American Association for Cancer Research

Table 2.

Circulating levels of IGF-I and IGF-II and breast cancer risk (estimates in bold are adjusted for circulating levels of IGFBP-3 and those in italics are for the IGF-I/IGFBP-3 ratio)

Reference	Cases			Controls			OR* (95% CI)	P_{linear trend}^†	Unit or category of analysis
Reference		n	Mean (SD) or median (range), ng/mL	n	Mean (SD) or median (range), ng/mL		OR* (95% CI)	P_{linear trend}^†	Unit or category of analysis
IGF-I
Premenopausal women^‡
Case-control studies
Petridou et al. (32)	14	182 (50)	15	197 (62)	0.4^AS (0.1-1.4)	0.16	per 1 SD
Yu et al. (29)	171	163 (41-334)	170	146 (69-299)	2.29^ADR (1.20-4.37)	0.012	U3 vs L3
Yu et al. (29)	171	163 (41-334)	170	146 (69-299)						1.92^ADR (0.88-4.20)	0.236	U3 vs L3
Hirose et al. (33)	88	190 (86-390)	79	190 (95-420)	0.88 (0.41-1.88)	0.741	U3 vs L3
Hirose et al. (33)	88	190 (86-390)	79	190 (95-420)						0.86^AR (0.32-2.29)	0.783	U3 vs L3
Prospective studies
Hankinson et al. (27)	76	204 (40-425)	105	184 (81-320)	2.33 (1.06-5.16)	0.08	U3 vs L3
										2.88 (1.21-6.85)	0.02	U3 vs L3
										2.13 (0.97-4.68)	NA	U3 vs L3 IGF-I/IGFBP-3
		60 <51 y at blood draw	206 (78-425)	78	175 (85-320)	4.58 (1.75-12.0)	0.02	U3 vs L3
										7.28 (2.40-22.0)	0.01	U3 vs L3
										2.46 (0.97-6.24)	NA	U3 vs L3 IGF-I/IGFBP-3
Toniolo et al. (35)	172	215 (64)	486	213 (66)	1.60^AR (0.91-2.81)	0.09	U4 vs L4
	172	215 (64)	486	213 (66)						1.49^AR (0.80-2.79)	NA	U4 vs L4
		96 <51 y at dx	232 (60)	280	223 (67)	2.30^AR (1.07-4.94)	0.03	U4 vs L4
		96 <51 y at dx	232 (60)	280	223 (67)					1.90^AR (0.82-4.42)	NA	U4 vs L4
Kaaks et al. (34)	116	NA	330	NA	0.63 (0.29-1.39)	0.51	U4 vs L4
Krajcik et al. (30)	66	258 (86)	66	244 (90)	3.49^A (0.65-18.7)	0.051	U4 vs L4
Krajcik et al. (30)	66	258 (86)	66	244 (90)						2.01^A (0.33-12.4)	0.24	U4 vs L4
Muti et al. (31)	69	170 (55)	265	159 (60)	3.12^ARS (1.13-8.60)	0.01	U4 vs L4
		36 <48 y at dx	NA	138	NA	1.52^A (0.50-4.60)	NA	U3 vs L3
		33 >48 y at dx	NA	127	NA	15.43^A (3.25-73)	NA	U3 vs L3
Postmenopausal women^‡
Case-control studies
Jernström et al. (26)^§	45	120 (41)	393	127 (54)	1.00^∥ (1.00-1.00)	0.44	Per rank^∥
Agurs-Collins et al. (36)	30	167 (33)	30	133 (50)	1.183^A (1.167-1.201)	<0.05	Per 10 ng/mL
Petridou et al. (32)	61	144 (56)	60	142 (54)	1.1^AS (0.7-1.7)	0.59	Per 1 SD
Yu et al. (29)	128	114 (31-280)	130	106 (34-350)	1.97^ADR (0.93-4.19)	0.042	U3 vs L3
Yu et al. (29)	128	114 (31-280)	130	106 (34-350)						1.56^ADR (0.68-3.57)	0.166	U3 vs L3
Hirose et al. (33)	99	160 (73-310)	111	160 (59-370)	1.48 (0.73-3.02)	0.277	U3 vs L3
Hirose et al. (33)	99	160 (73-310)	111	160 (59-370)						1.30^AR (0.48-3.42)	0.594	U3 vs L3
Prospective studies
Hankinson et al. (27)	305	142 (21-390)	483	153 (24-464)	0.85 (0.53-1.39)	0.63	U5 vs L5
Hankinson et al. (27)	305	142 (21-390)	483	153 (24-464)						0.89 (0.51-1.55)	0.99	U5 vs L5
Toniolo et al. (35)	115	167 (52)	220	173 (67)	0.95^R (0.49-1.86)	0.87	U4 vs L4
Kaaks et al. (34)	274	NA	519	NA	1.29 (0.80-2.07)	0.15	U4 vs L4
Krajcik et al. (30)	60	227 (71)	60	243 (76)	0.77^A (0.23-2.56)	0.067	U4 vs L4
Krajcik et al. (30)	60	227 (71)	60	243 (76)						1.22^A (0.21-6.78)	0.74	U4 vs L4
Muti et al. (31)	64	124 (44)	238	130 (50)	0.58^ARS (0.24-1.36)	0.25	U4 vs L4
Keinan-Boker et al. (37)	149	NA	333	NA	1.1^AR (0.6-2.1)	NA	U4 vs L4
Keinan-Boker et al. (37)	149	NA	333	NA						0.7^AR (0.3-1.5)	NA	U4 vs L4
All women^‡
Case-control studies
Bruning et al. (10)	109	NA	279	NA	7.34^AR (1.67-32.16)	0.006	U5 vs L5 IGF-I/IGFBP-3
Li et al. (38)	40	106 (40-253)	40	97 (39-202)	1.75 (0.70-4.37)	0.229	U2 vs L2
										2.00^R (0.43-9.28)	0.376	U2 vs L2
										2.25^R (0.72-7.01)	0.164	U2 vs L2 IGF-I/IGFBP-37
IGF-II
Case-control studies
Li et al. (38)	40 premenopausal and postmenopausal	605 (255-1,020)	40	613 (267-900)	0.71 (0.29-1.72)	0.446	U2 vs L2
Li et al. (38)	40 premenopausal and postmenopausal	605 (255-1,020)	40	613 (267-900)						0.53^R (0.15-1.83)	0.318	>U2 vs L2
Yu et al. (29)	171 premenopausal	852 (326-1,857)	170	867 (407-1,386)	1.50^ADR (0.51-4.44)	0.439	U3 vs L3
Yu et al. (29)		128 postmenopausal	867 (362-1,472)	130	810 (454-1,430)	2.17^ADR (0.60-7.90)	0.367	U3 vs L3

