Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non-small-cell lung cancer: a case–control study in Eastern Chinese Han population

Figures & data

Table 1 Distribution of selected demographic variables and risk factors in NSCLC cases and controls

Variables	Overall cases (n=521)	Overall controls (n=1,030)	P-valuea
	n (%)	n (%)
Age (years)	59.76±10.71	60.34±9.11	0.268
Age (years)			0.843
<60	238 (45.68)	476 (46.21)
≥60	283 (54.32)	554 (53.79)
Sex			0.453
Male	287 (55.09)	588 (57.09)
Female	234 (44.91)	442 (42.91)
Smoking status			<0.001
Never	317 (60.84)	828 (80.39)
Ever	204 (39.16)	202 (19.61)
Alcohol use			<0.001
Never	444 (85.22)	949 (92.14)
Ever	77 (14.78)	81 (7.86)
BMI (kg/m^2)	23.00±3.03	23.84±3.06	<0.001
BMI (kg/m^2)
<24	337 (64.68)	547 (53.11)	<0.001
≥24	184 (35.32)	483 (46.89)
Lymph node status
Positive	200 (38.39)
Negative	314 (60.27)
Unknown	7 (1.34)
TNM stage
I+II	315 (60.46)
I+IV	206 (39.54)
Type of NSCLC
Adenocarcinoma	415 (79.65)
Squamous cell carcinoma	85 (16.31)
Others	21 (4.03)

Notes: Bold values are statistically significant (P<0.05).

a Two-sided chi-squared test and Student’s t-test.

Abbreviations: BMI, body mass index; NSCLC, non-small-cell lung cancer; TNM, tumor-lymph node-metastasis.

Table 2 Primary information for IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A polymorphisms

Genotyped SNPs	Chromosome	Chr Pos (NCBI Build 38)	MAF for Chinese in database	MAF in our controls (n=1,030)	P-value for HWE test in our controls	Genotyping method	Genotyping value (%)
IGF2BP2 rs1470579 A>C	3	185811292	0.27	0.25	0.001	SNPscan	99.94
IGF2BP2 rs4402960 G>T	3	185793899	0.26	0.25	0.001	SNPscan	99.94
IGFBP3 rs2270628 C>T	7	45909971	0.21	0.19	0.672	SNPscan	99.94
IGFBP3 rs3110697 G>A	7	45915430	0.23	0.26	0.102	SNPscan	99.94
IGFBP3 rs6953668 G>A	7	45916276	0.04	0.05	0.565	SNPscan	99.87

Abbreviations: MAF, minor allele frequency; HWE, Hardy–Weinberg equilibrium; SNP, single-nucleotide polymorphism.

Table 3 The frequencies of IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A and rs6953668 G>A polymorphisms in different NSCLC subgroups

Genotype	NSCLC cases (n=521)		Adenocarcinoma (n=415)		Non-adenocarcinoma (n=106)		Controls (n=1,030)
	n	%	n	%	n	%	n	%
IGF2BP2 rs1470579 A>C
AA	302	58.54	241	58.07	61	57.55	593	57.63
AC	187	35.89	148	35.66	39	36.79	350	34.01
CC	32	6.14	26	6.27	6	5.66	86	8.36
C allele	251	24.09	200	24.10	51	24.06	522	25.36
IGF2BP2 rs4402960 G>T
GG	306	58.73	244	58.80	62	58.49	603	58.60
GT	185	35.51	146	35.18	39	36.79	344	33.43
TT	30	5.76	25	6.03	5	4.72	82	7.97
T allele	245	23.51	196	23.61	49	23.11	508	24.68
IGFBP3 rs2270628 C>T
CC	334	64.11	273	65.78	61	57.55	670	65.11
CT	163	31.29	122	29.40	41	38.68	318	30.90
TT	24	4.61	20	4.82	4	3.77	41	3.98
T allele	211	20.25	162	19.52	49	23.11	400	19.44
IGFBP3 rs3110697 G>A
GG	286	54.89	235	56.63	51	48.11	578	56.17
GA	190	36.47	142	34.22	48	45.28	373	36.25
AA	45	8.64	38	9.16	7	6.60	78	7.58
A allele	280	26.87	218	26.27	62	29.25	529	25.70
IGFBP3 rs6953668 G>A
GG	466	89.44	375	90.36	91	85.85	920	89.49
GA	53	10.17	39	9.40	14	13.21	104	10.12
AA	2	0.38	1	0.24	1	0.94	4	0.39
A allele	57	5.47	41	4.94	16	7.55	112	5.45

Abbreviation: NSCLC, non-small-cell lung cancer.

