KS Adedapo

• Several studies have shown that considerable overlap exists between prostate cancer and BPH in their pathogenesis and diagnostic modalities

• Prostate Specific Antigen (PSA) is a sensitive marker for PCa, but not sufficiently specific to differentiate between BPH and PCa at intermediate values

• a sensitive and specific biochemical marker that would complement tPSA and alleviate the potential harm and cost of screening associated with PSA-based screening, is imperative.

Micro and macro nutrients have been known to play prominent roles in pathogenesis and development of cancer.

Fats have been the focus of dietary studies of prostate cancer more than any other dietary component.

It has been known for about a century that cholesterol and other fatty deposits accumulate in solid tumours [1] Several studies have reported statistically significant correlations between cholesterol intake and cancer risk [2,3]

The human body is constantly under the attack of free radicals[4]

Free radicals are highly reactive molecules generated by the biochemical redox reactions that occur as part of normal cell metabolism

Increased level of serum lipid peroxide have been found in patients with benign prostate hyperplasia and cancer[5]

• We evaluated the possible diagnostic role of lipids, Vit. E, total antioxidant status (TAS), and trace metals (Se, Cu, Fe, Zn, and Mn) in 40 patients with histopathological diagnosis of BPH and Pca and control

• Fasting blood samples were collected for lipid analysis. Plasma samples were refrigerated at -20 0C until batch analysis within 2 weeks

• Plasma samples for total antioxidant status was determined by the method of Koracevic et al

Trace elements concentration was determined by an atomic absorption spectrophotometer (AAS) using a direct method previously described by Kaneko

Vit. E by the method of Baker Total cholesterol, HDL-cholesterol, LDL-

cholesterol, and Triglyceride concentration were determined by enzymatic method

Parameters Controls n=40 Pca n=40 BPH n=40 F, p-valuesAge (yrs) 65.2 (6.72) 68.5(9.6) 64.5(10.3) 2.25, 0.110Height (m) 1.7(0.08) 1.70(0.1) 1.70(0.1) 0.00, 1.000

Weight(kg) 69.6 (14.0) 60.5(14.9) 69.2(11.5) 5.77, 0.004*Hip circumference (cm)

99.4(1.9) 91.9(7.8) 97.7(6.3) 17.82, 0.000*

Waist circumference (cm)

87.4(11.3) 86.2(6.6) 90.1(8.7) 1.94, 0.148

BMI(k/m2) 23.9(4.6) 21.03(3.9) 24.0(4.6) 5.93, 0.004*

Systolic BP (mmHg)

137.7(29.0) 132.5(21.5) 138.6(22.4) 0.78, 0.488

Diastolic BP (mmHg)

91.1(129) 86.0(9.9) 92.3(14.7) 2.79, 0.065

Table: 1 Anthropometric measurement in subjects and controls (mean ±SD)

RESULT 1

Parameters Controls n=40 Pca n=40 BPH n=40 F, p-values

Total PSA(µg/L) 3.2(2.47) 92.7(60.5) 55.1(59.7) 33.5, 0.000*

Se( µg/dl) 59.7(12.3) 58.6(12.8) 57.6(11.2) 0.30, 0.741

Cu( µg/dl) 45.9(6.2) 43.6(9.5) 41.2(9.4) 3.05, 0.051*

Fe µg/dl 61.7(12.3) 60.6(12.8) 59.8(11.3) 0.25, 0.782

Zn( µg/ml) 114.4(25.2) 119.8(25.2) 126.0(22.4) 2.28, 0.107

Mn (µg/ml) 36.8(5.8) 37.1(7.9) 34.5(6.4) 1.77, 0.175

Vit E (mg/dl) 15.2 (1.6) 10.9(1.0) 10.9(2.6) 71.67, 0.000*

TAS (mmol/L) 1.2(0.43) 1.0(0.5) 1.0(0.4) 2.69, 0.072

T/Cholesterol(mg/dl) 157.1(27.5) 188.7(31.7) 155.1(49.8) 10.05, 0.000 *†

LDL/cholesterol(mg/dl) 84.9(4.6) 116.9(26.9) 108.0(37.4) 15.27, 0.000*

HDL/cholesterol(mg/dl) 48.6(19.3) 44.3(10.5) 49.9(14.7) 1.48, 0.233

Triglycerides(mg/dl) 114(63.1) 136.7(59.1) 87.9(27.7) 8.68, 0.000*†

Table: 2. Biochemical parameters in subjects and controls (mean ±SD)*Anova

†Post hoc significant difference between Pca and BPH

From the panel tested only the total cholesterol and triglyceride differed significantly between patients with BPH and prostate cancer patients

