Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(2): 162-166

Research Article

10.5455/NJPPP.2025.v15.i2.8

Establishment of an age-specific reference range for serum total prostate-specific antigen levels among the Indian Bengali male population in a tertiary care hospital

Abhisek Das Choudhury¹, Pradipta Ghosh¹, Papia Sen² and Amrita Mukherjee¹*

¹Department of Biochemistry, R G Kar Medical College and Hospital, Kolkata, India²Department of Biochemistry, Medical College, Kolkata, India

*Corresponding Author: Amrita Mukherjee. Department of Biochemistry, R G Kar Medical College and Hospital, Kolkata, India. Email: dramritapublication [at] gmail.com

Submitted: 22/08/2024 Accepted: 03/01/2025 Published: 28/02/2025

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Abstract

Background: Globally, prostate cancer is the most prevalent malignant tumor associated with mortality in men. The most widely used tumor marker for prostate cancer diagnosis is the prostate-specific antigen (PSA). It is already known that racial and geographic factors influence blood PSA levels in various parts of the world. The main flaw of the currently utilized threshold of 4.0 ng/ml is that it underestimates the risk of cancer in younger men and causes unnecessary biopsies in older men. To the best of our knowledge, no reports have offered an age-specific reference range for serum total PSA levels in the male Bengali population of India.

Aim: Establishment of an age-specific reference range for serum total PSA levels among the Indian Bengali male population in a Tertiary Care Hospital.

Materials and Methods: A cross-sectional study was undertaken by R. G. Kar Medical College, including 822 healthy Indian Bengali males aged 30 years and above. The study population was divided into four age groups. After recording the general and clinical findings, serum total PSA was estimated using chemiluminescence immunoassay.

Results: In the age group (30–39) years the reference range is 0.02–1.9 ng/ml. In the 40–49 years age group and in the 50–59 years age group the reference ranges are 0.03–2.1 ng/ml and 0.03–2.8 ng/ml, respectively. The reference range obtained in the age group of >60 years was 0.14–3.8 ng/ml. Serum total PSA levels showed an increasing trend with increased age.

Conclusion: Age-specific reference range of serum total PSA showing a positive correlation with age was established among the Indian Bengali male population.

Keywords: Serum total PSA, Reference intervals, Age-specific PSA.

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Introduction

Prostate-specific antigen (PSA) is a serine protease of the kallikrein family that is exclusively produced by the epithelial cells of the acini and ducts of normal, hyperplastic, and cancerous prostatic tissues (Rifai 2023). The determination of PSA level is widely used for the diagnosis of prostatic carcinoma (Oesterling et al., 1995) the most common malignant tumor associated with mortality in men worldwide.

The most widely utilized tumor marker for prostate cancer diagnosis is the PSA. PSA is specific for prostatic tissue but not prostatic cancer. As people age, they also develop more benign prostatic hyperplasia (Lilja 2003; Malati and Kumari 2004; Casey and Conroy 2012; Bakir and Abo-Daher 2012; Rabah et al., 2019). It is well known that racial and geographic factors influence blood PSA levels in various parts of the world.

The accepted upper limit of serum PSA level is 4.0 ng/ml irrespective of age, race, and geographical location. The currently employed cutoff of 4.0 ng/ml has a clinical sensitivity of 78% (Rifai 2023) but unfortunately has the major fallacy of underestimating the risk of cancer in younger men and leads to unnecessary biopsies in men of older age groups (Lilja 2003).

To the best of our knowledge, there is no publication on the age-specific reference range of serum total PSA levels in the male Bengali population of India. To develop an age-specific reference range, we assessed serum PSA levels in Indian Bengali males of various age groups.

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Materials and Methods

Study design

The study was conducted in the department. Of Biochemistry after receiving approval from the West Bengal University of Health Sciences and The Institutional Ethics Committee. Kar Medical College and Hospitals, Kolkata, for a period of 18 months.

Study population

The sample size for this study was proposed according to the approved recommendation of the Expert Panel on the Theory of Reference Values of the International Federation of Clinical Chemistry. As recommended by the reviewers, a sample size of at least 120 reference values was taken (Burtis and Ashwood 1999). The study population was grouped into four categories. Therefore, we include in this study at least 480 Indian Bengali male subjects coming to the blood collection room of the Department of Biochemistry for routine medical examination at R.G. Kar Medical College and Hospitals, Kolkata. In this study, we enrolled 822 healthy Indian Bengali males without any prostatic disease and divided them into four groups.

