Eosinophilia in routine blood samples as a biomarker for solid tumor development – A study based on The Copenhagen Primary Care Differential Count (CopDiff) Database

Figures & data

Figure 1. Flowchart. CGPL, Copenhagen General Practitioners’ Laboratory; CopDiff, Copenhagen Primary Care Differential Count Database; CRS, The Danish Civil Registration System; DIFF, differential cell count; GP, general practitioner.

Table I. Patient characteristics.

Factor	N (%) or Median (IQR, range)
Gender
Male	151 259 (42)
Female	208 691 (58)
Age, years	48.3 (33.9–61.6, 18.0–80.0)
Eosinophilia
No (≤ 0.5 × 10^9/l)	341 790 (96.0)
Mild (≥ 0.5–1.0 × 10^9/l)	13 118 (3.7)
Severe (≥ 1.0 × 10^9/l)	1288 (0.3)
Previous eosinophilia (< 6 months)
Only negative tests	30 104 (8.4)
At least one positive test	2371 (0.7)
No blood test	327 475 (91.0)
Charlson's Comorbidity Index^a	0 (0–0, 0–16)
C-reactive protein
Normal	181 162 (50.4)
Increased^b	48 349 (13.5)
No blood test	129 755 (36.1)

Values are numbers (column %) or median (interquartile range, range).

^aCalculated on previous hospital contacts (< 3 years); ^b ≥ 10 mg/l.

Table II. The association between eosinophilia and 3-year incidence of solid tumors (n = 356 196).