Reference	Cases			Controls			OR* (95% CI)	P_{linear trend}^†	Unit or category of analysis
Reference		n	Mean (SD) or median (range), ng/mL	n	Mean (SD) or median (range), ng/mL		OR* (95% CI)	P_{linear trend}^†	Unit or category of analysis
IGF-I
Premenopausal women^‡
Case-control studies
Petridou et al. (32)	14	182 (50)	15	197 (62)	0.4^AS (0.1-1.4)	0.16	per 1 SD
Yu et al. (29)	171	163 (41-334)	170	146 (69-299)	2.29^ADR (1.20-4.37)	0.012	U3 vs L3
Yu et al. (29)	171	163 (41-334)	170	146 (69-299)						1.92^ADR (0.88-4.20)	0.236	U3 vs L3
Hirose et al. (33)	88	190 (86-390)	79	190 (95-420)	0.88 (0.41-1.88)	0.741	U3 vs L3
Hirose et al. (33)	88	190 (86-390)	79	190 (95-420)						0.86^AR (0.32-2.29)	0.783	U3 vs L3
Prospective studies
Hankinson et al. (27)	76	204 (40-425)	105	184 (81-320)	2.33 (1.06-5.16)	0.08	U3 vs L3
										2.88 (1.21-6.85)	0.02	U3 vs L3
										2.13 (0.97-4.68)	NA	U3 vs L3 IGF-I/IGFBP-3
		60 <51 y at blood draw	206 (78-425)	78	175 (85-320)	4.58 (1.75-12.0)	0.02	U3 vs L3
										7.28 (2.40-22.0)	0.01	U3 vs L3
										2.46 (0.97-6.24)	NA	U3 vs L3 IGF-I/IGFBP-3
Toniolo et al. (35)	172	215 (64)	486	213 (66)	1.60^AR (0.91-2.81)	0.09	U4 vs L4
	172	215 (64)	486	213 (66)						1.49^AR (0.80-2.79)	NA	U4 vs L4
		96 <51 y at dx	232 (60)	280	223 (67)	2.30^AR (1.07-4.94)	0.03	U4 vs L4
		96 <51 y at dx	232 (60)	280	223 (67)					1.90^AR (0.82-4.42)	NA	U4 vs L4
Kaaks et al. (34)	116	NA	330	NA	0.63 (0.29-1.39)	0.51	U4 vs L4
Krajcik et al. (30)	66	258 (86)	66	244 (90)	3.49^A (0.65-18.7)	0.051	U4 vs L4
Krajcik et al. (30)	66	258 (86)	66	244 (90)						2.01^A (0.33-12.4)	0.24	U4 vs L4
Muti et al. (31)	69	170 (55)	265	159 (60)	3.12^ARS (1.13-8.60)	0.01	U4 vs L4
		36 <48 y at dx	NA	138	NA	1.52^A (0.50-4.60)	NA	U3 vs L3
		33 >48 y at dx	NA	127	NA	15.43^A (3.25-73)	NA	U3 vs L3
Postmenopausal women^‡
Case-control studies
Jernström et al. (26)^§	45	120 (41)	393	127 (54)	1.00^∥ (1.00-1.00)	0.44	Per rank^∥
Agurs-Collins et al. (36)	30	167 (33)	30	133 (50)	1.183^A (1.167-1.201)	<0.05	Per 10 ng/mL
Petridou et al. (32)	61	144 (56)	60	142 (54)	1.1^AS (0.7-1.7)	0.59	Per 1 SD
Yu et al. (29)	128	114 (31-280)	130	106 (34-350)	1.97^ADR (0.93-4.19)	0.042	U3 vs L3
Yu et al. (29)	128	114 (31-280)	130	106 (34-350)						1.56^ADR (0.68-3.57)	0.166	U3 vs L3
Hirose et al. (33)	99	160 (73-310)	111	160 (59-370)	1.48 (0.73-3.02)	0.277	U3 vs L3
Hirose et al. (33)	99	160 (73-310)	111	160 (59-370)						1.30^AR (0.48-3.42)	0.594	U3 vs L3
Prospective studies
Hankinson et al. (27)	305	142 (21-390)	483	153 (24-464)	0.85 (0.53-1.39)	0.63	U5 vs L5
Hankinson et al. (27)	305	142 (21-390)	483	153 (24-464)						0.89 (0.51-1.55)	0.99	U5 vs L5
