Leukocyte DNA methylation and colorectal cancer among male smokers

doi:10.4251/wjgo.v4.i8.193

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastrointest Oncol. Aug 15, 2012; 4(8): 193-201
Published online Aug 15, 2012. doi: 10.4251/wjgo.v4.i8.193

Table 1 Characteristics of cases and controls n (%)

	Controls (n = 219)	Cases (n = 221)	P¹
Age of randomization (mean) (yr)	58 (54-62)	58 (54-61)	0.7
ATBC			0.33
Placebo	62 (28)	48 (22)
Β-carotene	56 (26)	60 (27)
VitE	49 (22)	62 (28)
Both	52 (24)	51 (23)
Family history of CRC	6 (3)	6 (3)	0.98
Smoking age (mean) (yr)	20 (17-22)	19 (17-20)	0.18
Smoking years (mean) (yr)	36 (30-42)	37 (31-42)	0.26
BMI (kg/m²)			0.03
< 25	80 (36)	75 (34)
25-29.9	113 (52)	99 (45)
≥ 30	26 (12)	47 (21)

¹P from T-test for continuous variables or χ² test for categorical variables. CRC: Colorectal cancer; ATBC: α-tocopherol, β-carotene; BMI: Body mass index.

Table 2 Methylation of CpG sites associated with colorectal cancer development (P value < 0.01 before multiple testing correction)¹

Marker name	2nd tertile vs 1st tertile			3rd tertile vs 1st tertile			P²
	OR	L95	U95	OR	L95	U95
DSP	1.09876	0.95772	1.26057	1.26539	1.11734	1.43306	0.000599826
MLH3	1.04349	0.90638	1.20134	1.26606	1.0994	1.45798	0.000731318
FLT4	1.25952	1.10631	1.43394	1.14513	0.98989	1.32473	0.00096231
INSR	1.16236	1.01962	1.32509	1.24011	1.09317	1.40681	0.001490452
GLA	1.37049	1.15665	1.62388	1.44612	1.19452	1.75072	0.001636963
PTCH2	1.18022	1.03475	1.34615	1.26374	1.11417	1.43339	0.001637435
GSTM2	1.24321	1.09656	1.40947	1.17084	1.02674	1.33516	0.001994473
HCK	1.18573	1.04409	1.34659	1.19691	1.03199	1.38819	0.002287131
PLAGL1	0.91619	0.80363	1.04451	0.87645	0.75745	1.01414	0.002326078
PARP1	1.07016	0.95	1.20553	0.86663	0.75535	0.9943	0.003005978
COL18A1	1.23987	1.08901	1.41162	1.20014	1.05351	1.36719	0.003163099
KCNK4	1.19498	1.05273	1.35645	1.15065	1.00785	1.31368	0.003250103
GJB2	1.16605	1.02831	1.32224	1.02785	0.89877	1.17547	0.003317356
SEMA3F	1.16703	1.01753	1.33848	1.16456	1.01456	1.33673	0.00380004
HBII	0.89709	0.79121	1.01713	0.86969	0.7624	0.99207	0.004064919
SEMA3C	1.08773	0.96383	1.22756	0.87597	0.76919	0.99757	0.004352617
MME_	1.18426	1.04194	1.34601	1.17187	1.02959	1.3338	0.005258668
WNT1_	1.18575	1.02807	1.36761	1.07102	0.91035	1.26004	0.005648004
SGCE	1.0712	0.93671	1.22501	1.22832	1.08144	1.39516	0.00629186
PDE1B_	1.24257	1.09182	1.41413	1.21384	1.04623	1.40831	0.008629968
HIC1	1.16348	1.01124	1.33864	1.22483	1.06765	1.40515	0.008997589
PODXL	1.16034	1.02143	1.31815	1.12456	0.98675	1.2816	0.009182736
IL18BP	1.17737	1.0254	1.35188	1.07299	0.91441	1.25908	0.009206805
DKC1	1.05822	0.92046	1.2166	1.22886	1.05463	1.43187	0.009315729
B3GALT5	0.95137	0.83621	1.08239	1.20365	1.05804	1.3693	0.009772808
SNRPN	0.85441	0.7514	0.97155	0.98115	0.86779	1.1093	0.00995797

¹The markers detected here could be markers indicating susceptibility;

²P from logistic regression model (all cases were included).

Table 3 Methylation of CpG sites related to colorectal cancer development with different latencies (P value < 0.01 before multiple testing correction)¹

