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Gene & Protein in Disease                                      Testosterone as a biomarker of colorectal cancer




            Table 2. Hormonal frequency distribution of testosterone in colorectal cancer patients and controls based on their age
             Group   Particulars      Age range (years)  No. of subjects (n)  Testosterone (nmol/L)  t‑test/ANOVA  P‑value
            I       CTL              36 – 49 (42.62±6.10)  24            28.29±6.10        16.68      <0.0001*
                    CRC              37 – 49 (43.87±3.62)  24            6.40±2.03
            II      CTL              51 – 75 (61.08±6.32)  41            20.39±7.20       11.7546     0.0001*
                    CRC              51 – 78 (62.79±6.79)  41            6.58±2.18
            I       Dukes stage A (CRC)  38 – 48 (42.37±3.62)  8         7.43±1.86         1.35        0.26
            I       Dukes stage B (CRC)  37 – 49 (44.62±3.02)  14         6.0±2.31
            II      Dukes stage C (CRC)  48 – 71 (57.87±5.59)  25        6.92±2.54
            II      Dukes stage D (CRC)  57 – 78 (64.87±6.87)  18        5.85±2.42
            Notes: CRC: Colorectal cancer: CTL: Controls. Dukes Stages: A–D; Group I: Age<50; Group II: Age>50; Values are presented as mean±SD unless
            specified. *Statistically significant compared to controls (P<0.05).

            testosterone levels of Group  I at Dukes stage A and B   we observed significantly lower testosterone levels
            with the controls in Group  I, a statistically significant   (P < 0.05), which is consistent with findings from other
            difference was observed (P  < 0.0001). Similarly, when   investigations [25,26] . The testosterone levels in the CRC-
            comparing the differences between Group  II at Dukes   diagnosed  patients  in  this  study  aligned  with  those
            stages C and D and the controls in Group II, a significant   reported in other studies, both globally and across
            difference was also observed (P  < 0.0001). Interestingly,   age groups, reaffirming the validity of our results .
                                                                                                           [27]
            when  utilizing  ANOVA,  no  significant  difference  was   Furthermore,  several other studies have suggested that
            observed among different Dukes stages. This indicates   elevated testosterone levels in CRC patients at Dukes stages
            that all observed differences within the Dukes stages were   B and C may be indicative of more aggressive cancers [28-30] .
            negligible, as shown in Table 2. ANOVA is a justified and   Increased testosterone levels have been associated with
            widely accepted statistical method in scientific research   cancer progression and are used as a prognostic indicator
            due  to  its  ability  to  handle  multiple  groups,  control  for   for advanced CRC, with marker sensitivity increasing
            experiment-wise  error,  provide  valuable  insights  into   with tumor stages [31-33] . However, it is worth noting that a
            variability, and offer flexibility for various experimental   population-based study involving 3635 males revealed no
            designs. It helps researchers make informed decisions and   correlation between testosterone levels and the incidence of
            draw meaningful conclusions from their data, contributing   colon cancer, which contradicts the findings of our study .
                                                                                                           [34]
            to the advancement of scientific knowledge.
                                                                 Pregnenolone,   17-hydroxypregnenolone,  and
            4. Discussion                                      dehydroepiandrosterone are intermediates in one
                                                               of the pathways through which testosterone can be
            CRC is a complex illness influenced by various risk factors,   synthesized from cholesterol [5,35] . In males, the smooth
            including environmental exposure to chemicals, toxins,   endoplasmic reticulum of Leydig cells in the testes is
            and carcinogens, as well as endogenous factors. One   primarily  responsible  for  testosterone  production.  In
            such endogenous factor is reduced testosterone levels,   females, testosterone is primarily produced by the ovaries,
            which play a crucial role in controlling cell proliferation   suprarenal glands, and adipose tissue. In obese individuals,
            and apoptosis in healthy cells , as shown in Figure 3. As   testosterone is often converted to estradiol by the enzyme
                                   [21]
            testosterone levels decrease due to various factors, such as   aromatase. In addition, androstenedione and testosterone
            aging, alcohol consumption, and smoking, the risk of CRC   can undergo extra glandular aromatization to produce
            increases. However, there is limited knowledge regarding   estrone and estradiol, respectively . SHBG is a hepatically
                                                                                          [36]
            how testosterone affects cancer cells or the potential   produced glycoprotein that serves as the primary transport
            inhibitory effects of anti-androgens [22,23] . Recent research   protein for testosterone, playing a crucial role in regulating
            has proposed testosterone as a potential tumor biomarker   its bioactivity, as shown in  Figure  3. Altered levels of
            for CRC , alongside established tumor markers such as a   SHBG also contribute to CRC risk [19,37,38] . One important
                  [24]
            carcinoembryonic antigen.                          site where this regulation occurs is within the colon
              In the present study, when comparing the mean    epithelial cells. When the SHBG complex with testosterone
            testosterone levels among CRC participants who consume   reaches  these  cells,  testosterone is  released. Due  to  its
            alcohol and smoke to those in the control group who   lipophilic nature, it can easily pass through the cell
            were non-smokers, non-drinkers, and control groups,   membrane [12,39,40] . Once inside the cytoplasm, it binds to


            Volume 2 Issue 3 (2023)                         6                        https://doi.org/10.36922/gpd.1082
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