Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 2, Number 6, December 2009, pages 311-316

No Association of Obesity and Type 2 Diabetes Mellitus Related Genetic Variants With Colon Cancer

**Table 1.** Descriptive Characteristics of Kentucky Colon Cancer Study Population
	Cases (N = 561)	Controls (N = 721)	p*
Univariate (t-test or chi-square) p-value for association with colon cancer. For family history, type 2 diabetes diagnosis and NSAID use, this is a test of difference in positive vs. negative responses between cases and controls, ignoring unknown or missing data. *Self-reported physician diagnosis of type 2 diabetes ^†Regular non-steroidal anti-inflammatory drug (NSAID) use was defined as reporting ever use of NSAIDs at least twice a week for at least six months. ‡Family history of colorectal cancer.
Gender – N (%)			< 0.001
Male	266 (47.3)	274 (38.0)
Female	295 (52.7)	447 (61.0)
Mean (stddev) age	62.8 (10.7)	58.3 (10.9)	< 0.001
Race – N (%)			0.24
African-American	27 (4.8)	23 (3.2)
Caucasian	526 (93.8)	678 (94.0)
Other	8 (1.4)	15 (2.1)
Unknown	0 (0)	5 (0.7)
Body Mass Index (kg/m²)	29.3 (6.1)	28.3 (6.2)	0.0077
Diabetes Diagnosis (%)**			0.019
Yes	105 (18.7)	105 (14.6)
No	397 (70.8)	568 (78.8)
Unknown	59 (10.5)	48 (6.7)
Family History‡			0.0014
Yes	94 (16.8)	72 (10.0)
No	297 (52.9)	395 (54.8)
Unknown	170 (30.3)	254 (35.2)
Regular NSAID Use^†			0.16
Yes	235 (41.9)	306 (42.4)
No	131 (23.4)	138 (19.1)
Unknown	195 (38.8)	277 (38.4)
HHEX – rs1111875			0.13
CC	217 (38.7)	241 (33.4)
CT	255 (45.5)	348 (48.3)
TT	88 (15.7)	131 (18.2)
No call	1 (0.2)	1 (0.1)
KCNJ11-rs5219			0.39
CC	226 (40.3)	304 (42.2)
CT	265 (47.2)	316 (43.8)
TT	68 (12.1)	100 (13.9)
No call	2 (0.4)	1 (0.1)
rs9300039			0.73
AA	9 (1.6)	8 (1.1)
AC	103 (18.4)	136 (18.9)
CC	448 (79.9)	576 (79.9)
No call	1 (0.2)	1 (0.1)
SLC30A8 – rs1326634			0.48
CC	274 (48.9)	329 (45.6)
CT	230 (41.0)	319 (44.2)
TT	55 (9.8)	71 (9.9)
No call	2 (0.4)	2 (0.3)
FTO-rs9939609 AA			0.66
AA	90 (16.0)	121 (16.8)
AT	252 (44.9)	336 (46.6)
TT	217 (38.7)	261 (36.2)
No call	2 (0.4)	3 (0.4)
FTO-rs8050136			0.74
AA	91 (16.2)	119 (16.5)
AC	250 (44.6)	336 (46.6)
CC	217 (38.7)	265 (36.8)
No call	3 (0.5)	1 (0.1)
CDKN2 – rs10811661			0.34
CC	21 (3.7)	19 (2.6)
CT	142 (25.3)	202 (28.0)
TT	395 (70.4)	500 (69.4)
No call	3 (0.5)	0 (0)
CDKAL1 – rs7754840			0.75
GG	241 (43.0)	325 (45.1)
CG	254 (45.3)	313 (43.4)
CC	64 (11.4)	81 (11.2)
No call	2 (0.4)	2 (0.3)
TCF2 – rs4430796			0.81
AA	141 (25.1)	178 (24.7)
AG	297 (52.9)	374 (51.9)
GG	122 (21.7)	168 (23.3)
No call	1 (0.2)	1 (0.1)

Table 1. Descriptive Characteristics of Kentucky Colon Cancer Study Population

Cases (N = 561)

Controls (N = 721)

*Univariate (t-test or chi-square) p-value for association with colon cancer. For family history, type 2 diabetes diagnosis and NSAID use, this is a test of difference in positive vs. negative responses between cases and controls, ignoring unknown or missing data. **Self-reported physician diagnosis of type 2 diabetes ^†Regular non-steroidal anti-inflammatory drug (NSAID) use was defined as reporting ever use of NSAIDs at least twice a week for at least six months. ‡Family history of colorectal cancer.

