Figure 1) of the testosterone, FSH, and LH indicates positive test (0.670, 0.726 and 0.775). Conclusions: Changes in the levels of steroid hormones and lipids could correlate with the elevated chance of CRC. Therefore, assessment of multiple markers might overcome and provide better judgment in patients with CRC."/> Figure 1) of the testosterone, FSH, and LH indicates positive test (0.670, 0.726 and 0.775). Conclusions: Changes in the levels of steroid hormones and lipids could correlate with the elevated chance of CRC. Therefore, assessment of multiple markers might overcome and provide better judgment in patients with CRC."/>

Serum Lipid Profile and Steroid Hormone Levels in Patients with Colorectal Cancer

AUTHORS

Roya Abbasi Natajomrani 1 , Durdi Qujeq ORCID 2 , * , Reza Hajihosseini 1 , Vahid Hosseini 3

1 Department of Biochemistry, Payame Noor University, Tehran, Iran

2 Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran

3 Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran

How to Cite: Abbasi Natajomrani R , Qujeq D, Hajihosseini R , Hosseini V . Serum Lipid Profile and Steroid Hormone Levels in Patients with Colorectal Cancer, Hormozgan Med J. Online ahead of Print ; In Press(In Press):e102085. doi: 10.5812/hmj.102085.

ARTICLE INFORMATION

Hormozgan Medical Journal: In Press (In Press); e102085
Published Online: November 10, 2020
Article Type: Research Article
Received: April 12, 2020
Revised: July 28, 2020
Accepted: August 3, 2020
Uncorrected Proof scheduled for 25 (1)
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Abstract

Background: Lipids are usually crucial to develop tumors, and dyslipidemia is correlated with the high chance of colon and colorectal cancer (CRC). Steroid hormones such as estrogen and progesterone can decrease the risk of colorectal cancer development.

Objectives: The present study aimed to compare the serum levels of lipid profile and steroid hormones in patients with CRC and healthy controls.

Methods: The present study included 40 consecutive adult patients with CRC in the Mazandaran Cancer Center, Sari, Iran, between 2017 and 2020.The diagnosis of CRC was evaluated based on colonoscopy with biopsy and CT scan. Also, the diagnosis of CRC was based on NCCN clinical practice guidelines in oncology. Blood samples were taken before treatment during routine testing. A 5 mL of peripheral blood was collected from each patient. All patients signed the written consent for the study. Also, a total of 40 healthy subjects were selected as healthy controls from the same area during a routine physical examination, which was also confirmed by screening colonoscopy and pathology. Serum TCh and TG levels were quantitatively determined by the colorimetric method. LDL-C and HDL-C were determined by the turbidimetric immunoassay. Steroid hormones were quantitatively determined by the Enzyme-linked immunosorbent assay (ELISA) according to the reagent manufacturer’s instruction. To analyze data, the SPSS software package (version 21) was applied.

Results: Among all the indicators studied, the (mean ± SD) of testosterone, FSH and LH levels was higher (1.85 ± 1.63 ng/ml, 15.35 ± 0.13mIU/l, 12.42 ± 0.12.16mIU/ml) in patients with CRC than (mean ± SD) healthy controls (0.40 ± 0.21ng/ml, 6.27 ± 0.50mIU/ml, 2.89 ± 0.20mIU/ml, P < 0.05), respectively. Also, the results in subgroups showed that the mean testosterone (0.91 ± 1.2ng/l), FSH (19.11 ± 16mIU/ml), LH (14.49 ± 14mIU/ml) levels in the woman patients with CRC was higher than healthy female controls and had more statistical significance (p = 0.02, 0.00, 0.00), respectively. The area under the AUC cure (Figure 1) of the testosterone, FSH, and LH indicates positive test (0.670, 0.726 and 0.775).

Conclusions: Changes in the levels of steroid hormones and lipids could correlate with the elevated chance of CRC. Therefore, assessment of multiple markers might overcome and provide better judgment in patients with CRC.

