Analysis of 12 variants in the development of gastric and colorectal cancers

Table 1 Technical characteristics of the studied markers

Gene	ID	Type	Length, bp	Primers	Amplicon, bp
CASP8	rs3834129	INDEL	6	F-5’CTCTTCAATGCTTCCTTGAGGT3’	249-255
				R-5’CTGCATGCCAGGAGCTAAGTAT3’
CYP2E1	-	INDEL	96	F-5’TGTCCCAATACAGTCACCTCTTT3’	303-399
				R-5’GGCTTTTATTTGTTTTGCATCTG3’
CYP19A1	rs11575899	INDEL	3	F-5’TGCATGAGAAAGGCATCATATT3’	122-125
				R-5’AAAAGGCACATTCATAGACAAAAA3’
IL1A	rs3783553	INDEL	4	F-5’TGGTCCAAGTTGTGCTTATCC3’	230-234
				R-5’ACAGTGGTCTCATGGTTGTCA3’
IL4	rs79071878	VNTR	70	F-5’AGGGTCAGTCTGGCTACTGTGT3’	147/217/287
				R-5’CAAATCTGTTCACCTCAACTGC3’
MDM2	rs3730485	INDEL	40	F-5’GGAAGTTTCCTTTCTGGTAGGC3’	192-232
				R-5’TTTGATGCGGTCTCATAAATTG3’
NFKB1	rs28362491	INDEL	4	F-5’TATGGACCGCATGACTCTATCA3’	366-370
				R-5’GGCTCTGGCATCCTAGCAG3’
PAR1	rs11267092	INDEL	13	F-5’AAAACTGAACTTTGCCGGTGT3’	265-277
				R-5’GGGCCTAGAAGTCCAAATGAG3’
TP53	rs17878362	INDEL	16	F-5’GGGACTGACTTTCTGCTCTTGT3’	148-164
				R-5’GGGACTGTAGATGGGTGAAAAG3’
TYMS	rs16430	INDEL	6	F-5’ATCCAAACCAGAATACAGCACA3’	213-219
				R-5’CTCAAATCTGAGGGAGCTGAGT3’
UGT1A1	rs8175347	VNTR	2	F-5’CTCTGAAAGTGAACTCCCTGCT3’	133/135/137/139
				R-5’AGAGGTTCGCCCTCTCCTAT3’
XRCC1	rs3213239	INDEL	4	F-5’GAACCAGAATCCAAAAGTGACC3’	243-247
				R-5’AGGGGAAGAGAGAGAAGGAGAG3’

F: Forward; INDEL: Insertion/deletion; R: Reverse; VNTR: Variable number tandem repeat.

Table 2 Demographic data for patient and control groups

Variable	GC	CRC	Control	P-value
				GC vs Control	CRC vs Control
n	120	64	475	-	-
Age, yr1	57.02 ± 1.29	52.84 ± 1.90	55.59 ± 0.91	0.522	0.294
Sex, % of male/female	55.0/45.0	45.3/54.70	34.7/65.3	0.0003	0.098
European ancestry2	0.42 ± 0.01	0.53 ± 0.02	0.47 ± 0.01	0.0023	0.0033
African ancestry2	0.26 ± 0.01	0.20 ± 0.01	0.23 ± 0.01	0.071	0.0163
Amerindian ancestry2	0.32 ± 0.01	0.27 ± 0.02	0.30 ± 0.01	0.114	0.100

¹Values are expressed as mean ± SD. Significance was obtained by Student’s t-test;

²Values are expressed as mean ± SD. Significance was obtained by Mann-Whitney test;

³Statistically significant. CRC: Colorectal cancer; GC: Gastric cancer.

Table 3 Genotypic and allelic distributions of the investigated polymorphisms for patients with gastric cancer in comparison to control group