Table 4 Logistic regression analyses of association of IGF2BP2 rs1470579 A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A polymorphisms with risk of NSCLC

Genotype	Overall NSCLC cases (n=521) vs controls (n=1,030)				Adenocarcinoma (n=415) vs controls (n=1,030)				Non-adenocarcinoma (n=106) vs controls (n=1,030)
	Crude OR (95% CI)	P-value	Adjusted ORa (95% CI)	P-value	Crude OR (95% CI)	P-value	Adjusted ORa (95% CI)	P-value	Crude OR (95% CI)	P-value	Adjusted ORa (95% CI)	P-value
IGF2BP2 rs1470579 A>C
Additive model	1.05 (0.84–1.32)	0.666	1.03 (0.82–1.30)	0.800	1.04 (0.82–1.33)	0.739	1.03 (0.80–1.33)	0.805	1.09 (0.71–1.66)	0.705	1.04 (0.65–1.66)	0.859
Homozygote model	0.73 (0.48–1.12)	0.154	0.72 (0.46–1.12)	0.143	0.75 (0.47–1.19)	0.214	0.73 (0.46–1.18)	0.200	0.68 (0.29–1.62)	0.383	0.67 (0.26–1.70)	0.393
Dominant model	0.99 (0.80–1.22)	0.899	0.97 (0.78–1.21)	0.775	0.98 (0.78–1.24)	0.877	0.97 (0.77–1.23)	0.814	1.00 (0.67–1.50)	0.987	0.97 (0.62–1.52)	0.893
Recessive model	0.72 (0.47–1.09)	0.122	0.71 (0.46–1.10)	0.121	0.73 (0.47–1.15)	0.180	0.73 (0.46–1.15)	0.174	0.66 (0.28–1.54)	0.336	0.65 (0.26–1.64)	0.364
IGF2BP2 rs4402960 G>T
Additive model	1.06 (0.85–1.33)	0.604	1.03 (0.82–1.30)	0.801	1.05 (0.82–1.34)	0.692	1.03 (0.80–1.33)	0.802	1.10 (0.72–1.68)	0.644	1.03 (0.65–1.65)	0.889
Homozygote model	0.72 (0.47–1.12)	0.147	0.72 (0.46–1.14)	0.162	0.76 (0.47–1.21)	0.243	0.75 (0.47–1.22)	0.251	0.59 (0.23–1.52)	0.278	0.60 (0.22–1.65)	0.324
Dominant model	1.00 (0.80–1.23)	0.960	0.97 (0.78–1.21)	0.797	0.99 (0.79–1.25)	0.946	0.98 (0.77–1.24)	0.857	1.01 (0.67–1.51)	0.983	0.96 (0.61–1.49)	0.840
Recessive model	0.71 (0.46–1.09)	0.114	0.71 (0.46–1.12)	0.139	0.74 (0.47–1.18)	0.203	0.75 (0.46–1.20)	0.222	0.57 (0.23–1.44)	0.237	0.59 (0.22–1.60)	0.303
IGFBP3 rs2270628 C>T