Eosinophilia	Previous malignancy (since 1977) n (%)	Incident malignancy
		n (%)	Odds ratio (95% CI)	p-value
All solid tumors
No (< 0.5 × 10^9/l), n = 341 790	21 310 (6.2)	11 115 (3.5)	1.00	0.39^†
Mild (≥ 0.5–1.0 × 10^9/l), n = 13 118	823 (6.3)	481 (3.9)	0.94 (0.85–1.03)	0.18
Severe (≥ 1.0 × 10^9/l), n = 1288	117 (9.1)	54 (4.6)	0.98 (0.74–1.30)	0.90
All buccal cavity and pharynx
No	488 (0.1)	312 (0.1)	1.00	0.81^†
Mild	30 (0.2)	12 (0.1)	0.85 (0.47–1.51)	0.57
Severe	0 (0)	1 (0.1)	0.75 (0.11–5.37)	0.78
All digestive organs
No	2172 (0.6)	2441 (0.7)	1.00	0.77^†
Mild	71 (0.5)	129 (1.0)	1.06 (0.89–1.28)	0.51
Severe	18 (1.4)	16 (1.3)	1.10 (0.66–1.82)	0.72
–Colon
No	1109 (0.3)	919 (0.3)	1.00	0.68^†
Mild	38 (0.3)	47 (0.4)	1.02 (0.75–1.37)	0.92
Severe	9 (0.7)	8 (0.6)	1.40 (0.69–2.84)	0.36
–Rectum
No	563 (0.2)	400 (0.1)	1.00	0.14^†
Mild	16 (0.1)	30 (0.2)	1.50 (1.03–2.19)	0.04
Severe	3 (0.2)	2 (0.2)	0.90 (0.22–3.64)	0.88
All respiratory system and intrathoracic organs
No	1123 (0.3)	1971 (0.6)	1.00	0.27^†
Mild	47 (0.4)	114 (0.9)	1.18 (1.00–1.43)	0.10
Severe	12 (0.9)	12 (0.9)	0.99 (0.55–1.75)	0.94
–Lung
No	833 (0.2)	1830 (0.5)	1.00	0.24^†
Mild	37 (0.3)	107 (0.8)	1.19 (0.98–1.46)	0.09
Severe	11 (0.9)	11 (0.9)	0.95 (0.52–1.74)	0.89
All bones, joints and articular cartilage
No	38 (0.0)	7 (0.0)	1.00	-
Mild	1 (0.0)	0 (0)	-	-
Severe	0 (0)	0 (0)	-	-
All skin
No	7875 (2.3)	2890 (0.9)	1.00	0.0070^†
Mild	325 (2.5)	99 (0.8)	0.79 (0.64–0.97)	0.021
Severe	32 (2.5)	6 (0.5)	0.47 (0.21–1.05)	0.06
–Melanoma
No	1089 (0.3)	378 (0.1)	1.00	0.96^†
Mild	38 (0.3)	16 (0.1)	0.96 (0.58–1.61)	0.89
Severe	4 (0.3)	2 (0.2)	1.18 (0.29–4.80)	0.81
All mesothelium and connective tissue
No	138 (0.0)	81 (0.0)	1.00	0.65^†
Mild	8 (0.1)	4 (0.0)	1.23 (0.45–3.38)	0.68
Severe	1 (0.1)	1 (0.1)	2.73 (0.38–19.78)	0.32
All breast
No	4276 (1.3)	1313 (0.4)	1.00	0.079^†
Mild	102 (0.8)	28 (0.2)	0.66 (0.46–0.97)	0.035
Severe	17 (1.3)	5 (0.4)	1.00 (0.41–2.43)	0.99
All female genital organs
No	1852 (0.5)	548 (0.3)	1.00	0.90^†
Mild	42 (0.3)	16 (0.3)	0.90 (0.54–1.48)	0.67
Severe	8 (0.6)	2 (0.3)	0.88 (0.22–3.54)	0.85
–Cervix uteri
No	591 (0.3)	106 (0.1)	1.00	0.62^†
Mild	6 (0.1)	5 (0.1)	1.40 (0.56–3.50)	0.48
Severe	1 (0.2)	1 (0.2)	2.34 (0.32–17.20)	0.40
–Corpus uteri
No	798 (0.4)	179 (0.1)	1.00	0.25^†
Mild	23 (0.4)	3 (0.1)	0.53 (0.17–1.66)	0.27
Severe	6 (0.9)	0 (0)	-	-
–Ovary
No	389 (0.2)	236 (0.1)	1.00	0.59^†
Mild	12 (0.2)	6 (0.1)	0.79 (0.35–1.80)	0.58
Severe	1 (0.2)	2 (0.3)	1.95 (0.50–8.01)	0.35
All male genital organs incl. skin
No	1399 (1.0)	1225 (0.9)	1.00	0.12^†
Mild	77 (1.1)	56 (0.8)	0.77 (0.59–1.02)	0.07
Severe	10 (1.6)	5 (0.8)	0.70 (0.29–1.70)	0.43
–Prostate
No	918 (0.7)	1148 (0.8)	1.00	0.21^†
Mild	57 (0.8)	54 (0.8)	0.80 (0.60–1.05)	0.11
Severe	6 (0.9)	5 (0.8)	0.74 (0.30–1.80)	0.50
All urinary tract
No	1613 (0.5)	857 (0.3)	1.00	0.024^†
Mild	103 (0.8)	62 (0.5)	1.38 (1.06–1.81)	0.017
Severe	15 (1.2)	9 (0.7)	1.80 (0.92–3.51)	0.09
–Kidney
No	314 (0.1)	251 (0.1)	1.00	0.36^†
Mild	25 (0.2)	9 (0.1)	0.63 (0.32–1.25)	0.19
Severe	2 (0.2)	2 (0.2)	1.11 (0.27–4.55)	0.89
–Bladder
No	390 (0.1)	265 (0.1)	1.00	0.0047^†
Mild	25 (0.2)	28 (0.2)	1.93 (1.29–2.89)	0.0013
Severe	4 (0.3)	4 (0.3)	2.42 (0.89–6.60)	0.084
All eyes, brain and other parts of the central nervous system
No	907 (0.3)	538 (0.2)	1.00	0.09^†
Mild	33 (0.3)	17 (0.1)	0.82 (0.50–1.33)	0.41
Severe	3 (0.2)	0 (0)	-	-
–Brain
No	124 (0.0)	197 (0.1)	1.00	0.16^†
Mild	4 (0.0)	4 (0.0)	0.51 (0.19–1.39)	0.19
Severe	0 (0)	0 (0)	-	-
All endocrine glands
No	176 (0.1)	96 (0.0)	1.00	0.51^†
Mild	11 (0.1)	5 (0.0)	1.47 (0.60–3.63)	0.40
Severe	1 (0.1)	0 (0)	-
All-cause death
No		17 925 (5.0)	1.00	< 0.0001^†
Mild		1060 (8.1)	1.12 (1.04–1.21)	0.0031
Severe		196 (15.2)	1.85 (1.53–2.25)	< 0.0001

Values are numbers (%) of the eosinophilia group in question and odds ratios (95%) and p-values for the defined outcomes from multivariable logistic regression analysis adjusted for sex, age (quadratic), year, month, C-reactive protein, previous eosinophilia and co-morbidities (Charlson's Comorbidity Index). Individuals with previous cancer were omitted from the analyses (n = 22 250). ^†p-value for the likelihood-ratio test of all categories of eosinophilia simultaneously.