Genotype	GC	Control	P value1	OR (95%CI)1	Genotype	GC	Control	P value1	OR (95%CI)1
CASP8	120	475			RP2/RP2	18 (15.1)	154 (32.5)	0.189	0.673 (0.372-1.216)
DEL/DEL	11 (9.2)	90 (19.0)	0.650	0.892 (0.545-1.461)	Allele RP1	0.54	0.41
INS/DEL	70 (58.3)	230 (48.4)			Allele RP2	0.46	0.59
INS/INS	39 (32.5)	155 (32.6)	0.080	1.936 (0.924-4.058)	NFKB1	120	473
Allele DEL	0.38	0.43			DEL/DEL	34 (28.3)	117 (24.7)	0.0062	2.918 (1.352-6.298)
Allele INS	0.62	0.57			INS/DEL	71 (59.2)	246 (52.0)
MDM2	120	475			INS/INS	15 (12.5)	110 (23.3)	0.88	0.959 (0.5662-1.610)
DEL/DEL	13 (10.8)	33 (6.9)	0.199	1.365 (0.849-2.192)	Allele DEL	0.58	0.51
INS/DEL	46 (38.3)	168 (35.4)			Allele INS	0.42	0.49
INS/INS	61 (50.9)	274 (57.7)	0.0212	0.409 (0.192-0.872)	PAR1	113	473
Allele DEL	0.30	0.25			DEL/DEL	66 (58.4)	273 (57.7)	0.068	0.482 (0.221-1.054)
Allele INS	0.70	0.75			INS/DEL	36 (31.9)	169 (35.7)
TP53	120	475			INS/INS	11 (9.7)	31 (6.6)	0.949	0.984 (0.601-1.610)
DEL/DEL	91 (75.8)	350 (73.7)	0.999	138214253.0 (0.000)	Allele DEL	0.74	0.76
INS/DEL	27 (22.5)	116 (24.4)			Allele INS	0.26	0.24
INS/INS	2 (1.7)	9 (1.9)	0.247	0.708 (0.395-1.270)	CYP2E1	116	475
Allele DEL	0.87	0.86			DEL/DEL	94 (81.0)	398 (83.8)	0.999	276187721.0 (0.000)
Allele INS	0.13	0.14			INS/DEL	21 (18.1)	73 (15.4)
TYMS	120	475			INS/INS	1 (0.9)	4 (0.8)	0.574	1.193 (0.644-2.212)
DEL/DEL	16 (13.3)	65 (13.7)	0.409	1.231 (0.752-2.015)	Allele DEL	0.90	0.91
INS/DEL	53 (44.2)	224 (47.2)			Allele INS	0.10	0.09
INS/INS	51 (42.5)	186 (39.2)	0.867	1.060 (0.536-2.096)	CYP19A1	120	475
Allele DEL	0.35	0.37			DEL/DEL	18 (15.0)	76 (16.0)	0.654	1.127 (0.669-1.897)
Allele INS	0.65	0.63			INS/DEL	67 (55.8)	248 (52.2)
XRCC1	119	474			INS/INS	35 (29.2)	151 (31.8)	0.415	1.334 (0.667-2.671)
DEL/DEL	10 (8.4)	35 (7.4)	0.346	1.257 (0.781-2.021)	Allele DEL	0.43	0.42
INS/DEL	48 (40.3)	179 (37.8)			Allele INS	0.57	0.58
INS/INS	61 (51.3)	260 (54.8)	0.396	0.697 (0.303-1.604)	UGT1A1	120	464
Allele DEL	0.29	0.26			*1/*1	49 (40.8)	206 (44.5)	0.792	1.109 (0.515-2.386)
Allele INS	0.71	0.74			*1/*28	57 (47.5)	209 (45.0)
IL1A	120	475			*28/*28	12 (10.0)	46 (9.9)	0.445	1.205 (0.746-1.946)
DEL/DEL	17 (14.2)	86 (18.1)	0.626	0.882 (0.522-1.460)	*36/*1	2 (1.7)	3 (0.6)
INS/DEL	63 (52.5)	246 (51.8)			*36/*37	0 (0.0)	0 (0.0)	0.585	1.941 (0.180-20.973)
INS/INS	40 (33.3)	143 (30.1)	0.143	1.705 (0.835-3.482)	*1/*37	0 (0.0)	0 (0.0)
Allele DEL	0.40	0.44			Allele *36	0.01	0.01
Allele INS	0.60	0.56			Allele *1	0.65	0.67
IL4	119	474			Allele *28	0.34	0.32
RP1/RP1	28 (23.6)	69 (14.5)	0.0022	2.857 (1.490-5.479)	Allele *37	0.00	0.00
RP1/RP2	73 (61.3)	251 (53.0)

Data for GC and Control columns are presented as n or n (%).

¹Analysis of combined genotypes (INS/INS vs others, or DEL/DEL vs others) with adjusted values for confounding factors (sex and European ancestry) in logistic regression;

²Statistically significant. GC: Gastric cancer.