Additive model	1.03 (0.82–1.30)	0.803	1.01 (0.79–1.28)	0.945	0.94 (0.73–1.21)	0.647	0.92 (0.71–1.19)	0.504	1.42 (0.93–2.15)	0.101	1.43 (0.90–2.27)	0.127
Homozygote model	1.18 (0.70–1.98)	0.542	1.13 (0.66–1.95)	0.648	1.20 (0.69–2.08)	0.520	1.19 (0.68–2.09)	0.550	1.07 (0.37–3.10)	0.896	1.11 (0.35–3.52)	0.857
Dominant model	1.05 (0.84–1.30)	0.695	1.02 (0.81–1.29)	0.852	0.97 (0.76–1.23)	0.809	0.95 (0.74–1.21)	0.658	1.38 (0.92–2.07)	0.123	1.40 (0.89–2.18)	0.145
Recessive model	1.16 (0.70–1.95)	0.564	1.13 (0.66–1.93)	0.654	1.22 (0.71–2.11)	0.476	1.22 (0.70–2.14)	0.485	0.95 (0.33–2.69)	0.916	0.97 (0.31–3.04)	0.963
IGFBP3 rs3110697 G>A
Additive model	1.03 (0.82–1.29)	0.789	1.02 (0.80–1.28)	0.902	0.94 (0.73–1.20)	0.609	0.93 (0.72–1.19)	0.549	1.46 (0.97–2.21)	0.073	1.53 (0.97–2.43)	0.068
Homozygote model	1.17 (0.79–1.73)	0.439	1.18 (0.79–1.79)	0.420	1.20 (0.79–1.82)	0.390	1.21 (0.79–1.85)	0.388	1.02 (0.45–2.32)	0.965	0.89 (0.36–2.19)	0.805
Dominant model	1.05 (0.85–1.30)	0.632	1.04 (0.84–1.30)	0.712	0.98 (0.78–1.24)	0.875	0.97 (0.77–1.23)	0.820	1.38 (0.93–2.06)	0.113	1.41 (0.91–2.19)	0.129
Recessive model	1.15 (0.79–1.69)	0.467	1.18 (0.79–1.75)	0.426	1.23 (0.82–1.84)	0.319	1.24 (0.82–1.89)	0.306	0.86 (0.39–1.92)	0.716	0.74 (0.31–1.77)	0.501
IGFBP3 rs6953668 G>A
Additive model	1.01 (0.71–1.43)	0.963	1.05 (0.73–1.51)	0.808	0.92 (0.63–1.36)	0.681	0.94 (0.63–1.40)	0.772	1.36 (0.75–2.48)	0.309	1.45 (0.74–2.83)	0.277
Homozygote model	0.99 (0.18–5.42)	0.990	0.60 (0.11–3.40)	0.562	0.62 (0.07–5.52)	0.664	0.48 (0.05–4.40)	0.519	2.53 (0.28–22.91)	0.408	1.32 (0.13–13.49)	0.816
Dominant model	1.01 (0.71–1.42)	0.980	1.02 (0.71–1.46)	0.908	0.91 (0.62–1.33)	0.623	0.92 (0.62–1.36)	0.679	1.40 (0.79–2.51)	0.253	1.44 (0.75–2.76)	0.272
Recessive model	0.99 (0.18–5.40)	0.988	0.60 (0.11–3.38)	0.559	0.62 (0.07–5.55)	0.668	0.49 (0.05–4.42)	0.522	2.44 (0.27–22.02)	0.427	1.26 (0.12–12.93)	0.844

