Lack of Association Between PDCD-1 Polymorphisms and Colorectal Cancer Risk: A Case-Control Study

Figures & data

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

Variable	Cases (n = 1,003)		Controls (n = 1,303)		P^a
	n	%	n	%
Age (years)	61.10 (±12.17)		61.40 (±9.61)		.496
Age (years)					.605
<61	451	44.97	600	46.05
≥61	552	55.03	703	53.95
Sex					.867
Male	620	61.81	801	61.47
Female	383	38.19	502	38.53
Smoking status					.002
Yes	744	74.18	1038	79.66
No	259	25.82	265	20.34
Alcohol use					<.001
Yes	829	82.65	1,167	89.56
No	174	17.35	136	10.44
BMI (kg/m2)
<24	670	66.80	688	52.80	<.001
≥24	333	33.20	615	47.20
Site of tumor
Colon cancer	431	42.97
Rectum cancer	572	57.03

Bold values are statistically significant (P < .05).

^aTwo-sided χ² test and Student t test.

Table 2. Data for PDCD-1 tagging SNPs

Genotyped SNPs	Chromosome	Chr Pos (NCBI Build 38)	Region	MAF^a for Chinese in database	MAF in our controls (n = 1.303)	P value for HWE^b test in our controls	Genotyping method	Genotyping value (%)
PDCD-1 rs10204525 T>C (1.6)	2	241850169	3’UTR	0.302	0.277	.293	SNPscan	98.92
PDCD-1 rs7421861 A>G (1.7)	2	241853198	Intron 1	0.165	0.164	.161	SNPscan	98.87
PDCD-1 rs2227982 A>G (1.9)	2	241851281	Exon 5	0.488	0.495	.827	SNPscan	98.87

MAF: minor allele frequency.

HWE: Hardy–Weinberg equilibrium.

Table 3. Logistic regression analyses of associations between PDCD-1 polymorphisms and the risk of CRC

Genotype	Cases (n = 1003)		Controls (n = 1303)		Crude OR (95%CI)	P	Adjusted OR ^a (95%CI)	P
	n	%	n	%
PDCD-1 rs10204525 T>C
TT	509	51.89	688	52.92	1.00		1.00
TC	387	39.45	505	38.85	1.04(.87–1.23)	.694	1.03(.86–1.23)	.754
CC	85	8.66	107	8.23	1.07(.79–1.46)	.649	1.10(.81–1.51)	.535
TC+CC	472	48.11	612	47.08	1.04(.88–1.23)	.623	1.04(.88–1.23)	.635
TT+TC	896	91.34	1,193	91.77	1.00		1.00
CC	85	8.66	107	8.23	1.06(.79–1.43)	.711	1.09(.81–1.48)	.575
C allele	557	28.39	719	27.65
PDCD-1 rs7421861 A>G
AA	691	70.51	915	70.38	1.00		1.00
AG	260	26.53	343	26.38	1.00(.83–1.21)	.969	1.00(.83–1.22)	.968
GG	29	2.96	42	3.23	0.92(.56–1.48)	.718	0.93(.57–1.52)	.767
AG+GG	289	29.49	385	29.62	0.99(.83–1.19)	.948	1.00(.83–1.20)	.965
AA+AG	951	97.04	1,258	96.77	1.00		1.00
GG	29	2.96	42	3.23	0.91(.57–1.48)	.714	0.93(.57–1.51)	.762
G allele	318	16.22	427	16.42
PDCD-1 rs2227982 A>G
AA	254	25.92	333	25.62	1.00		1.00
AG	495	50.51	646	49.69	1.01(.82–1.23)	.964	1.03(.84–1.26)	.813
GG	231	23.57	321	24.69	0.94(.75–1.19)	.628	0.96(.76–1.22)	.736
AG+GG	726	74.08	967	74.38	0.98(.81–1.19)	.870	1.00(.83–1.22)	.974
AA+AG	749	76.43	979	75.31	1.00		1.00
GG	231	23.57	321	24.69	0.94(.78–1.14)	.537	0.94(.78–1.15)	.568
G allele	957	48.83	1,288	49.54

Adjusted for age, sex, BMI, smoking, and drinking status.

