Interleukin-18 promoter genotype is associated with the risk of nasopharyngeal carcinoma in Taiwan

Figures & data

Table 1 Demographic characteristics of the investigated NPC patients and noncancer healthy controls

Characteristics	Controls (n=352)			Cases (n=176)			P-valuea
	n	%	Mean (SD)	n	%	Mean (SD)
Age (years)			48.7 (10.8)			49.3 (9.4)	0.7138
Gender							1.0000
Male	256	72.7		128	72.7
Female	96	27.3		48	27.3
Behavioral habits
Cigarette smoker	150	42.6		73	41.4		0.8519
Alcohol drinker	124	35.2		72	40.9		0.2150
Areca chewer	115	32.7		54	30.7		0.6926
Classification
KSCC (WHO type I)				5	2.8
NKC (WHO type II)				171	97.2
NKDC (WHO type IIa)				28	15.9
NKUC (WHO type IIb)				143	81.3

Note:

a Based on chi-squared test or Student’s t-test.

Abbreviations: KSCC, keratinizing squamous cell carcinoma; NKC, non-keratinizing carcinoma; NKDC, non-keratinizing differentiated carcinoma; NKUC, non-keratinizing undifferentiated carcinoma; NPC, nasopharyngeal carcinoma.

Table 2 Distribution of IL-18 genotypes among the NPC patients and noncancer healthy controls

	Controls		Patients		OR (95% CI)	OR (95% CI)a	P-valueb
	n	%	n	%
IL-18-656
AA	134	38.0	64	36.4	1.00 (reference)	1.00 (reference)
AC	150	42.6	80	45.4	1.12 (0.75–1.67)	1.02 (0.68–1.43)	0.5913
CC	68	19.3	32	18.2	0.99 (0.59–1.65)	1.03 (0.62–1.71)	0.9550
Ptrendc							0.9326
Carrier comparison
AA+AC	284	80.7	144	81.8	1.00 (reference)	1.00 (reference)
CC	68	19.3	32	18.2	0.93 (0.58–1.48)	0.98 (0.62–1.30)	0.7534
AA	134	38.0	64	36.4	1.00 (reference)	1.00 (reference)
AC+CC	218	62.0	112	63.6	1.07 (0.74–1.57)	1.03 (0.83–1.39)	0.7029
IL-18-607
AA	86	24.4	59	33.5	1.00 (reference)	1.00 (reference)
AC	178	50.6	87	49.4	0.71 (0.47–1.03)	0.73 (0.43–1.07)	0.1121
CC	88	25.0	30	17.1	0.50 (0.29–0.84)	0.46 (0.25–0.78)	0.0093
Ptrendc							0.0090
Carrier comparison
AA+AC	264	75.0	146	82.9	1.00 (reference)	1.00 (reference)
CC	88	25.0	30	17.1	0.62 (0.39–0.98)	0.59 (0.37–0.89)	0.0386
AA	86	24.4	59	33.5	1.00 (reference)	1.00 (reference)
AC+CC	266	75.6	117	66.7	0.64 (0.43–0.95)	0.61 (0.51–0.86)	0.0274
IL-18-137
GG	281	79.8	133	75.6	1.00 (reference)	1.00 (reference)
GC	65	18.5	38	21.6	1.24 (0.79–1.94)	1.17 (0.71–2.14)	0.3574
CC	6	1.7	5	2.8	1.76 (0.53–5.87)	1.67 (0.45–6.17)	0.3515
Ptrendc							0.2150
Carrier comparison
GG+GC	346	98.3	171	97.2	1.00 (reference)	1.00 (reference)
CC	6	1.7	5	2.8	1.69 (0.51–5.60)	1.47 (0.42–4.78)	0.3888
GG	281	79.8	133	75.6	1.00 (reference)	1.00 (reference)
GC+CC	71	20.2	43	24.4	1.28 (0.83–1.97)	1.25 (0.74–1.84)	0.2619

Notes:

a Adjusted with age, gender, smoking, alcohol drinking, and areca chewing habits.

b Based on chi-squared test without Yates’ correction.

c Cochran–Armitage test was applied for the trend analysis. Bold values are statistically significant.

Abbreviations: IL-18, interleukin-18; NPC, nasopharyngeal carcinoma.

Table 3 Allelic frequency analysis for IL-18 polymorphisms and NPC

Allele	Controls, n (%)	Patients, n (%)	OR (95% CI)a	P-valueb
IL-18-656  G  T	418 (59.4) 286 (40.6)	208 (59.1) 144 (40.9)	1.00 (reference) 1.05 (0.84–1.23)	0.9294
IL-18-607  A  C	350 (49.7) 354 (50.3)	205 (58.2) 147 (41.8)	1.00 (reference) 0.77 (0.63–1.04)	0.0089*
IL-18-137  G  C	627 (89.1) 77 (10.9)	304 (86.4) 48 (13.6)	1.00 (reference) 1.15 (0.71–1.95)	0.2006

Notes:

a OR was adjusted with age, gender, smoking, alcohol drinking, and areca chewing.

b Based on chi-squared test without Yates’ correction. Bold values are statistically significant.

Abbreviations: IL-18, interleukin-18; NPC, nasopharyngeal carcinoma.

Table 4 OR for IL-18 promoter -607 genotype and NPC after stratified by smoking status

Genotypes	Nonsmokers		OR (95% CI)a	P-valueb	Smokers		OR (95% CI)a	P-valueb
	Controls	Cases			Controls	Cases
AA	46	36	1.00 (reference)		40	23	1.00 (reference)
AC	104	51	0.69 (0.42–1.02)	0.0947	74	36	0.81 (0.41–1.42)	0.6137
CC	52	16	0.37 (0.22–0.73)	0.0091	36	14	0.62 (0.33–1.37)	0.3385
Ptrendc				0.0080				0.3399

Notes:

a ORs were adjusted with age, gender, alcohol drinking, and areca chewing.

b Based on chi-squared test without Yates’ correction.

c Cochran–Armitage test was applied for the trend analysis. Bold values are statistically significant.

Abbreviations: IL-18, interleukin-18; NPC; nasopharyngeal carcinoma. Article 02: Untitled

Table 5 Summary of the characteristics of studies investigating IL-18-607 genotypes and NPC

Study	Year	Population	Ethnicity	Design	Sample size (case/control)	Matching criteria	Major findings	Reference
Huang et al (current study)	2018	Taiwan	Asian	Case–control	176/352	Age, gender	C allele is protective, especially for nonsmokers	–
Nong et al^Citation26	2009	China	Asian	Case–control	250/270	Age, gender	-607C alone is not protective, but -137C/-607A haplotype is risk	^Citation26
Farhat et al^Citation25	2008	Tunisia	African	Case–control	163/164	Age, gender	C allele has no effect	^Citation25
Pratesi et al^Citation24	2006	Italy	European	Case–control	89/130	Age, gender	C allele has no effect on risk, but on late stages	^Citation24

Abbreviations: IL-18, interleukin-18; NPC, nasopharyngeal carcinoma.

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