Note:

a Adjusted for age, sex, smoking status, alcohol use, and BMI status.

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 5 Stratified analyses between IGF2BP2 rs1470579 A>C polymorphism and NSCLC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	IGF2BP2 rs1470579 A>C (case/control)a			Adjusted ORb (95% CI); P
	AA	AC	CC	AA	AC	CC	AC/CC	CC vs (AC/AA)
Sex
Male	165/344	101/198	21/45	1.00	1.05 (0.76–1.45); 0.789	1.00 (0.55–1.81); 0.999	1.04 (0.76–1.41); 0.824	0.98 (0.55–1.76); 0.953
Female	137/249	86/152	11/41	1.00	1.01 (0.72–1.43); 0.935	0.46 (0.23–0.94); 0.032	0.90 (0.65–1.24); 0.506	0.46 (0.23–0.92); 0.028
Age
<60	148/273	82/159	8/43	1.00	0.94 (0.66–1.33); 0.725	0.36 (0.16–0.80); 0.012	0.82 (0.59–1.14); 0.237	0.37 (0.17–0.81); 0.013
≥60	154/320	105/191	24/43	1.00	1.12 (0.82–1.54); 0.479	1.08 (0.62–1.89); 0.787	1.11 (0.83–1.51); 0.481	1.03 (0.60–1.78); 0.909
Smoking status
Never	185/471	113/284	19/72	1.00	1.00 (0.76–1.33); 0.978	0.64 (0.37–1.11); 0.111	0.93 (0.71–1.21); 0.585	0.64 (0.38–1.09); 0.102
Ever	117/122	74/66	13/14	1.00	1.12 (0.73–1.70); 0.610	0.89 (0.40–1.99); 0.771	1.08 (0.72–1.61); 0.720	0.85 (0.39–1.87); 0.688
Alcohol consumption
Never	259/548	161/318	24/82	1.00	1.09 (0.85–1.40); 0.510	0.61 (0.37–0.99); 0.046	0.99 (0.78–1.25); 0.908	0.59 (0.36–0.95); 0.031
Ever	43/45	26/32	8/4	1.00	0.76 (0.38–1.51); 0.427	2.23 (0.58–8.50); 0.242	0.90 (0.47–1.72); 0.740	2.51 (0.68–9.25); 0.168
BMI (kg/m^2)
<24	189/303	125/191	23/52	1.00	1.03 (0.76–1.39); 0.842	0.69 (0.40–1.19); 0.183	0.96 (0.72–1.27); 0.760	0.68 (0.40–1.16); 0.158
≥24	113/290	62/159	9/34	1.00	1.04 (0.72–1.52); 0.823	0.78 (0.35–1.70); 0.526	1.00 (0.70–1.43); 0.996	0.76 (0.35–1.65); 0.494

Notes:

a For IGF2BP2 rs1470579 A>C, the genotyping was successful in 521 (100.00%) NSCLC cases and 1,029 (99.90%) controls.

b Adjusted for multiple comparisons (age, sex, BMI, smoking status, and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model. Bold values are statistically significant (P<0.05).

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 6 Stratified analyses between IGF2BP2 rs4402960 G>T polymorphism and NSCLC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	IGF2BP2 rs4402960 G>T (case/control)a			Adjusted ORb (95% CI); P
	GG	GT	TT	GG	GT	TT	GT/TT	TT vs (GT/GG)
Sex
Male	168/349	99/195	20/43	1.00	1.02 (0.74–1.41); 0.905	1.04 (0.57–1.90); 0.902	1.02 (0.75–1.39); 0.893	1.03 (0.57–1.86); 0.922
Female	138/254	86/149	10/39	1.00	1.03 (0.73–1.46); 0.852	0.46 (0.21–0.93); 0.031	0.91 (0.66–1.26); 0.574	0.44 (0.21–0.91); 0.026
Age (years)
<60	147/277	82/158	9/40	1.00	0.96 (0.68–1.36); 0.817	0.44 (0.20–0.95); 0.037	0.86 (0.61–1.20); 0.361	0.45 (0.21–0.96); 0.038
≥60	159/326	103/186	21/42	1.00	1.10 (0.80–1.52); 0.555	0.99 (0.56–1.77); 0.975	1.08 (0.80–1.46); 0.615	0.96 (0.54–1.68); 0.875
Smoking status
Never	188/480	111/278	18/69	1.00	1.00 (0.76–1.33); 0.979	0.64 (0.37–1.12); 0.117	0.93 (0.71–1.22); 0.593	0.64 (0.37–1.10); 0.109
Ever	118/123	74/66	12/13	1.00	1.12 (0.73–1.70); 0.608	0.91 (0.40–2.09); 0.823	1.08 (0.73–1.62); 0.698	0.87 (0.39–1.98); 0.744
Alcohol consumption
Never	263/555	157/314	24/79	1.00	1.06 (0.83–1.36); 0.647	0.62 (0.38–1.02); 0.061	0.97 (0.76–1.23); 0.801	0.61 (0.37–0.99); 0.046
Ever	43/48	28/30	6/3	1.00	0.92 (0.46–1.82); 0.802	2.73 (0.58–12.72); 0.202	1.05 (0.54–2.02); 0.895	2.83 (0.62–12.84); 0.179
BMI (kg/m^2)
<24	194/306	121/192	22/48	1.00	0.96 (0.71–1.30); 0.780	0.71 (0.41–1.24); 0.232	0.91 (0.68–1.21); 0.507	0.72 (0.42–1.25); 0.244
≥24	112/297	64/152	8/34	1.00	1.17 (0.80–1.71); 0.413	0.73 (0.32–1.64); 0.442	1.09 (0.76–1.57); 0.628	0.69 (0.31–1.54); 0.361

