Lethal-7-related polymorphisms are associated with susceptibility to and prognosis of gastric cancer

Table 1 General characteristics of subjects included in this study

	Cases	Controls	P value
n	898	992
Gender
Male	649 (72.3)	714 (72.0)	0.886
Female	249 (27.7)	278 (28.0)
Age (yr)	61.1 ± 11.4	59.2 ± 10.0	< 0.001
≤ 65	582 (64.8)	703 (70.9)	0.005
> 65	316 (35.2)	289 (29.1)
Helicobacter pylori
Negative	290 (32.5)	505 (50.9)	< 0.001
Positive	603 (67.5)	487 (49.1)

Table 2 The genotype distribution between gastric cancer cases and controls

Gene	SNP	Genotypes	Cases	Controls	P valuea	OR (95% CI)b
let-7a-1	rs13293512	T/T	270 (30.3)	310 (31.5)	0.593	1.00
		T/C	442 (49.6)	494 (50.2)		1.03 (0.83-1.28)
		C/C	180 (20.2)	181 (18.4)		1.13 (0.86-1.48)
let-7a-2	rs562052	G/G	382 (43.0)	439 (44.3)	0.814	1.00
		G/A	413 (46.5)	446 (45.0)		1.06 (0.87-1.29)
		A/A	94 (10.6)	106 (10.7)		0.96 (0.70-1.32)
let-7a-2	rs547008	C/C	529 (59.2)	575 (58.3)	0.875	1.00
		C/T	321 (35.9)	358 (36.3)		0.96 (0.79-1.17)
		T/T	44 (4.9)	53 (5.4)		0.85 (0.56-1.30)
let-7a-2	rs1143770	T/T	255 (28.9)	282 (28.7)	0.262	1.00
		T/C	456 (51.8)	482 (49.0)		1.04 (0.83-1.29)
		C/C	170 (19.3)	219 (22.3)		0.83 (0.64-1.09)
let-7a-2	rs629367	A/A	532 (59.2)	597 (60.3)	0.583	1.00
		A/C	323 (36.0)	355 (35.9)		1.01 (0.83-1.22)
		C/C	43 (4.8)	38 (3.8)		1.21 (0.76-1.92)
let-7i	rs10877887	T/T	370 (42.3)	406 (42.2)	0.777	1.00
		T/C	399 (45.6)	449 (46.7)		0.96 (0.78-1.17)
		C/C	106 (12.1)	107 (11.1)		1.04 (0.76-1.42)
LIN28A	rs3811463	T/T	672 (74.8)	689 (69.5)	0.024	1.00
		T/C	203 (22.6)	265 (26.7)		0.76 (0.61-0.94)
		C/C	23 (2.6)	38 (3.8)		0.59 (0.34-1.01)
	Dominant	T/T	672 (74.8)	689 (69.5)	0.009	1.00
		T/C+C/C	226 (25.2)	303 (30.5)		0.74 (0.60-0.91)
IL23R	rs10889677	A/A	476 (53.2)	545 (55.2)	0.685	1.00
		A/C	356 (39.8)	375 (38.0)		1.10 (0.91-1.34)
		C/C	63 (7.0)	68 (6.9)		1.07 (0.74-1.55)
RAD52	rs7963551	T/T	597 (66.6)	672 (68.0)	0.666	1.00
		T/G	267 (29.8)	287 (29.0)		1.06 (0.87-1.31)
		G/G	32 (3.6)	29 (2.9)		1.18 (0.69-2.01)
KRAS	rs712	G/G	540 (61.0)	589 (60.5)	0.646	1.00
		G/T	296 (33.4)	339 (34.8)		0.94 (0.77-1.15)
		T/T	49 (5.5)	46 (4.7)		1.14 (0.74-1.75)

^aP was computed using the χ² test.

^bORs with 95%CIs were computed using a logistic model after adjusting for age, gender, and Helicobacter pylori status.

SNP: Single nucleotide polymorphism; ORs: Odds ratios; CIs: Confidence intervals.

Table 3 Multivariate stepwise logistic regression analysis of gastric cancer risk

Factor	OR	95%CI	P value
rs3811463 (each increase in C allele)	0.74	0.61-0.88	0.001
Helicobacter pylori (positive vs negative)	2.20	1.81-2.67	< 0.001
Age (> 65 vs ≤ 65 yr)	1.31	1.07-1.61	0.010

OR: Odds ratio; CI: Confidence interval.