Gender – N (%)

< 0.001

Male

266 (47.3)

274 (38.0)

Female

295 (52.7)

447 (61.0)

Mean (stddev) age

62.8 (10.7)

58.3 (10.9)

< 0.001

Race – N (%)

0.24

African-American

27 (4.8)

23 (3.2)

Caucasian

526 (93.8)

678 (94.0)

Other

8 (1.4)

15 (2.1)

Unknown

0 (0)

5 (0.7)

Body Mass Index (kg/m²)

29.3 (6.1)

28.3 (6.2)

0.0077

Diabetes Diagnosis (%)**

0.019

Yes

105 (18.7)

105 (14.6)

397 (70.8)

568 (78.8)

Unknown

59 (10.5)

48 (6.7)

Family History‡

0.0014

Yes

94 (16.8)

72 (10.0)

297 (52.9)

395 (54.8)

Unknown

170 (30.3)

254 (35.2)

Regular NSAID Use^†

0.16

Yes

235 (41.9)

306 (42.4)

131 (23.4)

138 (19.1)

Unknown

195 (38.8)

277 (38.4)

HHEX – rs1111875

0.13

217 (38.7)

241 (33.4)

255 (45.5)

348 (48.3)

88 (15.7)

131 (18.2)

No call

1 (0.2)

1 (0.1)

KCNJ11-rs5219

0.39

226 (40.3)

304 (42.2)

265 (47.2)

316 (43.8)

68 (12.1)

100 (13.9)

No call

2 (0.4)

1 (0.1)

rs9300039

0.73

9 (1.6)

8 (1.1)

103 (18.4)

136 (18.9)

448 (79.9)

576 (79.9)

No call

1 (0.2)

1 (0.1)

SLC30A8 – rs1326634

0.48

274 (48.9)

329 (45.6)

230 (41.0)

319 (44.2)

55 (9.8)

71 (9.9)

No call

2 (0.4)

2 (0.3)

FTO-rs9939609
AA

0.66

90 (16.0)

121 (16.8)

252 (44.9)

336 (46.6)

217 (38.7)

261 (36.2)

No call

2 (0.4)

3 (0.4)

FTO-rs8050136

0.74

91 (16.2)

119 (16.5)

250 (44.6)

336 (46.6)

217 (38.7)

265 (36.8)

No call

3 (0.5)

1 (0.1)

CDKN2 – rs10811661

0.34

21 (3.7)

19 (2.6)

142 (25.3)

202 (28.0)

395 (70.4)

500 (69.4)

No call

3 (0.5)

0 (0)

CDKAL1 – rs7754840

0.75

241 (43.0)

325 (45.1)

254 (45.3)

313 (43.4)

64 (11.4)

81 (11.2)

No call

2 (0.4)

2 (0.3)

TCF2 – rs4430796

0.81

141 (25.1)

178 (24.7)

297 (52.9)

374 (51.9)

122 (21.7)

168 (23.3)

No call

1 (0.2)

1 (0.1)

