Tumor-associated epilepsy and glioma: Are there common genetic pathways?

Figures & data

Table I.  Some examples of case-control studies of gene polymorphisms showing associations with altered glioma risk

First Author	Gene and specific polymorphism	Tumor type	Number of cases and controls
Brenner [7]	CytokinesIL-4 (rs224348)IL-6 (rs1800795)	Glioma	756 cases,1190 controls
Rajaraman [8]	Cell cycleCCND1 (rs603965)CCNH (rs2266690)MDM2 (rs769412)	Glioma	388 cases,533 controls
Liu [9]	DNA repairERCC1 (3'UTR)XRCC1 (R399Q)APEX1 (E148D)PARP1 (A762V)MGMT (F84L)LIG1 (5ÚTR)	Glioma	373 cases,365 controls
Carpentier [10]	TelomerasehTERT (MNS16A)	Glioblastoma (GB)& Anaplastic astrocytoma (AA)	205 GB, 147 AA, 305 controls
Costa [11]	EGF (EGF + 61)	Glioma	197 cases,570 controls
Lu [12]	Promoter Matrix metalloproteinaseMMP-1-1607 1G/1GMMP-1 1G-MMP-3 6A	Astrocytoma	236 cases,366 controls
Parhar [13]	P53 codon 72P53 Arg72Pro	Glioma (including pediatric cases)	92 adult cases,43 pediatric cases,71 controls
Bhowmick [14]	EGF-receptor(EGFR 5ÚTR, G/A & G/G genotype)	Glioblastoma (GB)	31 primary GB,11 secondary GB78 controls
Wrensch [15]	Glutathione-S-transferaseGSTP I105V	GB, astrocytoma (A), oligodendro-glioma (OD), oli-goastrocytoma (OA)	179 GB, 62A, 94 OD or OA, 32 others,428 controls
Wang [16]	DNA repairXRCC/ G6721T (G/T& T/T genotype)	Glioma	309 cases,342 controls
Frigerio [17]	Tumour necrosis factorTNFb4	Glioblastoma	58 patients,95 controls

Figure 1.  MRI (T1-weighted images) of two patients with an oligodendroglioma (grade II) in the right frontal lobe, both presenting with focal epileptic seizures as the first symptoms. a) This patient became seizure-free on antiepileptic drugs after an initial seizure. b) This patient developed pharmacoresistent seizures in spite of multiple antiepileptic drugs.

Figure 2.  Immunohistochemical stainings with antibodies for the astrocytic marker GFAP (glial fibrillary acidic protein) of the peri-tumoural cortices of two different samples of diffuse astrocytomas (WHO grade II). a) A significant increase of reactive astrocytes is demonstrated in the peri-tumoural cortex of this patient with chronic epileptic seizures, compared tob) the peri-tumoural cortex of a patient who did not have any epileptic seizures.

Table II.  Case-control studies on polymorphisms of interleukins (IL) and focal epilepsy

First Author	Specific polymorphism	Epilepsy type	Nr of patients and controls	Outcome statistics and p-value
Kanemoto [33]	IL- 1β- 511	TLE-HS +	50 cases and 112 controls	χ^2=9.55p < 0.017
Kanemoto [34]	IL- 1β- 511	TLE-HS+ and PFC	66 cases,133 controls	TLE-HS+:χ^2=9.38p = 0.0022PFC:χ^2=9.90P = 0.0016
Ozkara [35]	IL-1β-511; IL-1β + 3953; IL-1α–889	TLE-HS +	47 cases,99 controls	NS
Heils [36]	IL-1β-511	TLE-HS +	86 cases,133 controls	χ^2=0.436p = 0.804
Buono [37]	IL-1β –511	TLE-HS +	61 cases,119 controls	χ^2=5.22p = 0.09
Jin [38]	IL-1β- 511	TLE-HS+ and TLE-HS-	112 cases,115 controls	NS

TLE: temporal lobe epilepsy.

TLE-HS+: temporal lobe epilepsy with hippocampal sclerosis.

TLE-HS-: temporal lobe epilepsy without hippocampal sclerosis.

PFC: prolonged febrile convulsions.

Table III.  Case-control studies on polymorphisms of GABA receptors and serotonin transporters and focal epilepsy

First Author	Gene, specific poly-morphisms	Epilepsy type	Number of patients and controls	P-value, odds ratio and confidence interval
Gambardella [39]	GABA (B) receptorG1465A	Non-lesional TLE	141 cases and 372 controls	OR = 6.47;CI = 2.02-20.75p = 0.003
Ma [40]	G1465A	TLE preceded by febrile seizures (FS)	120 cases,218 controls	NS
Ma [41]	GABRA1,GABRA5, GABRG2, GABRD	Familial focal epilepsy preceded by FS	74 cases,118 controls	NS
Manna [42]	Serotonin transporter(5-HTT)5-HTTLPR 5-HTTVNTR	TLE	276 cases,309 controls	5-HTTLPR:p = 0.0086;5-HTTVNTR: NS

Table IV.  Studies on polymorphisms of apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) and focal epilepsy

First Author	Gene, specific polymorphism	Epilepsy type	Type of study	Number of patients and control group	Statistics and P-value
Blumcke [43]	Apo E	TLE with or withoutAmmons horn sclerosis (AHS)	Genetic linkage study	125 patients(65 TLE-AHS+, 53 TLE-AHS-)	NS
Gambardella [44]	Apo E − 491 A/T	Non-lesional TLE	Case- control	63 patients,220 controls	NS
Yeni [45]	Apo E4	Mesial TLE–HS	Case- control	47 cases,62 controls	OR = 1.06CI = 0.38-2.95p > 0.05
Briellmann [46]	ApoE4	Chronic TLE	No controls	43 patients,31 HS +	ApoE4 may have impact on earlier onset of seizuresp = 0.004
Kanemoto [47]	ProBDNF240T	Focal epilepsy	Case- control	219 cases,311 controls	X^2=8.59p = 0.0034
Lohoff [48]	BDNFC240TVal66Met	TLE	Case- control	151 cases,189 controls	NS

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