AACR, Author Interviews, Brigham & Women's - Harvard, Cancer Research, Nutrition, Prostate Cancer / 10.04.2021
Prostate Cancer: Healthy Lifestyle Can Mitigate Risk of Lethal Disease In Men With Highest Genetic Risk
MedicalResearch.com Interview with:
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Dr. Plym[/caption]
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).
Dr. Plym[/caption]
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).
Catharina Svanborg M.D., Ph.D.
Professor at Lund University Department of Laboratory Medicine,
Division of Microbiology, Immunology and Glycobiology
Founder/Chairman of the Board at HAMLET Pharma
MedicalResearch.com: What is the background for this study?
Like many unexpected scientific developments, this finding was serendipitous. In our search for the molecular basis of host susceptibility to infection, we discovered that infection directly affects MYC levels.
Gene expression analysis revealed that MYC itself was inhibited and that genes regulated by MYC were affected in children with acute kidney infection. Rapid reductions in MYC levels was further confirmed by infecting human kidney cells with the pathogenic E. coli bacteria isolated from patients with acute pyelonephritis, allowing us to formulate the hypothesis that bacteria regulate host MYC levels during acute infection and to investigate the mechanism leading to this inhibition. This work was conducted by the
Dr. Lara-Corrales[/caption]
Irene Lara-Corrales, MD
Associate Professor of Pediatrics at the University of Toronto
Staff physician in Pediatric Dermatology at the
Hospital for Sick Children in Toronto, Canada
She is a member of the
Dr. Gerstung[/caption]
Moritz Gerstung PhD
Group Leader: Computational cancer biology
EMBL-European Bioinformatics Institute
MedicalResearch.com: What is the background for this study?
Response: We have learned a lot in the last ten years about the molecular nature about various cancers thanks to the resources created by TCGA, ICGC and many other initiatives. Similarly, digital pathology has progressed hugely due to new AI algorithms. Yet it hasn’t been explored deeply how a cancer’s genetic makeup and its histopathological appearance are related. Here computers can be very helpful as they can process large amounts of digital microscopy slide images and test whether there are any recurrent histopathological patterns in relation to hundreds or thousands of genetic and other molecular abnormalities.