Table 4. Stratified analyses between PDCD-1.6 polymorphism and CRC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	PDCD-1.6 (rs10204525 T>C) (case/control) ^a			Adjusted OR ^b (95% CI); P
	TT	TC	CC	Additive model	Homozygote model	Dominant model	Recessive model
Sex
Male	315/418	247/316	43/65	1.04(.83–1.31); P: .707	0.91(.60–1.38); P: .652	1.02(.82–1.27); P: .847	0.89(.59–1.34); P: .578
Female	194/270	140/189	42/42	0.98(.73–1.32); P: .902	1.41(.88–2.28); P: .153	1.06(.81–1.39); P: .685	1.43(.90–2.26); P: .131
Age
<61	200/291	166/201	33/48	1.24(.95–1.62); P: .119	1.03(.65–1.64); P: .890	1.20(.93–1.54); P: .164	0.94(.60–1.48); P: .796
≥61	309/397	221/304	52/59	0.89(.70–1.14); P: .357	1.19(.78–1.82); P: .430	0.94(.75–1.18); P: .583	1.25(.82–1.89); P: .297
Smoking status
Never	382/541	279/407	68/87	0.97(.79–1.19); P: .753	1.13(.80–1.60); P: .501	1.00(.82–1.21); P: .964	1.14(.82–1.60); P: .438
Ever	127/147	108/98	17/20	1.26(.87–1.83); P: .215	1.03(.51–2.09)	1.23(.86–1.74); P: .259	0.93(.47–1.85)
					P: .925		P:.843
Alcohol consumption
Never	415/606	323/456	73/102	1.00(.83–1.22); P: .968	1.03(.74–1.43); P: .860	1.01(.84–1.21); P: .926	1.03(.75–1.41); P: .864
Ever	94/82	64/49	12/5	1.20(.74–1.95); P: .469	2.15(.71–6.46)	1.29(.81–2.05); P: .292	2.00(.68–5.92)
					P: .175		P: .211
BMI(kg/m^2)
<24	337/349	263/282	57/55	0.99(.79–1.25); P: .945	1.11(.74–1.66); P: .612	1.01(.81–1.26); P: .920	1.11(.76–1.64); P: .588
≥24	172/339	124/223	28/52	1.09(.82–1.45); P: .564	1.11(.68–1.83)	1.09(.83–1.44); P: .522	1.07(.66–1.74)
					P: .676		P: .772

The genotyping was successful in 981(97.81%) cases, and 1,300 (99.77%) controls for PDCD-1 .6.

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

Table 5. Stratified analyses between PDCD-1.7 polymorphism and CRC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	PDCD-1.7 (rs7421861 A>G) (case/control) ^a			Adjusted OR ^b (95% CI); P
	AA	AG	GG	Additive model	Homozygote model	Dominant model	Recessive model
Sex
Male	436/544	152/225	16/30	0.85(.67–1.09); P: .203	0.65(.34–1.21); P: .175	0.83(.65–1.05); P: .117	0.68(.36–1.26); P: .220
Female	255/371	108/118	13/12	1.28(.94–1.75); P: .122	1.72(.76–3.90); P: .192	1.32(.98–1.78); P: .072	1.61(.72–3.64); P: .249
Age
<60	280/386	107/140	12/14	1.15(.86–1.53); P: .344	1.22(.56–2.62); P: .617	1.16(.88–1.52); P: .308	1.17(.55–2.52); P: .684
≥60	411/529	153/203	17/28	0.90(.69–1.17); P: .431	0.74(.39–1.41); P: .360	0.88(.69–1.13); P: .321	0.76(.40–1.45); P: .405
Smoking status
Never	507/733	201/269	20/33	1.07(.86–1.34); P: .524	0.92(.52–1.63); P: .766	1.06(.86–1.30); P: .607	0.90(.51–1.59); P: .714
Ever	184/182	59/74	9/9	0.79(.53–1.19); P: .265	0.96(.37–2.51); P: .938	0.81(.55–1.20); P: .294	1.03(.40–2.66); P: .959
Alcohol consumption
Never	562/818	225/307	23/39	1.04(.85–1.28); P: .682	0.86(.51–1.47); P: .582	1.02(.84–1.25); P: .817	0.85(.50–1.45); P: .550
Ever	129/97	35/36	6/3	0.75(.44–1.29); P: .304	1.50(.36–6.25); P: .578	0.81(.48–1.36); P: .429	1.61(.39–6.67); P: .513
BMI(kg/m^2)
<24	458/476	179/189	19/21	1.01(.79–1.29); P: .937	0.96(.50–1.81); P: .888	1.00(.79–1.27); P: .970	0.95(.51–1.80); P: .881
≥24	233/439	81/154	10/21	0.99(.72–1.35); P: .927	0.92(.42–2.00); P: .832	0.98(.72–1.32); P: .882	0.92(.43–2.00); P: .839