Notes:

a For IGF2BP2 rs4402960 G>T, the genotyping was successful in 521 (100.00%) NSCLC cases and 1,029 (99.90%) controls.

b Adjusted for multiple comparisons (age, sex, BMI, smoking status and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model. Bold values are statistically significant (P<0.05).

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 7 Stratified analyses between IGFBP3 rs2270628 C>T polymorphism and NSCLC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	IGFBP3 rs2270628 C>T (case/control)a			Adjusted ORb (95% CI); P
	CC	CT	TT	CC	CT	TT	CT/TT	TT vs (CT/CC)
Sex
Male	188/382	84/183	15/22	1.00	0.91 (0.65–1.27); 0.573	1.39 (0.67–2.88); 0.376	0.96 (0.70–1.32); 0.794	1.43 (0.70–2.94); 0.332
Female	146/288	79/135	9/19	1.00	1.11 (0.79–1.57); 0.554	0.96 (0.42–2.20); 0.920	1.09 (0.78–1.53); 0.605	0.93 (0.41–2.10); 0.854
Age (years)
<60	155/309	71/152	12/14	1.00	0.94 (0.66–1.34); 0.735	1.90 (0.81–4.47); 0.139	1.01 (0.72–1.43); 0.940	1.94 (0.83–4.51); 0.125
≥60	179/361	92/166	12/27	1.00	1.06 (0.77–1.47); 0.725	0.87 (0.42–1.79); 0.695	1.03 (0.76–1.41); 0.841	0.85 (0.41–1.74); 0.654
Smoking status
Never	201/541	103/252	13/34	1.00	1.07 (0.80–1.42); 0.656	0.98 (0.50–1.92); 0.946	1.06 (0.80–1.39); 0.704	0.96 (0.49–1.86); 0.893
Ever	133/129	60/66	11/7	1.00	0.88 (0.57–1.35); 0.561	1.53 (0.57–4.08); 0.399	0.94 (0.63–1.42); 0.783	1.59 (0.60–4.21); 0.352
Alcohol consumption
Never	283/623	139/287	22/38	1.00	1.07 (0.83–1.38); 0.594	1.18 (0.67–2.08); 0.560	1.08 (0.85–1.38); 0.515	1.16 (0.66–2.02); 0.611
Ever	51/47	24/31	2/3	1.00	0.68 (0.34–1.35); 0.268	0.78 (0.12–5.26); 0.802	0.69 (0.35–1.34); 0.269	0.90 (0.14–5.91); 0.909
BMI (kg/m^2)
<24	210/353	107/171	20/22	1.00	1.08 (0.79–1.47); 0.642	1.58 (0.82–3.05); 0.171	1.13 (0.84–1.52); 0.407	1.54 (0.81–2.95); 0.190
≥24	124/317	56/147	4/19	1.00	0.92 (0.63–1.35); 0.670	0.54 (0.18–1.66); 0.285	0.88 (0.60–1.28); 0.493	0.56 (0.18–1.69); 0.303

Notes:

a For IGFBP3 rs2270628 C>T, the genotyping was successful in 521 (100%) NSCLC cases and 1,029 (99.90%) controls.

b Adjusted for multiple comparisons (age, sex, BMI, smoking status, and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model.

