Sex-specific functional effect of IL-12 gene polymorphisms in brain tumours

Figures & data

Table 1. Histopathological type of tumour.

Histopathological type of tumour	Number of cases
Primary brain tumour	50
Meningioma	6
Epidermoid cysts	2
Astrocytomas grade I	2
Astrocytomas grade II	2
Astrocytomas grade III	3
Glioblastoma multiforme (grade IV)	35
Brain metastasis	70
Lung cancer	36
Colon or rectal	9
Kidney or bladders	5
Melanoma	4
Breast	3
Endometrium	2
Other/unknown	11

Table 2. Demographic and clinical parameters of the studied groups.

Characteristics	Brain tumours		Healthy volunteers	p Value
Number	120		240/331^a
Gender
Male, n (%)	65 (54%)		96 (40%) 119 (36%)	χ^2=6.495; p = .011; χ^2=12.098; p = .001
Female, n (%)	55 (46%)		144 (60%) 212 (64%)
Age
Mean ± SD, year	62.1 ± 10.55	39.4 ± 14.4/39.8 ± 12.7^a		p < .001 (t-test)
Min, year	28	24
Max, year	82	84
Tumour types
Low-grade glioma (WHO I–II), n (%)	4 (3%)
High-grade glioma (WHO III–IV), n (%)	38 (32%)
Meningioma, n (%)	6 (5%)
Other, n (%)	2 (2%)
Metastasis, n (%)	70 (58%)
Hemispheric location
Left, n (%)	49 (41%)
Right, n (%)	42 (35%)
Bihemispheric, n (%)	9 (7%)
Not applicable, n (%)	20 (17%)

^aControl group for IL12B rs3212227 polymorphism (n = 240) and for IL12B rs17860508 (n = 331); GBM: Glioblastoma Multiforme.

Table 3. Genetic models of the IL12B rs3212227 and rs17860508 polymorphisms among the cases with brain tumours and controls.

Rs3212227	Genotype/ variant	Cases, n (%) N = 120	Controls, n (%) N = 240	OR (95% CI); p value	Adjusted OR (95% CI); p value
Codominant model	AA	73 (61%)	134 (55.8%)	1.00	1.00
	AC	39 (32%)	85 (35.4%)	0.842 (0.52–1.35); p = .48	0.974 (0.53–1.8); p = .93
	CC	8 (7%)	21 (8.8%)	0.699 (0.3–1.66); p = .42	0.687 (0.23–2.04); p = .5
Dominant model	AA	73 (61%)	134 (55.8%)	1.00	1.00
	AC + CC	47 (39%)	106 (44.2%)	0.814 (0.52–1.27); p = .37	0.913 (0.51–1.62); p = .76
Recessive model	AA + AC	112 (93%)	219 (91.2%)	1.00	1.00
	CC	8 (7%)	21 (8.8%)	0.745 (0.32–1.74); p = .5	0.693 (0.24–2.01); p = .5
Overdominant model	AA + CC	81 (67.5%)	155 (64.6%)	1.00	1.00
	AC	39 (32.5%)	85 (35.4%)	0.878 (0.55–1.4); p = .58	1.017 (0.56–1.85); p = .96
Allelic model	A-allele	185 (77%)	353 (73.5%)	1.00	1.00
	C-allele	55 (23%)	127 (26.5%)	0.878 (0.63–1.22); p = .44	1.017 (0.67–1.56); p = .94
rs17860508	Genotype/ variant	Cases, n (%) N = 120	Controls, n (%) N = 331	OR (95% CI); p value	Adjusted OR (95% CI); p value
Codominant model	11	23 (19%)	97 (29%)	1.00	1.00
	12	52 (43%)	162 (49%)	1.354 (0.78–2.35); p = .28	1.004 (0.50–2.01); p = .99
	22	45 (38%)	72 (22%)	2.636 (1.47–4.74); p = .001	1.401 (0.66–2.98); p = .38
Dominant model	11	23 (19%)	97 (27%)	1.00	1.00
	12 + 22	97 (81%)	234 (71%)	1.748 (1.05–2.92); p = .033	1.154 (0.6–2.21); p = .67
Recessive model	11 + 12	75 (62.5%)	259 (78%)	1.00	1.00
	22	45 (37.5%)	72 (22%)	2.158 (1.37–3.39); p = .001	1.39 (0.77–2.52); p = .27
Overdominant model	11 + 22	68 (57%)	169 (51%)	1.00	1.00
	12	52 (43%)	162 (49%)	0.798 (0.52–1.22); p = .292	0.810 (0.47–1.39); p = .45
Allelic model	Allele-1	98 (41%)	356 (54%)	1.00	1.00
	Allele-2	142 (59%)	306 (46%)	1.686 (1.25–2.27); p = .001	1.214 (0.83–1.79); p = .33