Data collection

Five ml whole blood sample was collected from the phlebotomy room of the hospital. R.G. Biochemistry Kar Medical College and Hospital, Kolkata.

Blood was subjected to centrifugation at 3,000 rpm for 5 minutes, and serum was separated, and stored at −200C for further use.

Data analysis

PSA concentration is measured in nanograms per milliliter (ng/ml). All data were entered into Microsoft Excel 2013 and divided according to the age group of the decade: 30–39 years (Group-1); 40–49 years (Group-2), 50–59 years (Group-3), and above 60 years (Group-4). Finally, statistical analysis was performed using the SPSS Package, version 20 (IBM Corp., Armonk, NY, USA).

Total PSA was calculated for age in decades, including mean, median, and standard deviation. Quantitative data were evaluated for normal distribution using the Kolmogorov–Smirnov test. Differences in mean TPSA values across different age groups were done by the Kruskal–Wallis test as the data did not follow a normal Gaussian distribution. The 95% reference interval was estimated using the non-parametric method based on the 2.5th and 97.5th percentiles of PSA values obtained with a non-parametric estimation of the 90% confidence interval for percentiles. Spearman’s rank correlation coefficient was used to test the correlation of PSA as a function of age to determine the r value. All results were considered statistically significant when p < 0.05.

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Results

Patient demographics in Table 1 show the distribution of cases by age in 4 age groups with Group 1 (30–39 years), Group 2 (40–49 years), Group 3 (50–59 years), and Group 4 (≥60 years), comprised of 28.7%,31.9%,15.4%, and 23.8% of the sample population, respectively. It is observed in Table 2 that the mean difference in PSA was significantly (p < 0.05) increased across the 4 age groups.

Table 3 presents the comparative predicted 95% reference interval with 90% confidence interval (CI) of PSA across the 4 age categories. It was established that in age group (30–39) years, the reference range is 0.02–1.9 ng/ml. In the 40–49 years age group and in the 50–59 years age group the reference range are 0.03–2.1 ng/ml and 0.03–2.8 ng/ml, respectively, and the reference range obtained in age group ≥60 years is 0.14–3.8 ng/ml.

Figure 1 shows the distribution of serum PSA concentration as a function of age. The lower and upper ends of the whiskers indicate the minimum and maximum PSA ranges, respectively. The lower and upper ends of the boxes represent the 2.5th and 97.5th percentiles (95% reference interval). The intersection line represents the Median. It is observed in the scattered diagram (Fig. 2) that a statistically significant positive correlation was found between PSA and age.

Table 1. Distribution of cases by age in 4 age groups.

Table 2. Distribution of PSA levels according to age.

Table 3. Comparative predicted 95% reference interval with 90% CI of PSA across age categories.

Fig. 1. Serum concentration of PSA as a function of age. The lower and upper ends of the whiskers indicate the minimum and maximum PSA ranges, respectively. The lower and upper ends of the boxes represent the 2.5th and 97.5th percentiles (95% reference interval). The intersection line represents the Median.

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Discussion

PSA is a glycoprotein produced by the prostrate gland. Functionally, PSA is a serine protease of the kallikrein family exclusively produced by the epithelial cells of the acini and ducts of normal, hyperplastic, and cancerous prostatic tissues (Rifai 2023). The determination of PSA level is widely used for the diagnosis of prostatic carcinoma (Oesterling et al., 1995), the most common malignant tumor associated with mortality in men worldwide.

The early invasion of the basal cell layer by tumor cells causes a direct increase in PSA levels. PSA is a single-chain glycoprotein present in two forms in blood; Free PSA and Complexed PSA (Casey and Conroy 2012). Men with cancer have less circulating free PSA and more PSA bound to protein inhibitors (Rifai 2023). PSA levels can also increase in healthy men without any association with prostate cancer, such as prostatic hyperplasia (Malati and Kumari 2004). Serum PSA levels vary widely around the world. In comparison, European and Afro-American men have higher levels (Adel Bakir 2012; Rabah et al., 2019) than Asian men (Oesterling et al., 1995; Casey and Conroy 2012). The currently used cutoff of 4.0 ng/ml has a clinical sensitivity of 78% (Rifai 2023) but unfortunately has the major fallacy of underestimating the risk of cancer in younger men and leads to unnecessary biopsies in men of older age groups (Lilja 2003). Assessing blood PSA levels by age and population may help physicians screen for prostate cancer more successfully and assess tumor growth and response to treatment (Malati and Kumari 2004; Wu and Modlin 2012). Serum PSA levels are influenced by a number of factors, including race, ethnicity, and environmental factors, as well as changes in lifestyle, metabolism, and physiology as people age (Oesterling 1996; Thompson et al., 2004; Allan et al., 2011; Haythorn and Ablin 2011; Wu and Modlin 2012; Zhang et al., 2017). According to Asian-Indian research, the incidence of prostate cancer is increasing in urban areas (Malati and Kumari 2004; Gupta et al., 2015). The most common type of cancer in India is prostrate cancer, which ranks third in Delhi, fourth in Mumbai, fifth in Bangalore, and ninth in Chennai (Gupta et al., 2015).

