Plasma Insulin-Like Growth Factor-1 (IGF-1), IGF-Binding Protein-3, and the Risk of Prostate Cancer: A Matched Case-Control Study in a Korean Population

Jeong Hyun Kim; Kwan Jin Park; Jung-Bum Bae; Woon Geol Yeo; Seok-Soo Byun; Eun Sik Lee

doi:10.4111/kju.2009.50.7.642

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Kim, Park, Bae, Yeo, Byun, and Lee: Plasma Insulin-Like Growth Factor-1 (IGF-1), IGF-Binding Protein-3, and the Risk of Prostate Cancer: A Matched Case-Control Study in a Korean Population

Original Article

Korean J Urol 2009;50(7):642-648.

Published online: 19 June 2009

DOI: https://doi.org/10.4111/kju.2009.50.7.642

Plasma Insulin-Like Growth Factor-1 (IGF-1), IGF-Binding Protein-3, and the Risk of Prostate Cancer: A Matched Case-Control Study in a Korean Population

Jeong Hyun Kim, Kwan Jin Park¹, Jung-Bum Bae¹, Woon Geol Yeo¹, Seok-Soo Byun¹, Eun Sik Lee^1,

¹From the Department of Urology, Kangwon National University College of Medicine, Chuncheon, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Eun Sik Lee Department of Urology, Seoul National University College of Medicine, 28, Yongon-dong, Chongno-gu, Seoul 110-744, Korea TEL: 02-2072-2915 FAX: 02-742-4665 E-mail: eslee@snu.ac.kr

Received 22 January 2009 Accepted 15 June 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose:

Conflicting results have been reported for western populations on associations of serum insulin-like growth factor I (IGF-I) and major IGF-binding protein-3 (IGFBP-3) with the risk of prostate cancer. However, few data have been available for oriental populations. We undertook a matched case-control study in a low-risk Korean population to extend our knowledge about potential associations.

Materials and Methods:

Serum IGF-I and IGFBP-3 levels were determined for 330 men (165 cases and 165 healthy age-matched controls). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between plasma IGF levels and prostate cancer. We also investigated the potential influence of the associations according to clinical risk for advanced disease at diagnosis.

Results:

We noted that the risks of prostate cancer were unrelated to the IGF-1 level and IGF-I/IGFBP-3 molar ratio. In contrast, a strong inverse association was observed between IGFBP-3 levels and the risk for prostate cancer. Men in the highest quartile of IGFBP-3 levels had a 71% reduced risk of prostate cancer compared with men in the lowest quartile (OR= 0.29, 95% CI: 0.11-0.64, Ptrend＜0.001). Subgroup analysis revealed a significant inverse association between plasma IGFBP-3 and the likelihood of a high risk prostate cancer.

Conclusions:

Plasma IGFBP-3 levels were inversely associated with the risk of prostate cancer and the likelihood for high-risk disease, suggesting that IGFBP-3 plays a protective role against prostate cancer in the Korean population.

Keywords: Prostatic neoplasms, Insulin-like growth factor I, Insulin-like growth factor binding protein 3

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Table 1.

Selected characteristics of cases with prostate cancer andof matched controls in a Korean population

	Prostate cancer (Mean±SD)	Control (Mean±SD)p-value^a
No. of patients	165	165
Age (years)	63.5±6.5	63.1±6.4	0.78
Height (cm)	164.6±6.4	165.8±5.5	0.16
Weight (kg)	68.2±7.4	65.8±6.9	0.06
Body mass index (m/kg²)	24.4±2.9	23.9±2.7	0.42
PSA (ng/ml)	12.68±17.1	1.30±1.0	＜0.001
Distribution of PSA
＜4	16	159
4-10	77	6
10.1-20	43	0
＞20	29	0
Gleason score
2-6	62
7	39
8-10	64
Risk stratification
Low	92
High	73

PSA: prostate-specific antigen,

^a : paired t-test between cases and controls

Table 2.

Mean plasma IGF-1 and IGFBP-3 concentrations in prostatecancer cases and matched controls in a selected Korean popu-ation

	Prostate cancer (Mean±SD)	Control (Mean±SD)	p-value	p after mutual adjustment
IGF-1	205.4±48.3	193.2±58.8	0.25	0.18
IGFBP-3	2,590.2±964.2	3,930.7±953.9	0.004	0.0001
IGF-1/ IGFBP-3	0.219±0.08 3	0.206±0.12	0.15

IGF-1: insulin-like growth factor-1, IGFBP-3: insulin-like growth factor binding protein-3

Table 3.

