Healthy lifestyle and prostate cancer risk in the Million Veteran Program

Abstract

Prostate cancer risk is understood to be mostly unchangeable and inherited. Currently, the strongest known risk factors for developing prostate cancer are age, race/ethnicity, family history and some specific genetic elements. The impact of healthy lifestyle on prostate cancer survivorship is a research priority because of potential impact on quality of life, progression of disease, and tolerance to treatment. Several studies have identified an association between tobacco use, low physical activity, and obesity with increased risk of prostate cancer progression and prostate cancer-related death. Additionally, environmental exposure to carcinogens is known to increase cancer risk including Agent Orange, a chemical agent used in the Vietnam War (1955-1975). Recent studies suggest a healthy lifestyle can mitigate a high inherited prostate cancer risk and risk of lethal prostate cancer, as shown in a combined analysis of two cohorts of health professionals. In this study, we utilize data from over 870,000 participants in the Million Veteran Program (MVP) to investigate the association of modifiable, environmental, and other factors on prostate cancer risk in a diverse population when accounting for the common major inherited risk factors: race/ethnicity, family history, and polygenic risk. The healthy lifestyle score (Range 0-4) is tabulated using answers to 60 questions in the MVP database for each participant, with a point assigned for each of the following: not a current smoker, healthy weight (body mass index [BMI] ≥ 30), strenuous activity >4 days per week, and a healthier than average diet. In this cohort, race/ethnicity, family history were associated with higher prostate cancer risks. When accounting for race/ethnicity and family history of prostate cancer, Agent Orange exposure was an independent factor for prostate cancer diagnosis (HR 1.06, 95% CI 1.04-1.09). Healthy lifestyle score was associated with a lower risk of metastatic prostate cancer (HR 0.80, 95% CI 0.77-0.82) and of fatal prostate cancer (HR 0.81, 95% CI 0.76-0.85) in the MVP cohort. Importantly, healthy lifestyle score was independently associated with reduced metastatic (HR 0.90, 95% CI 0.87-0.93) and fatal prostate cancer (HR 0.89, 95% CI 0.83-0.96) when accounting for race/ethnicity, family history, and genetic risk (PHS290). We report that environmental exposures are independently associated with prostate cancer risk when accounting for major inherited risk factors (family history, ancestry, and polygenic risk). Adherence to a healthy lifestyle is associated with lower risk of prostate cancer and with lower risk of dying from prostate cancer, which offsets high inherited risk.

Healthy dietary patterns and risk of prostate cancer in men at high genetic risk

“…Both our previous study in this cohort of health professionals 4 and another pre‐print study of military veterans in the United States 17 showed that among men with the highest genetic risk, adhering to a healthy lifestyle—defined by factors such as a healthy weight, vigorous physical activity and not smoking—was associated with lower risk of disease progression and death. The question of whether a healthy diet is associated with a lower risk remained unexplored.…”

“…We and others have shown that among men at high genetic risk, maintaining a healthy weight, being physically active, and not smoking can potentially lower the risk of aggressive prostate cancer 4,17 . Whether dietary patterns may lower prostate cancer risk among individuals at increased genetic susceptibility is currently unknown.…”

“…16 We and others have shown that among men at high genetic risk, maintaining a healthy weight, being physically active, and not smoking can potentially lower the risk of aggressive prostate cancer. 4,17 Whether dietary patterns may lower prostate cancer risk among individuals at increased genetic susceptibility is currently unknown. Therefore, within a large prospective cohort, we aimed to evaluate whether men at high genetic risk for prostate cancer, defined by a high PRS, can lower their risk of either overall or lethal prostate cancer by adhering to a healthy diet pattern.…”

Triglyceride-glucose index is a predictor of the risk of prostate cancer: a retrospective study based on a transprostatic aspiration biopsy population

“…Prostate cancer has become a common urological tumor in men, posing a serious risk to human health ( 1 – 12 ). Current factors that may influence prostate cancer are age, family history of tumors, genetic mutations, African ancestry, metabolic syndrome, and others ( 13 – 16 ). Metabolic syndrome is characterized by obesity, insulin resistance (IR), hypertension, and hyperlipidemia ( 17 ), and several current studies have demonstrated that insulin resistance is associated with prostate cancer, which can affect the development and progression of Pca through a variety of mechanisms, including the inflammatory pathway (Nuclear Factor Kappa B) (NF-κB) and cytokines, and increase the risk of developing prostate cancer ( 18 – 22 ).…”