Notes: BrM: brain metastasis; BT: brain tumours; OR: odds ration; 95% CI: 95% confidential interval; adjusted OR: adjusted odds ratio for age and sex; allele-1: TTAGAG allele of rs17860508; allele-2: GC allele of rs17860508. The significant associations are bolded.

Table 4. Association between rs3212227 and rs17860508 IL12B polymorphisms and risk of primary BT or BrM in inheritance models.

Rs3212227	Genotype/ variant	Primary BT, n (%) N = 50	Controls, n (%) N = 240	OR (95% CI); p value	Adjusted OR (95% CI); p value	BrM, n (%) N = 70	Controls, n (%) N = 240	OR (95% CI); p value	Adjusted OR (95% CI); p value
Codominant model	AA	35 (70%)	134 (55.8%)	1.00	1.00	38 (54%)	134 (55.8%)	1.00	1.00
	AC	14 (28%)	85 (35.4%)	0.631 (0.32–1.24); p = .182	0.72 (0.34–1.55); p = .402	25 (36%)	85 (35.4%)	1.037 (0.59–1.84); p = .901	1.249 (0.62–2.54); p = .538
	CC	1 (2%)	21 (8.8%)	0.182 (0.02–1.4); p = .102	0.174 (0.02–1.48); p = .110	7 (10%)	21 (8.8%)	1.175 (0.46–2.97); p = .733	1.248 (0.39–4.04); p = .712
Dominant model	AA	35 (70%)	134 (55.8%)	1.00	1.00	38 (54%)	134 (55.8%)	1.00	1.00
	AC + CC	15 (30%)	106 (44.2%)	0.542 (0.28–1.04); p = .067	0.445 (0.2–0.99); p = .048	32 (46%)	106 (44.2%)	1.065 (0.62–1.82); p = .819	1.054 (0.65–2.43); p = .503
Recessive model	AA + AC	49 (96%)	219 (91.2%)	1.00	1.00	63 (90%)	219 (91.2%)	1.00	1.00
	CC	1 (4%)	21 (8.8%)	0.213 (0.03–1.62); p = .135	0.193 (0.023–1.63); p = .131	7 (10%)	21 (8.8%)	1.159 (0.47–2.85); p = .748	1.146 (0.37–3.6); p = .815
Overdominant model	AA + CC	36 (72%)	155 (64.6%)	1.00	1.00	45 (64%)	155 (64.6%)	1.00	1.00
	AC	14 (28%)	85 (35.4%)	0.709 (0.36–1.4); p = .316	0.814 (0.38–1.74); p = .596	25 (36%)	85 (35.4%)	1.013 (0.58–1.77); p = .963	1.209 (0.61–2.41); p = .59
Allelic model	A-allele	84 (84%)	353 (73.5%)	1.00	1.00	101 (72%)	353 (73.5%)	1.00	1.00
	C-allele	16 (16%)	127 (26.5%)	0.529 (0.3–0.94); p = .029	0.442 (0.23–0.87); p = .018	39 (28%)	127 (26.5%)	1.073 (0.7–1.64); p = .742	1.005 (0.976–1.036); p = .731
rs17860508	Genotype/ variant	Primary BT, n (%) N = 50	Controls, n (%) N = 331	OR (95% CI); p value	Adjusted OR (95% CI); p value	BrM, n (%) N = 70	Controls, n (%) N = 331	OR (95% CI); p value	Adjusted OR (95% CI); p value
Codominant model	11	8 (16%)	97 (29%)	1.00	1.00	15 (21%)	97 (29%)	1.00	1.00
	12	23 (46%)	162 (49%)	1.721 (0.74–4.0); p = .207	1.301 (0.52–3.27); p = .576	29 (41%)	162 (49%)	1.158 (0.59–2.27); p = .67	0.819 (0.36–1.86); p = .819
