. Author manuscript; available in PMC: 2018 Jul 26.

Published in final edited form as: J Clin Endocrinol Metab. 2017 May 1;102(5):1661–1672. doi: 10.1210/jc.2016-2046

Table 4.

Cancer^a mortality and incidence risks, SAGhE cohort, by demographic and GH treatment variables, and initial diagnosis leading to GH treatment


Demographic or treatment variable	All initial diagnoses, total
		Cancer mortality		Cancer incidence^c
		n	SMR^b (95% CI)	n	SMR (95% CI)

Sex	Male	138	12.4 (10.5-14.6)^g	52	2.2 (1.7-2.9)^g
Sex	Female	113	15.8 (13.1-19.0)^g	86	2.2 (1.8-2.7)^g
Country	Belgium	23	22.1 (14.7-33.3)^g	7	1.9 (0.9-4.0)
	France	88	9.9 (8.1-12.2)^g	-
	Germany	10	11.5 (6.2-21.4)^g	-
	Italy	1	1.7 (0.0-9.4)	-
	Netherlands	27	23.6 (16.2-34.5)^g	22	2.5 (1.6-3.8)^g
	Sweden	30	12.9 (9.0-18.5)^g	50	1.5 (1.2-2.0)^f
	Switzerland	6	19.7 (8.8-43.7)^g	2	2.5 (0.6-10.1)
	UK	66	20.7 (16.3-26.4)^g	57	3.4 (2.6-4.4)^g
Age started treatment (years)	0-4	9	7.1 (3.7-13.6)^g	7	1.7 (0.8-3.5)
	5-9	70	13.9 (11.0-17.6)^g	46	2.5 (1.8-3.3)^g
	10-14	149	15.4 (13.1-18.0)^g	71	2.1 (1.7-2.6)^g
	15-19	23	10.0 (6.6-15.0)^g	14	2.3 (1.4-3.9)^f
	p trend		0.55		1.00
Time since started treatment (years)	0-4	103	24.4 (20.1-29.6)^g	25	3.5 (2.4-5.2)^g
	5-9	78	17.2 (13.8-21.5)^g	21	1.8 (1.2-2.8)^e
	10-14	37	8.2 (6.0-11.4)^g	47	2.3 (1.8-3.1)^g
	15-19	25	6.7 (4.5-9.8)^g	30	1.6 (1.1-2.3)^e
	≥20	8	6.1 (3.1-12.3)^g	15	2.7 (1.7-4.6)^f
	p trend		<0.001		0.13
Duration of treatment (years)^d	<3	118	21.1 (17.6-25.3)^g	40	2.8 (2.1-3.9)^g
	3-6	80	12.4 (10.0-15.5)^g	52	2.7 (2.1-3.5)^g
	≥7	35	7.5 (5.4-10.4)^g	33	1.9 (1.3-2.6)^f
	p trend		<0.001		0.07
Mean GH dose (µg/kg/day)^d	<20	37	9.6 (7.0-13.3)^g	18	4.0 (2.6-6.4)^g
	20-9	94	19.5 (15.9-23.8)^g	40	3.3 (2.4-4.4)^g
	30-9	52	16.8 (12.8-22.0)^g	41	2.1 (1.6-2.9)^g
	≥40	7	3.8 (1.8-8.0)^f	11	1.1 (0.6-2.0)
	p trend		0.39		<0.001
Cumulative GH dose (mg/kg)^d	<25	91	14.9 (12.1-18.3)^g	38	3.4 (2.5-4.7)^g
	25-49	73	16.9 (13.4-21.2)^g	30	2.1 (1.5-3.0)^g
	50-99	36	11.1 (8.0-15.3)^g	40	2.3 (1.7-3.2)^g
	≥100	3	2.7 (0.9-8.3)	11	1.6 (0.9-2.9)
	p trend		0.003		0.02

Total		251	13.7 (12.1-15.5)^g	138	2.2 (1.9-2.6)^g


			Initial diagnosis cancer				Initial diagnosis non-cancer
			Cancer mortality		Cancer incidence ^c		Cancer mortality		Cancer incidence ^c
		n	SMR^b (95% CI)	n	SIR (95% CI)	n	SMR^b (95% CI)	n	SIR (95%CI)

