Serum ferritin and the risk of early-onset colorectal cancer

Table 1 Demographics and clinical characteristics of patients diagnosed with early-onset colorectal cancer, n (%)

	Females (n = 48, 56.5%)	Males (n = 37, 43.5%)	Total (n = 85)
Demographic characteristics
Age (years, mean ± SD)	39.8 ± 4.9	41.5 ± 5.2	40.5 ± 5.1
Serum ferritin level
≤ 20 ng/mL	24 (50.0)	15 (40.5)	39 (45.9)
21-45 ng/mL	11 (22.9)	4 (10.8)	15 (17.6)
46-100 ng/mL	6 (12.5)	5 (13.5)	11 (12.9)
≥ 101 ng/mL	7 (14.6)	13 (35.1)	20 (23.5)
AJCC stage1
I	4 (8.3)	1 (2.7)	5 (6.0)
II	3 (6.3)	6 (16.2)	9 (10.7)
III	19 (39.6)	9 (24.3)	28 (33.3)
IV	21 (43.8)	21 (56.8)	42 (50.0)
Characteristics at diagnosis
Anemia	39 (81.3)	31 (83.8)	70 (82.4)
MCV < 80 fL	20 (41.7)	21 (56.8)	41 (48.2)
MCV >100 fL	2 (4.2)	1 (2.7)	3 (3.5)
Ferritin obtained before	9 (18.8)	5 (13.5)	14 (16.5)
Ferritin obtained at diagnosis	18 (37.5)	16 (43.2)	34 (40.0)
Ferritin obtained after	21 (43.8)	16 (43.2)	37 (43.5)

¹Stage was unknown in one patient, as they decided to opt out of further workup.

AJCC: American Joint Committee on Cancer; MCV: Mean corpuscular volume.

Table 2 Early-onset colorectal cancer vs healthy controls stratified by age, sex, and serum ferritin

	EO-CRC	Healthy controls	P value
Female: Age 29-39			Fisher’s exact: P = 0.029
Ferritin ≤ 20.0 ng/mL	13/20 (65.0%)	10931/34035 (32.1%)	0.002
20.1-45.0 ng/mL	3/20 (15.0%)	10626/34035 (31.2%)	0.116
45.1-100.0 ng/mL	2/20 (10.0%)	8039/34035 (23.6%)	0.153
≥ 100.1 ng/mL	2/20 (10.0%)	4439/34035 (13.0%)	0.689
Male: Age 29-39			Fisher’s exact: P = 0.0098
Ferritin ≤ 20.0 ng/mL	4/10 (40.0%)	423/5892 (7.2%)	< 0.00001
20.1-45.0 ng/mL	1/10 (10.0%)	825/5892 (14.0%)	0.719
45.1-100.0 ng/mL	1/10 (10.0%)	1738/5892 (29.5%)	0.177
≥ 100.1 ng/mL	4/10 (40.0%)	2906/5892 (49.3%)	0.555
Female: Age 40-49			Fisher’s exact: P = 0.456
Ferritin ≤ 20.0 ng/mL	11/28 (39.3%)	9364/32750 (28.6%)	0.211
20.1-45.0 ng/mL	8/28 (28.6%)	9947/32750 (30.4%)	0.834
45.1-100.0 ng/mL	4/28 (14.3%)	8230/32750 (25.1%)	0.187
≥ 100.1 ng/mL	5/28 (17.9%)	5209/32750 (15.9%)	0.779
Male: Age 40-49			Fisher’s exact: P < 0.00001
Ferritin ≤ 20.0 ng/mL	10/26 (38.5%)	519/7534 (6.9%)	< 0.00001
20.1-45.0 ng/mL	3/26 (11.5%)	920/7534 (12.2%)	0.920
45.1-100.0 ng/mL	4/26 (15.4%)	2021/7534 (26.8%)	0.187
≥ 100.1 ng/mL	9/26 (34.6%)	4074/7534 (54.1%)	0.047

For the purpose of this analysis, one patient in early-onset colorectal cancer (EO-CRC) cohort, age 22 years, was excluded to limit biases. Fisher’s exact test was used to compare the proportions of the different serum ferritin level groups between EO-CRC and healthy controls (HCs). Then post-hoc z-test of proportions were used to compare specific serum ferritin levels between EO-CRC and HCs. Patients were grouped by age and sex to minimize confounding factors.

Table 3 Median serum ferritin in patients diagnosed with early-onset colorectal cancer stratified by sex, American Joint Committee on Cancer stage, and anemia status

Median (IQR), ng/mL	Females (n = 45)	Males (n = 37)	Total (n = 82)
AJCC stage
I	23.5 (31.50)	8.01	13 (30.5)
II	6.02	4.0 (18.25)	9.0 (11.0)
III	13.0 (23.25)	21.0 (124.00)	14.0 (51.0)
IV	30.0 (45.00)	92.0 (170.00)	42.0 (106.0)
Anemia status
Yes	17.5 (25.50)	32.0 (127.00)	19.0 (49.00)
No	34.0 (47.00)	131.5 (97.00)	60.0 (130.00)
Sex	19.0 (31.50)	41.0 (142.00)	-

¹One case included, unable to calculate inter-quartile range (IQR).

²Three cases included, unable to calculate IQR.

Three outliers were removed with serum ferritin > 500 ng/mL [> quartile 3 (75^th percentile) plus 5 times IQR]. IQR: Inter-quartile range; AJCC: American Joint Committee on Cancer.

Table 4 Correlation analyses of serum ferritin by age and by months from diagnosis

Item	r	P value
Serum ferritin by age1
Total	0.281	0.011
Females	0.391	0.009
Males	0.086	0.618
Serum ferritin by months from diagnosis
Total	0.272	0.014
Females	0.052	0.733
Males	0.436	0.007

¹Adjusted for by American Joint Committee on Cancer Stage.