	22	19 (38%)	72 (22%)	3.2 (1.33–7.72); p = .01	1.8 (0.68–1.4.79); p = .240	26 (37%)	72 (22%)	2.335 (1.15–4.73); p = .018	1.154 (0.48–2.78); p = .479
Dominant model	11	8 (16%)	97 (27%)	1.00	1.00	15 (21%)	97 (27%)	1.00	1.00
	12 + 22	42 (84%)	234 (71%)	2.176 (0.985–4.8); p = .054	1.482 (0.62–3.53); p = .374	55 (79%)	234 (71%)	1.52 (0.82–2.82); p = .184	0.948 (0.44–2.03); p = .891
Recessive model	11 + 12	31 (62%)	259 (78%)	1.00	1.00	44 (63%)	259 (78%)	1.00	1.00
	22	19 (38%)	72 (22%)	2.205 (1.18–4.13); p = .014	1.486 (0.72–3.05); p = .280	26 (37%)	72 (22%)	2.126 (1.23–3.69); p = .007	1.321 (0.67–2.62); p = .426
Overdominant model	11 + 22	27 (54%)	169 (51%)	1.00	1.00	41 (59%)	169 (51%)	1.00	1.00
	12	23 (46%)	162 (49%)	0.889 (0.49–1.61); p = .698	0.891 (0.46–1.74); p = .736	29 (41%)	162 (49%)	0.738 (0.44–1.24); p = .254	0.746 (0.39–1.42); p = .371
Allelic model	Allele-1	39 (39%)	356 (54%)	1.00	1.00	59 (42%)	356 (54%)	1.00	1.00
	Allele-2	61 (61%)	306 (46%)	1.82 (1.18–2.8); p = .006	1.486 (0.72–3.05); p = .28	81 (58%)	306 (46%)	1.597 (1.11–2.31); p = .013	1.321 (0.67–2.62); p = .426

Notes: BrM: brain metastasis; BT: brain tumours; OR: odds ration; 95% CI: 95% confidential interval; adjusted OR: adjusted odds ratio for age and sex; allele-1: TTAGAG allele of rs17860508; allele-2: GC allele of rs17860508. The significant associations are bolded.

Figure 1. Serum levels of IL-12p40 (A) and IL-23 (B) in cases with primary brain tumours (BT), brain metastasis (BrM) and controls in relation to sex. The data are mean values ± standard error.

Figure 2. Serum levels of IL-12p40 in cases with glioblastoma multiforme (GBM), primary brain tumours (BT), brain metastasis (BrM) and controls in association with sex and genotypes of the IL12B rs3212227 polymorphism.

Figure 3. Serum levels of IL-12p40 in cases with glioblastoma multiforme (GBM), primary brain tumours (BT), brain metastasis (BrM) and controls in association with sex and genotypes of the IL12B rs17860508 polymorphism.

Data availability statement

The data that support the findings of this study are available upon reasonable request from the corresponding author, LM. The data are not publicly available due to their containing information that could compromise the privacy of research participants.