Table 4 Genotypic and allelic distributions of the investigated polymorphisms for patients with colorectal cancer in comparison to control group

Genotype	CRC	Control	P value1	OR (95%CI)a	Genotype	CRC	Control	P-value1	OR (95%CI)1
CASP8	63	475			RP2/RP2	16 (25.4)	154 (32.5)	0.871	1.068 (0.482-2.368)
DEL/DEL	13 (20.6)	90 (19.0)	0.676	0.888 (0.508-1.552)	Allele RP1	0.44	0.41
INS/DEL	28 (44.4)	230 (48.4)			Allele RP2	0.56	0.59
INS/INS	22 (35.0)	155 (32.6)	0.939	0.974 (0.503-1.887)	NFKB1	63	473
Allele DEL	0.43	0.43			DEL/DEL	16 (25.4)	117 (24.7)	0.0062	3.732 (1.451-9.599)
Allele INS	0.57	0.57			INS/DEL	42 (66.7)	246 (52.0)
MDM2	64	475			INS/INS	5 (7.9)	110 (23.3)	0.829	0.935 (0.508-1.723)
DEL/DEL	7 (10.9)	33 (6.9)	0.412	1.166 (0.143-9.487)	Allele DEL	0.60	0.51
INS/DEL	25 (39.1)	168 (35.4)			Allele INS	0.40	0.49
INS/INS	32 (50.0)	274 (57.7)	0.986	0.995 (0.546-1.811)	PAR1	63	473
Allele DEL	0.30	0.25			DEL/DEL	37 (58.7)	273 (57.7)	0.464	0.704 (0.275-1.801)
Allele INS	0.70	0.75			INS/DEL	20 (31.8)	169 (35.7)
TP53	64	475			INS/INS	6 (9.5)	31 (6.6)	0.813	0.937 (0.546-1.608)
DEL/DEL	47 (73.4)	350 (73.7)	0.886	1.166 (0.143-9.487)	Allele DEL	0.75	0.76
INS/DEL	16 (25.0)	116 (24.4)			Allele INS	0.25	0.24
INS/INS	1 (1.6)	9 (1.9)	0.986	0.995 (0.546-1.811)	CYP2E1	62	475
Allele DEL	0.86	0.86			DEL/DEL	56 (90.3)	398 (83.8)	0.999	189364591.0 (0.000)
Allele INS	0.14	0.14			INS/DEL	6 (9.7)	73 (15.4)
TYMS	63	475			INS/INS	0 (0.0)	4 (0.8)	0.351	0.655 (0.269-1.593)
DEL/DEL	11 (17.5)	65 (13.7)	0.304	1.342 (0.765-2.354)	Allele DEL	0.95	0.91
INS/DEL	31 (49.2)	224 (47.2)			Allele INS	0.05	0.09
INS/INS	21 (33.3)	186 (39.2)	0.429	0.751 (0.369-1.526)	CYP19A1	64	475
Allele DEL	0.42	0.37			DEL/DEL	7 (10.9)	76 (16.0)	0.297	0.747 (0.431-1.293)
Allele INS	0.58	0.63			INS/DEL	33 (51.6)	248 (52.2)
XRCC1	64	474			INS/INS	24 (37.5)	151 (31.8)	0.313	1.532 (0.669-3.508)
DEL/DEL	4 (6.2)	35 (7.4)	0.771	1.082 (0.637-1.838)	Allele DEL	0.37	0.42
INS/DEL	27 (42.2)	179 (37.8)			Allele INS	0.63	0.58
INS/INS	33 (51.6)	260 (54.8)	0.445	1.528 (0.515-4.535)	UGT1A1	63	464
Allele DEL	0.27	0.26			*1/*1	20 (31.7)	206 (44.5)	0.098	0.541 (0.262-1.120)
Allele INS	0.73	0.74			*1/*28	32 (50.8)	209 (45.0)
IL1A	64	475			*28/*28	6 (9.5)	46 (9.9)	0.370	1.282 (0.745-2.205)
DEL/DEL	10 (15.6)	86 (18.1)	0.657	0.880 (0.500-1.548)	*36/*1	3 (4.8)	3 (0.6)
INS/DEL	33 (51.6)	246 (51.8)			*36/*37	1 (1.6)	0 (0.0)	0.0012	12.849 (2.906-56.817)
INS/INS	21 (32.8)	143 (30.1)	0.610	1.208 (0.584-2.368)	*1/*37	1 (1.6)	0 (0.0)
Allele DEL	0.41	0.44			Allele *36	0.03	0.01
Allele INS	0.59	0.56			Allele *1	0.60	0.67
IL4	63	474			Allele *28	0.35	0.32
RP1/RP1	8 (12.7)	69 (14.5)	0.195	1.493 (0.814-2.740)	Allele *37	0.02	0.00
RP1/RP2	39 (61.9)	251 (53.0)

Data for CRC and Control columns are presented as n or n (%).

¹Analysis of combined genotypes (INS/INS vs others, or DEL/DEL vs others) with adjusted values for confounding factors (European and African ancestries) in logistic regression;

²Statistically significant. CRC: Colorectal cancer; INDEL: Insertion/deletion.