Cut-offs from ROC for BPH and prostate cancer at 88.9% sensitivity and 66.7% specificity (95% CI) were 88.5 and 161 mg/dl for triglycerides and cholesterol respectively. (Adedapo et al 2012)[6]

In 2013 We examined another cohort (ROC) with sensitivity and specificity of

70.8% and 68% respectively gave a discriminating cut-off value of 101.8mg/d) for triglyceride between participants with prostate cancer and benign prostatic hyperplasia participants[7]

To date 2 related studies examining the distinguishing probability of lipids, (Tc, LDLc, HDLc, TG), Vit. E, total antioxidant status (TAS), Trace elements, calcium and cadium

Background low socioeconomic setting A biomarker that is Affordable, ease of screening and preferably

non invasive Combined with tPSA, prostate ultrasound

could be useful

Initially both total cholesterol and Tg using ROC (88.9% sensitivity, 66.7% specificity)

Cut offs for discrimination stood at 88.5mg/dl for TG and 161mg/dl for Tc

Different set of patients different analyst and statisticians 70.8% sensitivity and specificity at 68% Tg of 101mg/dl

Is there any there any significant diff. 88.5 and 101mg/dl ?

Would larger multicentered studies sustain this finding?

Wuermli 2005[8] has noted the significant positive correlation between prostate cancer and hypertriglyceridaemia

More work needed in this area to validate the findings

Are there simple discriminating screening prospect for BPH and Pca?

Any prospect for disease prevention?

Diet has a central role to play, high fat, refined carbohydrate, and dairy certainly has a role to play, but to what extent.

Role of Calcium and Vit. D down regulation by

Dairy product through increased calcium [9]

The search continues!!

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3. R. Jarvinen, P. Knekt, T. Hakulinen, H. Rissanen, M. Heliovaara, Dietary fat, cholesterol and colorectal cancer in a prospective study, Br J Cancer, 2001, 85,357–3614

4. Okezie A, Harparkash K, Haliwell B: Oxygen free radicals and human diseases. J Roy Soc Health 1991, 34: 171-177.

5. Block G, Patterson B, Subar A : Fruit, vegetable and cancer prevention; a review of the epidemiological evidence. Nutr Cancer 1992; 18(1):1-29.

5. Srivastava DSL, Mittal RD: Free radical injury and antioxidant status in patients with benign prostate hyperplasia and prostate cancer. Indian Journal of Clinical Biochemistry. 2005, 20(2):162-165.

6. Adedapo KS, Arinola OG, Shittu OB, Kareem OI, Okolo CO, Nwobi LN, Diagnostic value of lipids, total antioxidants and trace metals in benign prostate hyperplasia and prostate cancer, Niger J Clin Prac, 2012;15: 293-297.

7. Adedapo KS, Olufemi O, Ogunwale KAT, Shittu OB. Could hypertriglyceridaemia be sustainable in discriminating between patients with prostate cancer from benign hypertrophy? Archives of Applied Science Research. 2014; 6 (4)(USA) (In press)

8. Wuermli L, Joeger M, Henz S, Schmid HP, Riesen WF, Thomas G, Hypertriglyceridaemia as a possible risk factor for prostate cancer, Prostate cancer Prostatic 2005, 8, 316-20

9. J.M. Chan, M.J. Stampfer, J. Ma, P.H. Gann, J.M. Gaziano, E.L. Giovannucci, Dairy products, calcium and prostate cancer risk in the Physicians’ study, Am J Clin Nutr, 2001, 74, 549-554.