Sex	Male	131	90.2 (76.0-107.0)^g	30	7.2 (5.0-10.3)^g	7	0.7 (0.3-1.5)	22	1.1 (0.7-1.7)
Sex	Female	99	123.1 (101.1-149.9)^g	42	8.0 (5.9-10.8)^g	14	2.2 (1.3-3.7)^e	44	1.3 (1.0-1.7)
Country	Belgium	20	113.9 (73.5-176.6)^g	3	5.0 (1.6-15.4)^e	3	3.5 (1.1-10.8)^e	4	1.3 (0.5-3.5)
	France	79	96.6 (77.5-120.5)^g	-		9	1.1 (0.6-2.2)	-
	Germany	9	114.9 (59.8-220.9)^g	-		1	1.3 (0.0-7.0)	-
	Italy	0	0.0 (0.0-252.6)	-		1	1.7 (0.0-9.6)		-
	Netherlands	26	138.2 (94.1-203.0)^g	14	9.9 (5.8-16.7)^g	1	1.0 (0.0-5.8)	8	1.1 (0.5-2.2)
	Sweden	27	120.6 (82.7-175.9)^g	21	5.6 (3.6-8.6)^g	3	1.4 (0.5-4.4)	29	1.0 (0.7-1.4)
	Switzerland	5	168.4 (70.1-404.5)^g	2	31.0 (7.7-123.9)^f	1	3.6 (0.1-20.2)	0	0.0 (0.0-5.1)
	UK	64	87.8 (68.7-112.1)^g	32	8.9 (6.3-12.6)^g	2	0.8 (0.2-3.3)	25	1.9 (1.3-2.8)^f
Age started treatment (years)	0-4	8	127.4 (63.7-254.7)^g	4	16.1 (6.1-43.0)^g	1	0.8 (0.0-4.6)	3	0.8 (0.2-2.4)
	5-9	65	100.1 (78.5-127.7)^g	18	7.1 (4.5-11.3)^g	5	1.1 (0.5-2.7)	28	1.7 (1.2-2.5)^f
	10-14	137	108.7 (91.9-128.5)^g	42	7.3 (5.4-9.9)^g	12	1.4 (0.8-2.5)	29	1.0 (0.7-1.5)
	15-19	20	70.3 (45.4-109.0)^g	8	8.6 (4.3-17.2)^g	3	1.5 (0.5-4.6)	6	1.2 (0.5-2.6)
	p trend		0.30		0.71		0.53		0.44
Time since started treatment (years)	0-4	100	184.8 (151.9-224.8)^g	20	16.0 (10.3-24.9)^g	3	0.8 (0.3-2.5)	5	0.9 (0.4-2.1)
	5-9	71	124.4 (98.6-157.0)^g	12	5.9 (3.4-10.5)^g	7	1.8 (0.8-3.7)	9	0.9 (0.5-1.8)
	10-14	33	60.7 (43.2-85.4)^g	24	8.2 (5.5-12.2)^g	4	1.0 (0.4-2.7)	23	1.3 (0.9-2.0)
	15-19	19	45.9 (29.3-71.9)^g	11	4.5 (2.5-8.2)^g	6	1.8 (0.8-4.0)	19	1.2 (0.7-1.8)
	≥20	7	37.4 (17.8-78.4)^g	5	6.1 (2.5-14.7)^f	1	0.9 (0.0-5.0)	10	2.2 (1.2-4.0)^e
	p trend		<0.001		0.005		0.65		0.11
Duration of treatment (years)	<3	110	174.9 (145.1-210.8)^g	25	10.4 (7.1-15.5)^g	8	1.6 (0.8-3.2)	15	1.3 (0.8-2.1)
	3-5	74	87.0 (69.3-109.3)^g	29	8.6 (6.0-12.4)^g	6	1.1 (0.5-2.4)	23	1.4 (1.0-2.2)^e
	≥6	31	50.2 (35.3-71.4)^g	12	4.0 (2.2-7.0)^g	4	1.0 (0.4-2.6)	21	1.4 (0.9-2.2)
	p trend		<0.001		0.006		0.76		0.77
Mean GH dose (µg/kg/day)	<20	35	64.1 (46.0-89.3)^g	12	6.5 (3.7-11.4)^g	2	0.6 (0.2-2.4)	6	2.3 (1.0-5.2)
	20-9	89	102.1 (82.9-125.6)^g	26	7.6 (5.2-11.2)^g	5	1.3 (0.5-3.0)	14	1.6 (0.9-2.7)
	30-9	50	178.9 (135.6-236.1)^g	19	10.2 (6.5-16.0)^g	2	0.7 (0.2-2.8)	22	1.3 (0.8-1.9)
	≥40	5	101.5 (42.3-243.9)^g	3	5.0 (1.6-15.5)^e	2	1.1 (0.3-4.5)	8	0.9 (0.4-1.7)
	p trend		<0.001		0.59		0.74		0.05
Cumulative GH dose (mg/kg)	<25	87	108.8 (88.2-134.2)^g	25	9.9 (6.7-14.6)^g	4	0.8 (0.3-2.0)	13	1.5 (0.9-2.6)
	25-49	70	108.1 (85.5-136.7)^g	18	6.6 (4.1-10.4)^g	3	0.8 (0.3-2.5)	12	1.0 (0.6-1.8)
	50-99	30	79.5 (55.6-113.6)^g	18	6.8 (4.3-10.9)^g	6	2.1 (0.9-4.6)	22	1.5 (1.0-2.3)
	≥100	2	34.2 (8.6-136.9)^f	5	9.6 (4.0-23.1)^g	1	0.9 (0.0-5.3)	6	1.0 (0.4-2.1)
	p trend		0.05		0.43		0.24		0.63

Total		230	101.9 (89.6-116.0)^g	72	7.6 (6.1-9.6)^g	21	1.3 (0.9-2.0)	66	1.2 (1.0-1.6)

SMR = Standardised mortality ratio; SIR = Standardised incidence ratio; CI = Confidence interval

All malignancies except non-melanoma skin cancer.

Using Swiss rates as expecteds for Germany, and Belgian rates as expecteds for both France and the Netherlands, for cancer sites for which sufficient detail was not available from home-country national rates.

Excluding France, Germany and Italy.

Unknown, all initial diagnoses: duration of treatment mortality 18, incidence 13; mean GH dose mortality 61, incidence 28; cumulative GH dose mortality 48, incidence 19.

p<0.05