Prostate cancer is the second most common cancer among men worldwide and the fifth leading cause of cancer-related death. In 2021, it is estimated that there will be 1.4 million new cases and 37,500 deaths caused by this disease1. Early detection of prostate cancer has become possible through the widespread screening of prostate-specific antigen (PSA) in middle-aged and older men, followed by biopsies over the last two decades2. PSA, also known as kallikrein-3, is a glycoprotein secreted by the prostate gland to liquefy serum, which promote sperm activity, and dissolve cervical mucus3, was first began to be used in the 1980s and 1990s to detect preclinical prostate cancer4.
There is no definitive conclusion on the normal value of PSA in serum, However, it is generally accepted that a serum PSA level below 4.0 ng/mL is normal. While cancer may be present below this value, and vice versa5. Further, PSA cannot distinguish between clinically significant cancers and those with low risk, leading to overdiagnosis, overtreatment and varying degrees of complications6. One of the main reasons for these issues is that PSA is not tumor-specific, and therefore, the clinical significance of its elevation can be caused by various factors, leading to ambiguity7,8.
Various factors, including age, obesity, diet, race, genetic variation, prostate volume, and non-malignant diseases, have been found to be associated with elevated PSA levels9. Several studies have investigated the correlation between these factors and PSA levels10–13. Among these factors, obesity has received more attention due to its high prevalence and severe chronic disease burden. Therefore, it is particularly important to clarify the relationship between obesity and PSA.
Many studies on obesity and prostate-specific antigen (PSA) levels have observed a tendency toward lower PSA concentrations as BMI increases, potentially hindering the detection of prostate cancer in obese individuals14,15. Nevertheless, conflicting findings exist, with some studies not confirming the inverse relationship. Instead, they have identified an association between BMI and total PSA mass, defined as the product of PSA concentration and plasma volume16, indicating a complex relationship.
Additionally, a majority of the existing studies rely on body indicators such as BMI and waist circumference to assess obesity, which, while clinically convenient, may lack technical accuracy. More precise methods, such as utilizing dual-energy X-ray absorptiometry (DXA) technology to measure fat content, could offer a better understanding of this relationship. Moreover, DXA technology provides insights into fat distribution, a clinically relevant factor that surpasses the significance of the total fat amount17.
In our study, we employed dual-energy X-ray absorptiometry (DXA) to precisely assess adiposity and fat distribution in the android and gynoid regions (TPF, APF, GPF). Our data were derived from a substantial and representative sample of the US general population, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2001 to 2010. The primary objective was to examine whether distinct associations between fat content and prostate-specific antigen (PSA) exist in different anatomical regions, akin to observations in the development of cardiovascular disease and diabetes18
Furthermore, we implemented age stratification to explore the relationship between adiposity and PSA concentration across different age groups.