Toniolo et al. (35)	115	167 (52)	220	173 (67)	0.95^R (0.49-1.86)	0.87	U4 vs L4
Kaaks et al. (34)	274	NA	519	NA	1.29 (0.80-2.07)	0.15	U4 vs L4
Krajcik et al. (30)	60	227 (71)	60	243 (76)	0.77^A (0.23-2.56)	0.067	U4 vs L4
Krajcik et al. (30)	60	227 (71)	60	243 (76)						1.22^A (0.21-6.78)	0.74	U4 vs L4
Muti et al. (31)	64	124 (44)	238	130 (50)	0.58^ARS (0.24-1.36)	0.25	U4 vs L4
Keinan-Boker et al. (37)	149	NA	333	NA	1.1^AR (0.6-2.1)	NA	U4 vs L4
Keinan-Boker et al. (37)	149	NA	333	NA						0.7^AR (0.3-1.5)	NA	U4 vs L4
All women^‡
Case-control studies
Bruning et al. (10)	109	NA	279	NA	7.34^AR (1.67-32.16)	0.006	U5 vs L5 IGF-I/IGFBP-3
Li et al. (38)	40	106 (40-253)	40	97 (39-202)	1.75 (0.70-4.37)	0.229	U2 vs L2
										2.00^R (0.43-9.28)	0.376	U2 vs L2
										2.25^R (0.72-7.01)	0.164	U2 vs L2 IGF-I/IGFBP-37
IGF-II
Case-control studies
Li et al. (38)	40 premenopausal and postmenopausal	605 (255-1,020)	40	613 (267-900)	0.71 (0.29-1.72)	0.446	U2 vs L2
Li et al. (38)	40 premenopausal and postmenopausal	605 (255-1,020)	40	613 (267-900)						0.53^R (0.15-1.83)	0.318	>U2 vs L2
Yu et al. (29)	171 premenopausal	852 (326-1,857)	170	867 (407-1,386)	1.50^ADR (0.51-4.44)	0.439	U3 vs L3
Yu et al. (29)		128 postmenopausal	867 (362-1,472)	130	810 (454-1,430)	2.17^ADR (0.60-7.90)	0.367	U3 vs L3

NOTE: dx, diagnosis of breast cancer; L2 (U2), L3 (U3), L4 (U4), L5 (U5), lowest (highest) half, third, quarter, and fifth of the IGF-I/IGF-II distributions.

Cases and controls matched as indicated in Table 1; analysis further adjusted for anthropometric (A), dietary (D), reproductive (R), and socioeconomic (S) variables.

†

P for linear trend, unless there were only two categories (U2 vs L2) being compared.

‡

Menopausal status as ascertained at the time of blood collection expect for Krajcik et al. (30) where it refers to the time of diagnosis of breast cancer. The study by Kaaks et al. (34) did not stratify by menopausal status but provided data separately for premenopausal age (<50 y) and postmenopausal age (≥55 y). Results for all women combined are shown here only when no data stratified by menopausal status were available in the original articles.

This study was nested within a large prospective study but was classified here as a case-control study because blood samples were collected after breast cancer diagnosis.

∥

Women were ranked according to their IGF-I levels from lowest to highest. ORs adjusted for age. Further adjustment for anthropometric and reproductive variables did not affect the results (but no OR value is given in the article).

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