Fig. 2. Scattered diagram showing the correlation between PSA and age.

As India is a socio-culturally and ethnically diverse country, there are significant differences in the prevalence of prostate disease. The causes of these discrepancies are not well understood. According to some studies, nutrition plays a significant role in these racial differences (Gupta et al., 2015). Research indicates that East Asian vegetarian diets are low in fat and contain curcumin or turmeric, which may have a preventive impact against the progression of prostate cancer (Gupta et al., 2015).

Age is one of the important prognostic factors with increment in age, and the likelihood of developing the disease too increases (Burtis and Ashwood 1999; Malati and Kumari 2004; Rifai 2023). Global comparisons of blood PSA reference values among healthy individuals from various populations revealed slight but notable differences. Numerous studies involving people from throughout the world, including Africans, Americans, Chinese, South Indians, Koreans, Singaporeans, and Japanese, have demonstrated that serum total PSA levels increase with age (Oesterling et al., 1995; Malati and Kumari 2004; Gupta et al., 2015).

Research on Japanese men and American white men revealed 95^th percentile, or top limit of the reference range of blood PSA, increased significantly with age (Oesterling et al., 1995; Oesterling 1996). According to a study by Malati and Kumari (Malati and Kumari 2004), the reference range of blood total PSA for healthy South Indian males is crucial for interpreting both benign and malignant prostate diseases. According to the study, the reference range of serum total PSA levels in South Indian males increases with age, although they are still lower than those of the general population worldwide.

In addition, previous research indicated that Indian men had lower serum levels of total PSA than people from other Asian nations (Gupta et al., 2015). Compared with other races, Asians have the lowest blood total PSA levels worldwide (Malati and Kumari 2004; Gupta et al., 2015). Because androgens are necessary for the prostate’s normal development and may promote its neoplastic transformation, low levels of androgen may explain the lower PSA levels (Gupta et al., 2015). According to the findings of several studies, ethnic variations exist in the PSA reference ranges, which should be considered when interpreting the results in clinical practice (Saw and Aw 2000; Matti and Zargar-Shoshtari 2021; Reza et al., 2021; Tsai et al., 2023).

The results of the present study suggest that the reference range of serum total PSA levels increases with advancing age in Indian Bengali men. In the age group (30–39) years the reference range is 0.02–1.9 ng/ml. In 40–49 years age group and in 50–59 years age group the reference range is 0.03–2.1 ng/ml and 0.03–2.8 ng/ml, respectively. The reference range obtained in the age group of >60 years was 0.14–3.8 ng/ml. The cutoff value established in our study was 4 ng/ml which is in concordance with the cutoff value suggested by the National Comprehensive Cancer Network (National Comprehensive Cancer Network, 2025).

Therefore, the regular application of age-specific reference intervals for serum total PSA will enhance the diagnostic efficacy in Indian Bengali male patients with prostate cancer and aid in the separation of those at high risk of developing very early prostate cancer.

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Conclusion

The serum PSA concentration increases with age, and the establishment of a reference range of age-specific PSA levels in Indian Bengali men could guide clinicians on the prevalence and incidence of prostrate cancer in this population with more specificity.

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Acknowledgments

The authors express their sincere gratitude to the Faculties, Laboratory Technicians, and all other staff members of the Department of Biochemistry, RG KAR Medical College and Hospital, Kolkata.

Conflict of interest

Nil.

Funding

Nil.

Author’s contributions

Concepts & Design: Amrita Mukherjee and Pradipta Ghosh. Literature search & Data acquisition: Abhisek Das Choudhury and Pradipta Ghosh. Statistical analysis: Papia SenManuscript preparation: Pradipta Ghosh and Abhisek Das Choudhury. Manuscript editing &review: Amrita Mukherjee and Papia Sen.

Data availability

https://osf.io/y7j5q/?view_only=b376d7f3731e49af9e10372d5cb82b01.

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