1. Background

Colorectal cancer (CRC) is a common malignancy with poor prognosis and survival rates. It is one of the leading causes of cancer-related deaths worldwide. CRC has originated from the epithelial cells lining the colon or rectum of the gastrointestinal tract. Symptoms of CRC include blood in the stool, change in bowel movements, weight loss, and feeling tired. It might be caused by old age, lifestyle, and genetic disorders. CRC was diagnosed by the sampling of areas of the colon suspicious for possible tumor development. The third most common cancer in the world is colorectal cancer leading to death (1). CRC is the most common cancer in Iranian women and men and ranks third in Iranian men and fourth in women. (2). In this regard, lipoproteins are vital in cancer progression by providing lipids for malignant cells and tumors (3). Although several studies have been conducted on the relationship between serum lipids, plasma lipoproteins, and cancers, there is little research on the association between blood lipids profile, colon, and colorectal cancer (4, 5). Changes in serum cholesterol levels in the CRC diagnosis process have been observed (6). On the other hand, the levels of TCh and LDL-C and the LDL-C/HDL-Ch ratio were significantly higher in patients with CRC than controls (7). Furthermore, dyslipidemia was correlated with the elevated chance of colon and colorectal cancer, but the results regarding the increase, decrease or inactivity of fats are inconsistent and still controversial. Also, the role of steroid hormones, especially testosterone, has increased the risk of colorectal cancer (8). Epidemiological studies have shown that an increase in female sex hormones such as estrogen and progesterone can decrease the risk of colorectal cancer development. On the other hand, women are less likely to have colorectal cancer than men due to the protection role of the estrogens (9). Studies have interestingly shown that testosterone hormone has a stronger effect in developing colorectal cancer than the protecting effect of estrogen hormone. Also, after the decrease of testosterone, the rate of incidence of colorectal cancer can be decreased (10). Estrogen supplementation in postmenopausal females can enhance HDL-Ch (11). Also, it reduces the total and LDL-Ch concentration in women (12). According to the researchers, estrogen provokes the LDL-Ch degradation and decreases the assembled LDL particles oxidation in the endothelium (13). Besides, the hormones, lipids, the expression of genes, proteins, and some biomarkers released by tumors suggested as vital to develop some cancers, and they may play a role in the detection of cancers (14-18). Therefore, the assessment of multiple markers might overcome and provide better judgment in patients with CRC. In this regard, this research aimed to investigate the altered serum levels of lipid profile and steroid hormones in patients with CRC. Also, to investigate the hypothesis that serum levels of lipid profile and steroid hormones may affect the CRC patients.

2. Objectives

The objective of this study was to compare the serum levels of lipid profile and steroid hormones in patients with CRC and healthy controls.

3. Methods

A total of 40 CRC patients were consecutively recruited from the hospitalized in the Imam Khomeini Educational Hospital and Tuba Clinic, Mazandaran University of Medical Sciences, in Sari between January 2017 and April 2020. The patients were within the age range of 30 to 70 years (20 males and 20 females). The diagnosis of CRC was based on NCCN clinical practice guidelines in oncology (19). The patients had no medications before the sample collection. Having consulted with a gastroenterologist, we verified the diagnosis of the patients. All patients with biopsy-proven CRC were included in the study. Also, the International Classification of Diseases was used to identify patients with a diagnosis of CRC, and diagnoses were verified from a registry kept by the pathology department. Demographic data, including name, age, gender, and race, were collected. Also, a total of 40 (8 males and 32 females), aged 30 – 70 years subjects, were selected as healthy controls from the same area during a routine physical examination, which was also confirmed by screening colonoscopy and pathology. The control group was healthy volunteers who were not taking medicine or any form of hormonal medication. Also, control subjects were selected free of cancer at the time of diagnosis of the matching case and were matched to cases by study center, sex, age time of blood collection, and fasting status. Venous blood samples were collected after an overnight fast from the patients. The blood was allowed to clot, centrifuged at 3000 rpm for 10 min, and serum was collected and stored at -80oC until assayed. We collected the written informed consent before collecting samples from all patients as well as healthy controls. The study protocol was approved by the Ethics Committee of the Payame Noor University (IR.PNU.REC.1397.036). Written informed consent was obtained from all participants before enrollment.

3.1. Measurements

Serum TCh and TG levels were quantitatively determined by the colorimetric method called a Roche Mindray- BS-800 Automatic Biochemistry Analyzer. LDL-C and HDL-C were determined by the turbidimetric immunoassay (20). Steroid hormones were quantitatively determined by the Enzyme-linked immunosorbent assay (ELISA) according to the reagent manufacturer’s instruction. The selection criteria were patients with a confirmed diagnosis of CRC who were 3 - 70 years of either both sex and who resided in the Mazandaran. Participants were selected based on the information obtained by clinical records. (Testosterone Elisa Kit (Ideal Tashkhis Atieh- cat.NO: 2424-96). Estradiol E2 Elisa Kit (Ideal Tashkhis Atieh- cat.NO: 2824-96). DHEA-S Elisa Kit (Ideal Tashkhis Atieh- cat.NO: 2624-96). FSH Elisa Kit (Ideal Tashkhis Atieh-H03LIG8). LH Elisa Kit (Ideal Tashkhis Atieh-H02LIH8). TRIGLYCERIDES diagnostic Kit (GPO-PAP)-pars azmun. CHOLESTEROL diagnostic Kit - (CHOD) - pars azmun. LDL-C- diagnostic Kit – pars azmun. HDL-C- diagnostic Kit -pars azmun.