The genotyping was successful in 980(97.71%) cases, and 1,300 (99.77%) controls for PDCD-1.7.

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

Table 6. Stratified analyses between PDCD-1.9 polymorphism and CRC risk by sex, age, BMI, smoking status, and alcohol consumption

Variable	PDCD-1.9 (rs2227982 A>G) (case/control) ^a			Adjusted OR ^b (95% CI); P
	AA	AG	GG	Additive model	Homozygote model	Dominant model	Recessive model
Sex
Male	158/199	305/392	141/208	1.00(.77–1.31); P: .975	0.87(.64–1.18); P: .373	0.96(.75–1.23); P: .733	0.87(.68–1.12); P: .268
Female	96/134	190/254	90/113	1.08(.77–1.50); P: .665	1.14(.77–1.68); P: .522	1.09(.80–1.49); P: .571	1.08(.78–1.50); P: .631
Age
<60	96/137	215/271	88/132	1.16(.85–1.58); P: .342	0.99(.69–1.43); P: .967	1.11(.83–1.48); P: .501	0.90(.67–1.21); P: .477
≥60	15	280/375	143/189	0.94(.71–1.24); P: .645	0.93(.68–1.28); P: .665	0.94(.72–1.21); P: .613	0.97(.75–1.27); P: .833
Smoking status
Never	191/269	365/507	172/259	1.05(.83–1.32); P: .710	0.96(.74–1.27); P: .791	1.02(.82–1.27); P: .876	0.94(.75–1.17); P: .567
Ever	63/64	130/139	59/62	0.96(.63–1.48); P: .863	0.96(.58–1.60); P: .883	0.96(.64–1.45); P: .855	0.99(.65–1.50); P: .954
Alcohol consumption
Never	204/288	413/584	193/292	1.00(.80–1.24); P: .975	0.93(.72–1.20); P: .568	0.97(.79–1.20); P: .801	0.93(.75–1.15); P: .499
Ever	50/45	82/62	38/29	1.34(.78–2.29); P: .289	1.20(.64–2.28); P: .571	1.29(.79–2.12); P: .315	1.01(.58–1.77); P: .960
BMI(kg/m^2)
<24	165/180	334/332	157/174	1.14(.87–1.48); P: .344	1.02(.75–1.38); P: .920	1.09(.85–1.40); P: .477	0.93(.73–1.20); P: .592
≥24	89/153	161/314	74/147	0.89(.64–1.23); P: .461	0.90(.61–1.32); P: .579	0.89(.65–1.21); P: .450	0.97(.70–1.34); P: .861

The genotyping was successful in 980(97.71%) cases, and 1,300 (99.77%) controls for PDCD-1 .9.

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

Figure 1. Linkage disequilibrium correlations among different loci.

Table 7. Combination analysis of PDCD-1 polymorphisms in CRC patients and controls

Genotype	Case (n = 1,960)		Control (n = 2,600)		OR (95% CI)	P-value
	n	%	n	%
T A A	1,001	51.07	1,305	50.19	1.00
T G A	394	20.10	570	21.92	0.90(.77–1.05)	.181
C G G	310	15.82	420	16.15	0.96(.81–1.14)	.654
C G A	247	12.60	296	11.38	1.09(.90–1.31)	.380
T G G	6	0.31	2	0.07	3.91(.79–19.43)	.072
Others	2	0.10	6	0.23	0.43(.09–2.16)	.294