Marker name	2nd tertile vs 1st tertile			3rd tertile vs 1st tertile			P²
	OR	L95	U95	OR	L95	U95
DSP	1.52027	0.91054	2.53831	2.62423	1.65105	4.17103	0.000104474
PTCH2	1.86565	1.14946	3.02807	2.55851	1.60114	4.08832	0.000327688
GLA	3.22896	1.66054	6.27879	3.62345	1.70627	7.69478	0.000529374
FLT4	2.49882	1.55051	4.02713	1.7312	1.02958	2.91095	0.000651567
B3GALT5	0.91735	0.5746	1.46454	2.11128	1.31709	3.38434	0.000726807
INSR	1.88977	1.16281	3.07122	2.44371	1.52713	3.91043	0.0007899
GSTM2	2.29464	1.44903	3.63373	1.92103	1.18011	3.12712	0.001165928
FASTK	1.66117	1.02457	2.69331	2.26999	1.43313	3.59553	0.001992703
MLH3	1.12063	0.67503	1.86036	2.15187	1.31098	3.53213	0.002175877
HOXC6	1.2189	0.75795	1.96015	2.06861	1.32056	3.24043	0.002826542
MGMT	2.42747	1.34114	4.39373	2.71599	1.45027	5.08638	0.00448402
SYBL1	1.35661	0.89446	2.05754	0.63927	0.39971	1.02239	0.004618893
PDE1B	2.12203	1.33959	3.36151	1.74663	1.01704	2.9996	0.004839975
SEMA3C	1.34045	0.87915	2.04378	0.62126	0.38566	1.0008	0.004858838
AFF3	2.11473	1.30773	3.41973	1.88147	1.16588	3.03628	0.005422481
HCK	2.0406	1.27766	3.25911	2.0338	1.19416	3.46382	0.005503
PXN	1.92122	1.24421	2.9666	1.12493	0.66824	1.89374	0.005766585
PARP1	1.19708	0.79209	1.80913	0.55056	0.33191	0.91323	0.006004429
TK1	1.83172	1.07512	3.12075	2.24792	1.34064	3.76922	0.006184503
SGCE	1.21217	0.74619	1.96916	1.9685	1.25257	3.09363	0.006354949
MME	2.00858	1.25423	3.21663	1.94042	1.20308	3.12967	0.00664085
RARA	1.51526	0.94405	2.43209	2.07639	1.31635	3.27525	0.006899358
COL18A1	2.08647	1.28893	3.37752	1.90316	1.17926	3.07144	0.007110996
SEMA3F	1.98588	1.21715	3.24014	2.03976	1.22672	3.39166	0.007292652
ITGB4	2.08685	1.2669	3.43748	2.02919	1.20223	3.42495	0.007595246
PTPRH	0.47922	0.30082	0.76343	0.71909	0.44823	1.15361	0.007598903
SMO	1.52188	0.95276	2.43094	2.08604	1.3032	3.33915	0.008280298
DKC1	1.25326	0.76383	2.05632	2.20393	1.27785	3.80116	0.008427231
TRPM5	2.22962	1.33245	3.73087	1.80604	1.01389	3.21707	0.008971559
EVI1	1.62829	1.01415	2.61431	2.08373	1.29638	3.34927	0.009481166
EPHA3	1.93252	1.21576	3.07185	1.85827	1.15814	2.98165	0.009792546

¹Latency: according to the time difference between blood draw and cancer diagnosis, cases were classified to three categories-short, medium, and long latency;

²P from proportional odds regression model (all cases were included).

Table 4 Methylation of CpG sites associated with colorectal cancer with short to mediate latency (P value < 0.01 before multiple testing correction)¹

Marker name	2nd tertile vs 1st tertile			3rd tertile vs 1st tertile			P²
	OR	L95	U95	OR	L95	U95
GLA	1.31618	1.12303	1.54256	1.31082	1.09072	1.57534	0.000126734
DSP	1.12406	0.9868	1.2804	1.25115	1.11146	1.4084	0.000305565
B3GALT5	1.00109	0.88664	1.1303	1.18931	1.05066	1.34625	0.001334159
MLH3	1.01719	0.89178	1.16025	1.2404	1.08916	1.41263	0.001421327
PTCH2	1.18044	1.04387	1.33487	1.24209	1.1026	1.39922	0.002140961
FLT4	1.26038	1.1159	1.42356	1.15518	1.01153	1.31924	0.002164413
SGCE	1.05149	0.92678	1.19299	1.19126	1.05786	1.34148	0.002535873
HOXC6	1.02303	0.90426	1.15741	1.16253	1.03342	1.30777	0.002602644
PDE1B	1.19845	1.06385	1.35009	1.10584	0.96046	1.27323	0.002706305
COL18A1	1.2126	1.07142	1.37239	1.19961	1.06058	1.35687	0.002968143
TRPM5	1.16951	1.02324	1.3367	1.10173	0.94879	1.27933	0.003084609
EVI1	1.06179	0.93967	1.19979	0.94512	0.8274	1.07959	0.003902443
GSTM2	1.24009	1.10312	1.39407	1.13952	1.0059	1.29089	0.003956314
FASTK	1.12763	0.99513	1.27778	1.17539	1.04318	1.32436	0.004798386
PARP1	1.08475	0.97053	1.2124	0.87907	0.77119	1.00203	0.005028903
PTGS2	1.03008	0.91145	1.16415	1.15319	1.02574	1.29648	0.00571389
WRN	0.97839	0.8614	1.11128	1.09867	0.96629	1.24918	0.005779497
EPO	1.14731	1.01334	1.299	1.13034	0.9854	1.2966	0.006090622
GPC3	1.19056	1.03981	1.36316	1.09698	0.94341	1.27556	0.006093671
TK1	1.13458	0.98846	1.30232	1.20862	1.05753	1.3813	0.006272625
EVI1	1.14882	1.01559	1.29953	1.17851	1.04142	1.33364	0.006474115
EPHB2	1.15596	1.02875	1.2989	1.05233	0.92701	1.19459	0.006504075
SEMA3C	1.10197	0.98427	1.23375	0.89579	0.7921	1.01304	0.00677389
HLA_DPA1	1.14664	1.00965	1.30223	1.09326	0.95971	1.24538	0.006960326
SYBL1	1.06835	0.9547	1.19553	0.90635	0.80226	1.02394	0.007029222
INSR	1.19021	1.05214	1.34639	1.25474	1.11332	1.41412	0.008045993

¹The logistic regression analysis only includes cases with short and medium latency;

²P from proportional odds regression model (all cases were included).

Citation: Gao Y, Killian K, Zhang H, Yu K, Li QZ, Weinstein S, Virtamo J, Tucker M, Taylor P, Albanes D, Meltzer P, Caporaso N. Leukocyte DNA methylation and colorectal cancer among male smokers. World J Gastrointest Oncol 2012; 4(8): 193-201
URL: https://www.wjgnet.com/1948-5204/full/v4/i8/193.htm
DOI: https://dx.doi.org/10.4251/wjgo.v4.i8.193