3.2. Inclusion Criteria

Patients aged 30 to 70 years, CRC patients who were diagnosed by consultation with a gastroenterologist, no experience of chemotherapy and radiotherapy treatment, patients with rectal bleeding and a change of bowel habits, patients with a palpable rectal mass, patients iron deficiency anemia, and control subjects were selected free of cancer.

3.3. Exclusion Criteria

Age above 70 years or under 30 years, undergoing chemotherapy and radiotherapy, smoking cigarettes, having a history of other cancers and malignant and autoimmune disease, taking medicine or any form of hormonal medication, and some drugs that interfere with lipid metabolism.

3.4. Statistical Analysis

We used the SPSS software package (version 21) to analyze the data. The results were expressed as means ± standard deviations (mean ± SD). We also used t-tests to compare the colorectal cancer patients and control groups in terms of the lipid profile and steroid hormone levels. A p-value < 0.05 for the variable difference between groups was set to be significant statistically. The receiver operating characteristic (ROC) was conducted for testosterone, FSH, and LH. Pearson rank correlations were used to run the correlation analysis between quantitative variables.

4. Results

Table 1 summarizes the demographics of all subjects enrolled in the study. In brief, patients with CRC (n = 40, 20 women and20 men) and 40 healthy controls (32 women and 8 men). The mean age of patients with CRC was 60 ± 9.42 years (range 30 – 70 years); eligible patients had histologically or pathological tests. The mean age of healthy controls was 43 ± 13.4 years (range 30 – 70 years). Serum steroid hormones and lipid profile levels in patients with CRC and healthy controls are shown in Tables 2 and 3, respectively. The (mean ± SD) of testosterone, FSH, and LH levels (1.85 ± 1.63 ng/ml, 15.35 ± 0.13 mIU/l, 12.42 ± 0.12.16 mIU/ml) were higher in patients with CRC, than (mean ± SD) the healthy controls (0.40 ± 0.21 ng/ml, 6.27 ± 0.50 mIU/ml, 2.89 ± 0.20 mIU/ml, P < 0.05)and had statistical significance (P < 0.05) (Table 2).Also, the results in sub-groups showed that the mean testosterone (0.91 ± 1.2ng/l), FSH (19.11 ± 16mIU/ml) , LH (14.49 ± 14 mIU/ml) levels in the woman patients with CRC was higher than healthy controls and had more statistical significance (P = 0.02, 0.00, 0.00), respectively .The area under the AUC cure (Figure 1) of the testosterone, FSH, and LH indicates a positive test (0.670, 0.726, and 0.775), respectively. Table 4 shows the relationship between hormones and lipids levels in patients with CRC.

Table 1. Demographic Features of CRC Patients and Healthy Controls
VariableControl GroupCancer GroupP Valuea
Number4040
Gender0.005
Female3220
Male820
Age, year (mean ± SD)43 ± 13.460 ± 9.420.059
Weight(kg) (mean ± SD)69.38 ± 8.1673.32 ± 11.630.048
BMI (kg/m2) (mean ± SD)25.61 ± 2.3127.22 ± 4.30.001

aP values for case-control comparisons from Chi-square, T-test.

Table 2. Mean Values of the Studied Steroid Hormone Levels in CRC Patients and Control Group
VariablesTotal (Men, Woman)MenWoman
No.Mean ± SDP ValuesaNo.Mean ± SDP ValuesaNo.Mean ± SDP Valuesa
Testosteroneone0.000.230.02
CRC381.48 ± 1.63192.05 ± 1.81190.91 ± 1.2
CONTROL330.40 ± 0.2120.46 ± 0.11310.40 ± 0.21
DHEA0.640.050.56
CRC370.75 ± 0.49200.66 ± 0.54170.86 ± 0.41
CONTROL390.83 ± 0.7981.15 ± 0.66310.74 ± 0.81
Estradiol0.280.780.31
CRC3741.73 ± 0.212043.45 ± 171739.71 ± 0.25
CONTROL3648.55 ± 0.31845.74 ± 242849.36 ± 0.33
FSH0.000.380.00
CRC3715.35 ± 0.132012.15 ± 91719.11 ± 16
CONTROL356.27 ± 0.5088.92 ± 4275.48 ± 6
LH0.000.060.00
CRC3912.42 ± 0.122010.46 ± 11.011914.49 ± 14
CONTROL342.89 ± 0.2082.01 ± 1.72262.89 ± 2.5

aP values for case-control comparisons from T-test.