The risk of prostate cancer in relation to plasma levels of IGF-1, IGFBP-3, and their molar ratio

	Quartile	n (prostate cancer/control)	OR (95% CI)
	Quartile	n (prostate cancer/control)	Matched^a	Adjusted
IGF-1	Q1 (51-126 ng/ml)	41/41	1.00	1.00
	Q2 (127-168 ng/ml)	51/42	1.22 (0.64-2.18)	1.45 (0.58-2.67)^b
	Q3 (169-223 ng/ml)	31/41	0.76 (0.42-1.39)	0.71 (0.36-1.46)^b
	Q4 (224-682 ng/ml)	42/41	1.05 (0.45-1.54)	1.14 (0.55-1.85)^b
			P_trend=0.45	P_trend=0.24^b
IGFBP-3	Q1 (1,129-2,162 ng/ml)	58/41	1.00	1.00
	Q2 (2,163-3,086 ng/ml)	47/42	0.78 (0.35-0.98)	0.63 (0.28-0.96)^c
	Q3 (3,087-4,681 ng/ml)	39/41	0.67 (0.21-0.89)	0.56 (0.12-0.84)^c
	Q4 (4,682-5,947 ng/ml)	21/41	0.35 (0.14-0.66)	0.29 (0.11-0.64)^c
			P_trend=0.002	P_trend＜0.001^c
IGF-1/IGFBP-3	Q1 (0.065-0.143)	34/41	1.00	1.00
	Q2 (0.144-0.185)	41/42	1.15 (0.67-1.69)	1.38 (0.53-2.06)^d
	Q3 (0.186-0.237)	46/41	1.32 (0.92-2.15)	1.52 (0.88-2.36)^d
	Q4 (0.238-0.525)	44/41	1.29 (0.72-2.08)	1.48 (0.61-2.25)^d
			P_trend=0.18	P_trend=0.09^d

IGF-1: insulin-like growth factor-1, IGFBP-3: insulin-like growth factor binding protein-3.

^a : matched on age,

^b : adjusted for IGFBP-3, height, and body mass index (BMI); matched on age,

^c : adjusted for IGF-1, height, and BMI; matched on age,

^d : adjusted for height and BMI; matched on age, OR: odds ratio

Table 4.

Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer according to the plasma levels of IGF-1, IGFBP-3,and the molar ratio of IGF-1/IGFBP-3 by the dichotomized clinical risk for advanced disease

	Quartile^a	Low risk disease		High risk disease
	Quartile^a	n (prostate cancer/control)	OR (95% CI)	n (prostate cancer/control)	OR (95% CI)
IGF-1	Q1	21/23	1.00	18/18	1.00
	Q2	30/23	1.44 (0.84-3.54)	17/18	0.94 (0.52-2.31)
	Q3	24/23	1.10 (0.66-1.99)	16/19	0.82 (0.51-1.68)
	Q4	17/23	1.05 (0.46-2.29)	22/18	1.23 (0.76-3.53)
			P_trend=0.54		P_trend=0.31
IGFBP-3	Q1	25/23	1.00	28/18	1.00
	Q2	22/23	1.19 (0.42-1.36)	22/18	0.78 (0.31-1.15)
	Q3	26/23	1.04 (0.38-1.56)	16/19	0.57 (0.23-0.96)
	Q4	19/23	0.76 (0.36-1.44)	7/18	0.24 (0.06-0.78)
			P_trend=0.27		P_trend=0.01
IGF-1/IGFBP-3	Q1	19/23	1.00	16/18	1.00
	Q2	24/23	1.26 (0.72-3.17)	17/18	1.14 (0.78-1.99)
	Q3	24/23	1.27 (0.88-2.45)	16/19	1.03 (0.44-1.68)
	Q4	25/23	1.34 (0.91-3.06)	24/18	1.63 (1.04-2.75)
			P_trend=0.20		P_trend=0.26

IGF-1: insulin-like growth factor-1, IGFBP-3: insulin-like growth factor binding protein-3.

^a : the quartile cut point was based on the distributionof variable in the controls, OR: odds ratio

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