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 8 Stratified analyses between IGFBP3 rs3110697 G>A polymorphism and NSCLC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	IGFBP3 rs3110697 G>A (case/control)a			Adjusted ORb (95% CI); P
	GG	GA	AA	GG	GA	AA	GA/AA	AA vs (GA/GG)
Sex
Male	155/332	109/208	23/47	1.00	1.10 (0.80–1.52); 0.571	1.00 (0.56–1.76); 0.986	1.08 (0.79–1.46); 0.634	0.96 (0.55–1.67); 0.879
Female	131/246	81/165	22/31	1.00	0.92 (0.65–1.30); 0.640	1.45 (0.80–2.63); 0.224	1.00 (0.72–1.39); 0.994	1.50 (0.84–2.67); 0.175
Age (years)
<60	129/274	89/163	20/38	1.00	1.14 (0.81–1.62); 0.450	1.18 (0.64–2.18); 0.591	1.15 (0.83–1.60); 0.408	1.12 (0.62–2.03); 0.709
≥60	157/304	101/210	25/40	1.00	0.93 (0.67–1.28); 0.642	1.18 (0.67–2.06); 0.566	0.97 (0.72–1.31); 0.831	1.21 (0.70–2.09); 0.485
Smoking status
Never	175/472	112/295	30/60	1.00	1.03 (0.78–1.37); 0.835	1.43 (0.88–2.32); 0.146	1.10 (0.84–1.43); 0.506	1.41 (0.88–2.26); 0.149
Ever	111/106	78/78	15/18	1.00	0.98 (0.65–1.48); 0.920	0.79 (0.38–1.65); 0.527	0.94 (0.64–1.40); 0.767	0.79 (0.39–1.63); 0.531
Alcohol consumption
Never	243/538	163/339	38/71	1.00	1.07 (0.83–1.37); 0.621	1.26 (0.82–1.96); 0.295	1.10 (0.87–1.39); 0.441	1.23 (0.80–1.89); 0.339
Ever	43/40	27/34	7/7	1.00	0.69 (0.34–1.38); 0.294	0.80 (0.25–2.54); 0.709	0.71 (0.37–1.37); 0.306	0.94 (0.31–2.86); 0.913
BMI (kg/m^2)
<24	194/321	118/184	25/41	1.00	1.00 (0.74–1.35); 0.999	0.71 (0.57–1.74); 0.995	1.00 (0.75–1.33); 0.993	1.00 (0.58–1.72); 0.998
≥24	92/257	72/189	20/37	1.00	1.01 (0.70–1.47); 0.960	1.47 (0.80–2.72); 0.217	1.09 (0.76–1.54); 0.647	1.47 (0.81–2.65); 0.206

Notes:

a For IGFBP3 rs3110697 G>A, the genotyping was successful in 521 (100%) NSCLC cases and 1,029 (99.90%) controls.

b Adjusted for multiple comparisons (age, sex, BMI, smoking status, and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model.

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 9 Stratified analyses between IGFBP3 rs6953668 G>A polymorphism and NSCLC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	IGFBP3 rs6953668 G>A (case/control)a			Adjusted ORb (95% CI); P
	GG	GA	AA	GG	GA	AA	GA/AA	AA vs (GA/GG)
Sex
Male	254/523	31/60	2/3	1.00	1.14 (0.70–1.87); 0.593	0.63 (0.10–3.91); 0.623	1.10 (0.68–1.78); 0.700	0.63 (0.10–3.86); 0.613
Female	212/397	22/44	0/1	1.00	0.94 (0.54–1.61); 0.811	–	0.92 (0.53–1.58); 0.754	–
Age (years)
<60	217/429	21/43	0/2	1.00	1.02 (0.57–1.80); 0.960	–	0.96 (0.54–1.69); 0.877	–
≥60	249/491	32/61	2/2	1.00	1.07 (0.66–1.71); 0.791	0.97 (0.13–7.16); 0.974	1.06 (0.67–1.69); 0.802	0.96 (0.13–7.11); 0.969
Smoking status
Never	281/741	36/84	0/1	1.00	1.17 (0.76–1.79); 0.474	–	1.15 (0.75–1.76); 0.519	–
Ever	185/179	17/20	2/3	1.00	0.81 (0.41–1.60); 0.534	0.66 (0.11–4.07); 0.655	0.79 (0.41–1.50); 0.468	0.68 (0.11–4.16); 0.672
Alcohol consumption
Never	399/848	44/96	1/3	1.00	1.03 (0.69–1.52); 0.897	0.47 (0.05–4.64); 0.514	1.00 (0.68–1.47); 0.998	0.46 (0.05–4.63); 0.513
Ever	67/72	9/8	1/1	1.00	1.16 (0.41–3.26); 0.778	0.82 (0.05–13.69); 0.888	1.12 (0.42–3.00); 0.823	0.80 (0.05–13.34); 0.876
BMI (kg/m^2)
<24	301/486	34/60	2/0	1.00	0.96 (0.61–1.52); 0.862	–	1.00 (0.64–1.58); 0.991	–
≥24	165/434	19/44	0/4	1.00	1.18 (0.65–2.13); 0.584	–	1.03 (0.57–1.84); 0.930	–