**Table 2.** Descriptive Characteristics of Kentucky Colon Cancer Study Population
Gene	SNP	Base Model*	Full Model†
*Logistic regression controlling for age, sex and race (558 cases and 698 controls). †Logistic regression controlling for age, sex, race, family history of colorectal cancer, non-steroidal anti-inflammatory. drug (NSAID) use and body mass index (BMI) (503 cases and 670 controls with complete data). ‡p-value of additive, dominant or recessive genetic model.
HHEX	rs1111875
CC	217/241	1.0 (ref)	0.20	1.0 (ref)	0.22
CT	255/348	0.80 (0.62 - 1.03)		0.79 (0.60 - 1.03)
TT	88/131	0.85 (0.60 - 1.19)		0.87 (0.61- 1.24)
TT vs. CC/CT		0.97 (0.52 - 3.10)	0.84	1.00 (0.72 - 1.37)	0.98
CT/TT vs. CC		0.81 (0.64 - 1.03)	0.089	0.81 (0.63 - 1.04)	0.097
KCNJ11	rs5219
CC	226/304	1.0 (ref)	0.93	1.0 (ref)	0.32
CT	265/316	1.15 (0.90 - 1.47)		1.20 (0.92 - 1.56)
TT	68/100	0.92 (0.63 - 1.32)		0.98 (0.67 - 1.56)
TT vs. CC/CT		0.85 (0.60 - 1.20)	0.35	0.89 (0.62 - 1.27)	0.89
CT/TT vs. CC		1.10 (0.87 - 1.39)	0.44	1.15 (0.90 - 1.47)	0.28
—	rs9300039
CC	448/576	1.0 (ref)	0.64	1.0 (ref)	0.85
AC	103/136	1.04 (0.78 - 1.41)		1.03 (0.75 - 1.41)
AA	9/8	1.28 (0.48 - 3.45)		1.35 (0.46 - 3.95)
AA vs. CC/CA		1.28 (0.47 - 3.47)	0.63	1.35 (0.46 - 3.92)	0.59
AC/AA vs. CC		1.06 (0.79 - 1.41)	0.71	1.05 (0.77 - 1.42)	0.77
SLC30A8	rs13266634
CC	274/329	1.0 (ref)	0.60	1.0 (ref)	0.61
CT	230/319	0.92 (0.72 - 1.18)		0.88 (0.68 - 1.14)
TT	55/71	0.94 (0.63 - 1.41)		0.99 (0.65 - 1.51)
TT vs. CC/CT		0.98 (0.67 - 1.44)	0.94	1.05 (0.70 - 1.57)	0.81
CT/TT vs. CC		0.93 (0.74 - 1.17)	0.52	0.90 (0.71 - 1.15)	0.40
FTO	rs9939609
TT	217/261	1.0 (ref)	0.35	1.0 (ref)	0.40
AT	252/336	0.90 (0.69 - 1.15)		0.84 (0.65 - 1.10)
AA	90/121	0.86 (0.62 - 1.22)		0.84 (0.58 - 1.19)
AA vs. TT/AT vs. AA		0.88 (0.70 - 1.12)	0.54	0.92 (0.66 - 1.27)	0.61
AT/AA vs. TT		0.92 (0.67 - 1.25)	0.32	0.84 (0.65 - 1.08)	0.17
FTO	rs8050136
CC	217/261	1.0 (ref)	0.42	1.0 (ref)	0.48
AC	250/336	0.90 (0.70 - 1.16)		0.85 (0.65 - 1.11)
AA	91/119	0.89 (0.64 - 1.25)		0.87 (0.61 - 1.11)
AA vs. CC/AC		0.90 (0.71 - 1.14)	0.72	0.86 (0.67 - 1.83)	0.23
AC/AA vs. CC		0.95 (0.70 - 1.29)	0.37	0.95 (0.69 - 1.32)	0.76
CDKN2	rs10811661
TT	395/500	1.0 (ref)	0.93	1.0 (ref)	0.086
CT	142/202	0.88 (0.68 - 1.15)		0.85 (0.65 - 1.12)
CC	21/19	1.59 (0.83 - 3.03)		1.88 (0.93 - 3.81)
CC vs. TT/CT		1.65 (0.86 - 3.16)	0.13	1.97 (0.98 - 3.97)	0.057
CT/CC vs. TT		0.94 (0.73 - 1.21)	0.63	0.93 (0.71-1.21)	0.56
CDKAL1	rs7754840
GG	241/325	1.0 (ref)	0.35	1.0 (ref)	0.34
CG	254/313	1.15 (0.90 - 1.47)		1.21 (0.94 - 1.57)
CC	64/81	1.11 (0.76 - 1.61)		1.16 (0.78 - 1.73)
CC vs. GG/CG		1.04 (0.73 - 1.50)	0.87	1.05 (0.72 - 1.53)	0.80
CG/CC vs. GG		1.14 (0.91 - 1.44)	0.25	1.20 (0.94 - 1.53)	0.15
TCF2	rs4430796
AA	141/178	1.0 (ref)	0.39	1.0 (ref)	0.74
AG	297/374	0.94 (0.71 - 1.25)		0.95 (0.71 - 1.28)
GG	122/168	0.86 (0.62 - 1.20)		0.87 (0.61 - 1.24)
GG vs. AA/AG		0.90 (0.68 - 1.18)	0.43	0.90 (0.67 - 1.20)	0.48
AG/GG vs. AA		0.92 (0.70 - 1.20)	0.53	0.92 (0.70 - 1.23)	0.60

Table 2. Descriptive Characteristics of Kentucky Colon Cancer Study Population

Gene

SNP

Base Model*

Full Model†

Case/Control

p‡

*Logistic regression controlling for age, sex and race (558 cases and 698 controls). †Logistic regression controlling for age, sex, race, family history of colorectal cancer, non-steroidal anti-inflammatory. drug (NSAID) use and body mass index (BMI) (503 cases and 670 controls with complete data). ‡p-value of additive, dominant or recessive genetic model.