Table 3. Mean Values of the Studied Lipid Profile Levels in CRC Patients and Control Group
VariablesTotal (Men, Woman)MenWoman
No.Mean ± SDP ValuesaNo.Mean ± SDP ValuesaNo.Mean ± SDP Valuesa
TCh0.9340.4900.811
CRC39179.79 ± 5319180.52 ± 5120179.1 ± 56
Control38178.89 ± 408165.87 ± 4430182.3 ± 39
TG0.5840.8650.037
CRC37153.13 ± 17718181.44 ± 25319126.3 ± 26
Control38170.68 ± 848165.62 ± 6130172.03 ± 90
LDL0.5660.5320.704
CRC40108.55 ± 3920107.75 ± 3920109.35 ± 40
Control39104.10 ± 27897.75 ± 3231105.74 ± 26
HDL0.179.0570.734
CRC4045.72 ± 142047.18 ± 1502044.27 ± 13
Control3941.15 ± 15.834.78 ± 133142.80 ± 15

aP values for case-control comparisons from T-test.

Figure 1. Analysis of testosterone, FSH, and LH of sensitivity and specificity in the diagnosis of colorectal cancer by ROC curve. Data from the spectrophotometric method for FSH and LH (Considering the larger test result indicates more positive test). ROC curve analysis shows Area under Receiver Operating Characteristic (AUROC) 0.670, 0.726, and 0.775. (AUROC) > 0.9; high accuracy, (AUROC) = (0.7 - 0.9); moderate accuracy, (AUROC) = (0.5 - 0.7); low accuracy.
Table 4. Relationship Between Hormone Levels and Lipid Levels in Patients with CRC (Pearson Correlation)
VariableTestosteroneDHEAEstradiolFSHLH
TCh
Pearson Correlation0.083-0.063-0.1150.217-0.042
Sig. (2-tailed)0.5000.5990.3430.0720.726
No.6973707071
TG
Pearson Correlation0.034-0.026-0.003-0.042-0.102
Sig. (2-tailed)0.7830.8270.9780.7370.410
No.6771686768
LDL
Pearson Correlation0.072-0.049-0.0840.1900.014
Sig. (2-tailed)0.5510.6790.4860.1100.909
No.7075727273
HDL
Pearson Correlation0.1680.002-0.0980.156-0.009
Sig. (2-tailed)0.1650.9870.4140.1910.942
No.7075727273

5. Discussion

According to this study, the levels of FSH, LH, DHEA, and testosterone in female patients with CRC were significantly increased when compared to healthy controls. However, their level of estradiol was decreased. Also, male patients with CRC showed a statistically significant increase in the levels of FSH, LH, and estradiol, although, unlike healthy control, their level of DHEA and testosterone was decreased. The present study also showed that the level of TG in female patients with CRC, unlike healthy control, was decreased. In male patients with CRC, there was an increase in the level of TCh, HDl-Ch, and LDL-Ch, compared to healthy control. These results showed the importance of lipid and lipoproteins in CRC, which is in line with the fact that lipids are usually crucial to develop tumors, and lipoproteins have shown critical for cancer progression (3). The results also showed the association between lipids profile and colon and colorectal cancer rates (4, 5). Moreover, reductions in serum cholesterol levels were observed in patients with CRC (6). It was reported that the levels of TCh and LDL-Ch and the LDL-Ch/HDL-Ch were significantly higher in patients with CRC than healthy controls (7). Also, the role of steroid hormones, such as testosterone, was to increase the risk of colorectal cancer (8). Increasing female sex hormones such as estrogen and progesterone can decrease the risk of colorectal cancer development due to the protection roles of these hormones (9). Besides, our results showed that testosterone and DHEA level are high in CRC female patients, but the estradiol level is low. Thus, testosterone and DHEA hormone have a stronger effect in developing the process of CRC than the protecting effect of estradiol. Our findings confirmed the findings of other investigators (10). Our results showed that in CRC male patients the levels of HDLCh, LDL-Ch, TG, and TCh are high, compared to healthy controls, which was not confirmed in the findings of other investigators (11) because they used different study designs, had different populations, investigated different sample types, and utilized a variety of analytical methods to measure hormones (12). It is well known that estrogen supplementation can reduce the total and LDL- cholesterol concentration in women (12). Estrogen provoke the degradation of LDL cholesterol (13). Further, ROC curve analysis confirmed that serum testosterone, LH and FSH act as discriminatory factors to differentiate CRC patients from healthy controls. Therefore, serum testosterone, LH, and FSH could be used as markers to diagnose and monitor CRC and obtain positive outcomes in therapy. However, challenges remain for using lipid profile and steroid hormones as biomarkers in CRC and need to do more investigations.

5.1. Conclusions

The current study confirmed that serum levels of testosterone, estradiol, DHEA, and lipid profile

Altere d in patients with CRC. Therefore, the assessment of multiple markers (steroid hormones and lipid profile) might overcome and provide better judgments in patients with CRC.

5.2. Some Limitation Should Be Noted

The present study encountered some limitations. Firstly, our sample size was small. Secondly, we were unable to assess each stage, grade, and subtype of tumor progression.

Footnotes

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