In a two-decade study conducted in JAMA network opened, The researchers analyzed the risk of early death from prostate cancer in men with higher compared to men with lower genetic risk, using data from two prospective cohort studies in Sweden and the United States of America (USA).
They found that men with a higher genetic risk had significantly higher early and late mortality rates from prostate cancer, although one-third of these early deaths could have been prevented by a healthy lifestyle.
Study: Early deaths from prostate cancer in men with higher vs. lower genetic riskImage credit: NTshutterth/Shutterstock.com
background
Despite advances in early diagnosis and treatment, prostate cancer remains one of the leading causes of cancer deaths in men, killing approximately 400,000 people worldwide each year. One third of these deaths occur before the age of 75, highlighting the need for new prevention approaches.
One promising approach is to target high-risk populations, including men with a high polygenic risk score (PRS). PRSs effectively classify prostate cancer risk and mortality. Combining the PRS with family history or measures of rare variants may improve risk assessment.
While known risk factors are not modifiable, lifestyle choices such as maintaining a healthy weight, not smoking, and getting regular physical activity may reduce the risk of developing and dying from prostate cancer, especially in high-risk individuals.
However, it remains unclear to what extent targeted prevention strategies can reduce the number of premature deaths from prostate cancer.
Therefore, in the present study, researchers analyzed data from two prospective cohort studies to assess the impact of genetic risk on early mortality and the effect of a healthy lifestyle on the prevention of prostate cancer.
About the study
Data from the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS) were analyzed.
The MDCS and HPFS included 10,270 and 9,337 genotyped men from Sweden and the United States, respectively, who did not have prostate cancer and had lifestyle data. The mean age at the start of follow-up was 59 years in the MDCS and 65.1 years in the HPFS.
A healthy lifestyle was defined using a score based on not smoking, high physical activity, a healthy body weight, and a diet rich in tomato products and fatty fish and low in processed meat.
This score categorizes the lifestyle as healthy (3–6 points) or unhealthy (0–2 points), with an additional detailed 4-group categorization and a sensitivity analysis taking into account various nutritional recommendations.
Genetic risk was classified as high or low using a multi-ancestry PRS of 400 variants for prostate cancer relative to a median value and family history of cancer.
Prostate cancer-specific deaths were tracked through the Swedish Death Cause Register (MDCS) and the National Death Index, supplemented by reports from next of kin.
Early deaths were defined as deaths before age 75, late deaths as deaths after age 75, and lifetime risk included deaths up to age 85. Statistical analysis included Cox regression, inverse probability-weighted models, and regression pooled by fixed-effects meta-analysis.
Results and discussion
According to the study, 67% of men were classified as being at increased genetic risk based on PRS and family history, and about 30% had a lifestyle score indicating unhealthy behavior.
During a mean follow-up period of 24 years in MDCS and 23 years in HPFS, 444 deaths from prostate cancer were recorded before (107) and after age 75 (337). Higher genetic risk was associated with a threefold increased rate of early and a twofold increased rate of late deaths from prostate cancer.
An unhealthy lifestyle significantly increased the risk only in men with a higher genetic risk, particularly in smokers and BMI ≥30. The results for the cohorts were consistent.
Men with lower genetic risk were found to have a lower lifetime risk of dying from prostate cancer, ranging from 0.6% to 1.3%, with no clear pattern by lifestyle. However, among men with higher genetic risk, the lifetime risk was significantly higher overall for men with higher genetic risk (2.3% to 3.1%).
For men in the PRS 50-75% category (1.8% to 2.9%), increasing further for men in the PRS 75-100% category (3.1% to 4.9%) in both studies. The majority of prostate cancer deaths occurred in men at higher genetic risk, accounting for 88% of deaths by age 75 years.
In men with an increased genetic risk, 22 to 36 percent of these deaths before age 75 could be prevented by changing their lifestyle. With alternative dietary factors, the probability is up to 39 percent.
The study is strengthened by the inclusion of two large, independent cohorts with 20 years of follow-up, showing consistent results across different populations. However, the analysis is limited by potential differences in prostate cancer testing and treatment, consideration of factors only at baseline, and inclusion of only men of European descent.
Diploma
In summary, this study should focus on men at high genetic risk for prostate cancer prevention.
About one-third of deaths from early-stage prostate cancer in men at genetic risk could be prevented by adopting a healthy lifestyle or by ensuring equal access to early detection and optimal treatment.
Targeted interventions in high-risk men could significantly reduce the number of premature deaths from prostate cancer.