Notes:

a For IGFBP3 rs6953668 G>A, the genotyping was successful in 521 (100%) NSCLC cases and 1,028 (99.81%) controls.

b Adjusted for multiple comparisons (age, sex, BMI, smoking status, and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model.

Abbreviations: NSCLC, non-small-cell lung cancer; BMI, body mass index.

Table 10 IGF2BP2 and IGFBP3 haplotype frequencies (%) in patients and controls and risk of NSCLC

Haplotypes	Cases (n=1042)		Controls (n=2,060)		Crude OR (95% CI)	P-value
	n	%	n	%
Ars1470579Crs2270628Grs3110697Grs4402960Grs6953668	444	42.65	888	43.21	Reference	–
Ars1470579Crs2270628Ars3110697Grs4402960Grs6953668	150	14.41	282	13.72	1.06 (0.85–1.34)	0.596
Crs1470579Crs2270628Grs3110697Trs4402960Grs6953668	133	12.78	304	14.79	0.88 (0.69–1.11)	0.262
Ars1470579Trs2270628Grs3110697Grs4402960Grs6953668	137	13.16	225	12.41	1.22 (0.96–1.55)	0.109
Crs1470579Crs2270628Ars3110697Trs4402960Grs6953668	47	4.51	83	4.04	1.13 (0.78–1.65)	0.516
Crs1470579Trs2270628Grs3110697Trs4402960Grs6953668	43	4.13	74	3.60	1.16 (0.78–1.72)	0.453
Ars1470579Crs2270628Ars3110697Grs4402960Ars6953668	34	3.27	56	2.73	1.21 (0.78–1.89)	0.388
Ars1470579Trs2270628Ars3110697Grs4402960Grs6953668	16	1.54	50	2.43	0.64 (0.36–1.14)	0.125
Crs1470579Crs2270628Ars3110697Trs4402960Ars6953668	12	1.15	15	0.73	1.60 (0.74–3.45)	0.226
Ars1470579Trs2270628Ars3110697Grs4402960Ars6953668	6	0.58	12	0.58	1.00 (0.37–2.68)	1.000
Crs1470579Trs2270628Ars3110697Trs4402960Grs6953668	4	0.38	11	0.54	0.73 (0.23–2.30)	0.785
Crs1470579Crs2270628Grs3110697Grs4402960Grs6953668	5	0.48	7	0.34	1.43 (0.45–4.53)	0.549
Crs1470579Trs2270628Ars3110697Trs4402960Ars6953668	3	0.29	9	0.44	0.67 (0.18–2.48)	0.761
Crs1470579Crs2270628Ars3110697Grs4402960Grs6953668	2	0.19	3	0.15	1.33 (0.22–8.01)	1.000
Ars1470579Crs2270628Ars3110697Trs4402960Grs6953668	3	0.29	2	0.10	3.00 (0.50–18.03)	0.341
Ars1470579Crs2270628Grs3110697Grs4402960Ars6953668	0	0.00	13	0.63	–	0.007
Crs1470579Trs2270628Grs3110697Grs4402960Grs6953668	0	0.00	8	0.39	–	0.058
Ars1470579Trs2270628Grs3110697Grs4402960Ars6953668	0	0.00	3	0.15	–	0.555
Crs1470579Trs2270628Grs3110697Trs4402960Ars6953668	0	0.00	3	0.15	–	0.555
Others	2	0.19	7	0.34	0.57 (0.12–2.76)	0.726

Note: Bold values are statistically significant (P<0.05).

Abbreviation: NSCLC, non-small-cell lung cancer.