Table 4 Genotypes of single nucleotide polymorphisms and overall survival of gastric cancer patients

SNP	Genotype	Total	Death (%)	5-yr survival rate	Median survival time	P valuea
rs13293512	T/T	213	100 (46.9)	51.6%	85.2	0.508
	T/C	370	172 (46.5)	53.3%	75.8
	C/C	148	60 (40.5)	59.0%	-b
rs562052	G/G	313	150 (47.9)	51.5%	76.2	0.253
	G/A	337	141 (41.8)	56.9%	-b
	A/A	77	40 (51.9)	50.7%	65.4
rs547008	C/C	434	200 (46.1)	53.0%	85.2	0.148
	C/T	264	112 (42.4)	56.2%	-b
	T/T	34	21 (61.8)	46.7%	33.8
rs1143770	T/T	215	98 (45.6)	54.3%	-b	0.535
	T/C	370	164 (44.3)	54.4%	-b
	C/C	138	68 (49.3)	51.3%	65.4
rs629367	A/A	435	205 (47.1)	52.8%	75.8	0.834
	A/C	264	113 (42.8)	55.6%	-b
	C/C	36	16 (44.4)	55.8%	85.2
rs10877887	T/T	301	147 (48.8)	50.4%	64.7	0.235
	T/C	330	141 (42.7)	57.2%	-b
	C/C	88	39 (44.3)	53.7%	-b
rs3811463	T/T	555	251 (45.2)	53.7%	85.2	0.971
	T/C	162	75 (46.3)	54.9%	77.7
	C/C	18	8 (44.4)	52.0%	-b
rs10889677	A/A	379	158 (41.7)	57.7%	-b	0.049
	A/C	301	146 (48.5)	50.3%	65.4
	C/C	53	30 (56.6)	46.0%	41.0
rs7963551	T/T	508	236 (46.5)	52.56%	85.2	0.144
	T/G	199	82 (41.2)	59.35%	-b
	G/G	27	16 (59.3)	38.22%	41.3
rs712	G/G	452	215 (47.6)	51.51%	73.7	0.227
	G/T	235	95 (40.4)	58.64%	-b
	T/T	36	17 (47.2)	55.01%	77.7

^aP was computed by log-rank test.

^bMedian survival time could not be estimated as fewer than 50% of patients died.

Table 5 Associations between clinical factors and overall survival of gastric cancer patients

Variable	Classification	na	Death (%)	5-yr survival (%)	P valueb
Age (yr)	≤ 65	494	197 (39.9)	59.7 (55.0-64.0)	< 0.001
	> 65	241	137 (56.8)	42.3 (35.6-48.8)
Gender	Female	195	82 (42.1)	56.8 (49.2-63.7)	0.261
	Male	540	252 (46.7)	52.9 (48.4-57.2)
Differentiation	Poor	508	241 (47.4)	50.9 (46.2-55.3)	0.010
	Moderate and high	209	85 (40.7)	61.6 (54.4-68.0)
WHO type	Tubular adenocarcinoma	614	275 (44.8)	54.8 (50.6-58.8)	0.205
	Signet ring cell	72	32 (44.4)	52.8 (39.8-64.2)
	Other	45	25 (55.6)	44.5 (29.2-58.6)
T stage	T1	100	13 (13.0)	85.8 (76.5-91.6)	< 0.001
	T2	102	16 (15.7)	84.4 (74.8-90.6)
	T3	423	220 (52.0)	48.1 (43.1-52.9)
	T4	103	78 (75.7)	17.4 (9.2-27.8)
N stage	N0	219	38 (17.4)	84.2 (78.4-88.5)	< 0.001
	N1	184	63 (34.2)	66.0 (58.2-72.6)
	N2	150	87 (58.0)	38.7 (30.3-47.1)
	N3	175	139 (79.4)	17.3 (11.7-23.9)
TNM	I	137	12 (8.8)	90.6 (83.9-94.6)	< 0.001
	II	278	92 (33.1)	68.3 (62.1-73.6)
	III	313	223 (71.2)	25.8 (20.7-31.2)
Lymphovascular invasion	Negative	213	38 (17.8)	83.0 (77.0-87.6)	< 0.001
	Positive	511	287 (56.2)	42.6 (38.1-47.0)
Neural invasion	Negative	328	100 (30.5)	70.2 (64.6-75.0)	< 0.001
	Positive	396	225 (56.8)	41.1 (36.0-46.2)
Chemotherapy	No	488	218 (44.7)	54.8 (50.0-59.3)	0.054
	FOLFOX-4	136	63 (46.3)	52.1 (43.2-60.3)
	XELOX	73	28 (38.4)	61.7 (49.1-72.0)
	Other	38	25 (65.8)	34.0 (19.1-49.4)
Helicobacter pylori	Negative	228	109 (47.8)	49.8 (42.7-56.4)	0.364
	Positive	503	222 (44.1)	56.1 (51.4-60.4)

^aSome of the variables have missing values (The missing number was 4 for the variable of WHO type, 18 for differentiation, 7 for T stage, 7 for N stage, 7 for TNM stage, 11 for lymphovascular invasion, 11 for neural invasion, and 4 for Helicobacter pylori, respectively).

^bP was computed by log-rank test.

Table 6 Multivariate Cox regression analysis of gastric cancer survival

Variable	Comparison	HR	95%CI	P value
rs10889677	each increase in C allele	1.25	1.05-1.49	0.012
Age (yr)	> 65 vs ≤ 65	1.39	1.10-1.75	0.005
TNM stage	II vs I	3.49	1.88-6.48	< 0.001
	III vs I	11.12	6.00-20.61	< 0.001
Lymphovascular invasion	Positive vs Negative	1.89	1.32-2.72	0.001
Chemotherapy	Yes vs No	0.74	0.59-0.95	0.016

HR: Hazard ratio; CI: Confidence interval.