifetime. With this excess risk in mind, we were interested in possible ways in which the genetic risk of prostate could be attenuated. An increasing number of studies have suggested that lifestyle factors can affect the risk of lethal prostate cancer – however, these studies have seldom incorporated genetic factors. We know from other diseases that a healthy lifestyle is of benefit for individuals at high genetic risk, and we hypothesized that this would be the case for prostate cancer as well. In this study, we examined a healthy lifestyle score for lethal prostate cancer consisting of six components: healthy weight (BMI < 30), not smoking (never smoked or quit > 10 years ago), vigorous physical exercise (3 or more hours per week), high intake of tomatoes or tomato-based products (7 servings or more per week), high intake of fatty fish (1 or more serving per week) and low intake of processed meat (less than 3 servings/week of beef or pork hot dogs, bacon, salami, bologna, or other processed meat sandwiches) (Kenfield et al, JCO, 2016). 

MedicalResearch.com: What are the main findings?

Response: We have three main findings.

  • First, we have confirmed that the latest available polygenic risk score can identify a large proportion of men at risk for prostate cancer. Men in the highest polygenic risk quartile had a 5-fold increased risk of prostate cancer compared to men in the lowest polygenic risk quartile, which translates into a lifetime risk of 55% versus 14%.
  • Second, we are the first to show that this polygenic risk score also can identify men at highest risk of dying from prostate cancer. However, this polygenic risk score is not specific for lethal disease, it also identifies men at risk for indolent disease.
  • Third, and perhaps most interesting, by combining the polygenic risk score with a healthy lifestyle score, we have been able to show that a healthy lifestyle can reduce the risk of lethal disease in men at highest genetic risk. This risk reduction was substantial, with close to a 50% reduced risk of lethal disease in men having the healthiest lifestyle (4-6 components of the healthy lifestyle score). We did not observe a similar reduction for overall prostate cancer, which is in line with previous observations of lifestyle factors mainly being associated with aggressive disease and progression. 

MedicalResearch.com: What should readers take away from your report? 

Response: Our findings suggest that men with at high genetic risk for prostate cancer may benefit from adapting a healthy lifestyle, including not smoking, a healthy weight, regular exercise, and a healthy diet. While this may not influence their risk of prostate cancer overall, it may help prevent disease progression and death. Not to forget, a healthy lifestyle have well-established benefits on multiple other diseases. I would however like to add that before specific guidelines for prostate cancer are implemented in clinical practice, our findings need to be validated within other populations. Also, since genetic testing of inherited variants is currently not standard of care, we need to study how well these findings translate to men with a family history of prostate cancer. We also need a better understanding of the underlying mechanisms; a healthy lifestyle correlates with many other factors that can influence prostate cancer progression and death.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Future research will need to prove that our findings are applicable also to other ethnic groups, other professions than health care professionals, and other countries. We also need further, preferable randomized studies, on the exact timing of a possible lifestyle intervention; does it have to be early in life or can it occur even after diagnosis?

MedicalResearch.com: Is there anything else you would like to add?

Response: While our findings are based on prospectively collected data within a large population of U.S. men with remarkable long follow-up, we cannot rule out the possible influence of confounding factors. A healthy lifestyle correlates with many other factors (such as PSA screening and better access to treatment), some of which it is not possible to fully control for in an observational study.

This study was funded by the DiNovi Family Foundation, the William Casey Foundation, the National Cancer Institute at the National Institutes of Health, the Swedish Society for Medical Research, and the Prostate Cancer Foundation.

We have no conflicts of interest. 


AACR 21 abstract
Can the genetic risk of prostate cancer be attenuated by a healthy lifestyle?

Anna PlymYiwen ZhangKonrad StopsackBénédicte DelcoigneAdam S. KibelEdward GiovannucciKathryn L. PenneyLorelei A. Mucci. Brigham and Women’s Hospital, Boston, MA, Harvard T. H. Chan School of Public Health, Boston, MA, Memorial Sloan Kettering Cancer Center, New York, NY, Karolinska Institutet, Stockholm, Sweden



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Last Updated on April 10, 2021 by Marie Benz MD FAAD