HHEX

rs1111875

217/241

1.0 (ref)

0.20

1.0 (ref)

0.22

255/348

0.80 (0.62 - 1.03)

0.79 (0.60 - 1.03)

88/131

0.85 (0.60 - 1.19)

0.87 (0.61- 1.24)

TT vs. CC/CT

0.97 (0.52 - 3.10)

0.84

1.00 (0.72 - 1.37)

0.98

CT/TT vs. CC

0.81 (0.64 - 1.03)

0.089

0.81 (0.63 - 1.04)

0.097

KCNJ11

rs5219

226/304

1.0 (ref)

0.93

1.0 (ref)

0.32

265/316

1.15 (0.90 - 1.47)

1.20 (0.92 - 1.56)

68/100

0.92 (0.63 - 1.32)

0.98 (0.67 - 1.56)

TT vs. CC/CT

0.85 (0.60 - 1.20)

0.35

0.89 (0.62 - 1.27)

0.89

CT/TT vs. CC

1.10 (0.87 - 1.39)

0.44

1.15 (0.90 - 1.47)

0.28

—

rs9300039

448/576

1.0 (ref)

0.64

1.0 (ref)

0.85

103/136

1.04 (0.78 - 1.41)

1.03 (0.75 - 1.41)

9/8

1.28 (0.48 - 3.45)

1.35 (0.46 - 3.95)

AA vs. CC/CA

1.28 (0.47 - 3.47)

0.63

1.35 (0.46 - 3.92)

0.59

AC/AA vs. CC

1.06 (0.79 - 1.41)

0.71

1.05 (0.77 - 1.42)

0.77

SLC30A8

rs13266634

274/329

1.0 (ref)

0.60

1.0 (ref)

0.61

230/319

0.92 (0.72 - 1.18)

0.88 (0.68 - 1.14)

55/71

0.94 (0.63 - 1.41)

0.99 (0.65 - 1.51)

TT vs. CC/CT

0.98 (0.67 - 1.44)

0.94

1.05 (0.70 - 1.57)

0.81

CT/TT vs. CC

0.93 (0.74 - 1.17)

0.52

0.90 (0.71 - 1.15)

0.40

FTO

rs9939609

217/261

1.0 (ref)

0.35

1.0 (ref)

0.40

252/336

0.90 (0.69 - 1.15)

0.84 (0.65 - 1.10)

90/121

0.86 (0.62 - 1.22)

0.84 (0.58 - 1.19)

AA vs. TT/AT vs. AA

0.88 (0.70 - 1.12)

0.54

0.92 (0.66 - 1.27)

0.61

AT/AA vs. TT

0.92 (0.67 - 1.25)

0.32

0.84 (0.65 - 1.08)

0.17

FTO

rs8050136

217/261

1.0 (ref)

0.42

1.0 (ref)

0.48

250/336

0.90 (0.70 - 1.16)

0.85 (0.65 - 1.11)

91/119

0.89 (0.64 - 1.25)

0.87 (0.61 - 1.11)

AA vs. CC/AC

0.90 (0.71 - 1.14)

0.72

0.86 (0.67 - 1.83)

0.23

AC/AA vs. CC

0.95 (0.70 - 1.29)

0.37

0.95 (0.69 - 1.32)

0.76

CDKN2

rs10811661

395/500

1.0 (ref)

0.93

1.0 (ref)

0.086

142/202

0.88 (0.68 - 1.15)

0.85 (0.65 - 1.12)

21/19

1.59 (0.83 - 3.03)

1.88 (0.93 - 3.81)

CC vs. TT/CT

1.65 (0.86 - 3.16)

0.13

1.97 (0.98 - 3.97)

0.057

CT/CC vs. TT

0.94 (0.73 - 1.21)

0.63

0.93 (0.71-1.21)

0.56

CDKAL1

rs7754840

241/325

1.0 (ref)

0.35

1.0 (ref)

0.34

254/313

1.15 (0.90 - 1.47)

1.21 (0.94 - 1.57)

64/81

1.11 (0.76 - 1.61)

1.16 (0.78 - 1.73)

CC vs. GG/CG

1.04 (0.73 - 1.50)

0.87

1.05 (0.72 - 1.53)

0.80

CG/CC vs. GG

1.14 (0.91 - 1.44)

0.25

1.20 (0.94 - 1.53)

0.15

TCF2

rs4430796

141/178

1.0 (ref)

0.39

1.0 (ref)

0.74

297/374

0.94 (0.71 - 1.25)

0.95 (0.71 - 1.28)

122/168

0.86 (0.62 - 1.20)

0.87 (0.61 - 1.24)

GG vs. AA/AG

0.90 (0.68 - 1.18)

0.43

0.90 (0.67 - 1.20)

0.48

AG/GG vs. AA

0.92 (0.70 - 1.20)

0.53

0.92 (0.70 - 1.23)

0.60