World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 6, Number 4, August 2015, pages 394-397

Effect of MTHFR Polymorphisms on Gastrointestinal Cancer Risk in Italy

**Table 1.** Cancer Subtypes in the Patient’s Cohort
Cancer type	No. (%)
Colorectal cancer	553 (100)
Colon cancer	290 (52)
Rectal cancer	263 (48)
Esophageal/gastric cancer	138 (100)
Gastric cancer	123 (89)
Esophageal cancer	11 (8)
Junction E/G	4 (3)
Bilio-pancreatic cancer	99 (100)
Pancreatic cancer	74 (74.7)
Biliary duct cancer	25 (25.3)

Table 1. Cancer Subtypes in the Patient’s Cohort

Cancer type

No. (%)

Colorectal cancer

553 (100)

Colon cancer

290 (52)

Rectal cancer

263 (48)

Esophageal/gastric cancer

138 (100)

Gastric cancer

123 (89)

Esophageal cancer

11 (8)

Junction E/G

4 (3)

Bilio-pancreatic cancer

99 (100)

Pancreatic cancer

74 (74.7)

Biliary duct cancer

25 (25.3)

**Table 2.** Genotype and Allele Frequencies in the Analyzed Population (n = 991)
MTHFR polymorphism group	Genotype, n (%)	P*	Alleles, n (%)	P*
*Difference in genotypes or alleles distribution between each cancer group and the control group assessed by X² statistical testing.
	CC	CT	TT		C	T
C677T
Control (n = 202)	76 (37.6)	98 (48.5)	28 (13.9)		250 (62.9)	154 (38.1)
Colorectal cancer (n = 550)	163 (24.7)	268 (48.7)	119 (21.6)	0.023	594 (54.0)	506 (46.0)	0.06
Esophageal/gastric cancer (n = 138)	37 (26.8)	69 (50.0)	32 (23.2)	0.031	143 (51.8)	133 (48.2)	0.009
Pancreatic/biliar cancer (n = 97)	32 (33.0)	51 (52.6)	14 (14.4)	0.733	115 (59.3)	79 (40.7)	0.541
	AA	AT	TT		A	T
A1298T
Control (n = 202)	103 (51.0)	80 (39.6)	19 (9.4)		286 (70.8)	118 (29.2)
Colorectal cancer (n = 553)	263 (47.5)	232 (41.9)	58 (10.6)	0.695	758 (68.5)	348 (31.5)	0.401
Esophageal/gastric cancer (n = 138)	60 (43.8)	66 (48.2)	11 (8.0)	0.298	186 (67.9)	88 (32.1)	0.419
Pancreatic/biliar cancer (n = 99)	49 (49.5)	45 (45.5)	5 (5.0)	0.340	143 (72.2)	55 (27.8)	0.716

Table 2. Genotype and Allele Frequencies in the Analyzed Population (n = 991)

MTHFR polymorphism group

Genotype, n (%)

Alleles, n (%)

*Difference in genotypes or alleles distribution between each cancer group and the control group assessed by X² statistical testing.

C677T

Control (n = 202)

76 (37.6)

98 (48.5)

28 (13.9)

250 (62.9)

154 (38.1)

Colorectal cancer (n = 550)

163 (24.7)

268 (48.7)

119 (21.6)

0.023

594 (54.0)

506 (46.0)

0.06

Esophageal/gastric cancer (n = 138)

37 (26.8)

69 (50.0)

32 (23.2)

0.031

143 (51.8)

133 (48.2)

0.009

Pancreatic/biliar cancer (n = 97)

32 (33.0)

51 (52.6)

14 (14.4)

0.733

115 (59.3)

79 (40.7)

0.541

A1298T

Control (n = 202)

103 (51.0)

80 (39.6)

19 (9.4)

286 (70.8)

118 (29.2)

Colorectal cancer (n = 553)

263 (47.5)

232 (41.9)

58 (10.6)

0.695

758 (68.5)

348 (31.5)

0.401

Esophageal/gastric cancer (n = 138)

60 (43.8)

66 (48.2)

11 (8.0)

0.298

186 (67.9)

88 (32.1)

0.419

Pancreatic/biliar cancer (n = 99)

49 (49.5)

45 (45.5)

5 (5.0)

0.340

143 (72.2)

55 (27.8)

0.716

**Table 3.** Single SNPs Association Analysis of MTHFR Polymorphism With Risk of Each Type of Cancer, According to Multiple Inheritance Models
MTHFR polymorphism	Model	Genotype	Colorectal cancer	Esophageal/gastric cancer	Pancreatic/biliar cancer
*By logistic regression model adjusted for age and sex.
C677T	Co-dominant	CC	1.00	0.02	1.00	0.031	1.00	0.73
CT	1.28 (0.89 - 1.82)	1.45 (0.88 - 2.38)	1.24 (0.72 - 2.11)
TT	1.98 (1.21 - 3.25)	2.35 (1.24 - 4.46)	1.19 (0.55 - 2.55)
Dominant	CC	1.00	0.039	1.00	0.036	1.00	0.43
CT + TT	1.43 (1.02 - 2.01)	1.65 (1.03 - 2.64)	1.23 (0.74 - 2.04)
Recessive	CC + CT	1.00	0.014	1.00	0.028	1.00	0.89
TT	1.72 (1.10 - 2.68)	1.88 (1.07 - 3.29)	1.05 (0.52 - 2.10)
Log-additive	-	1.38 (1.09 - 1.74)	0.0064	1.52 (1.11 - 2.09)	0.0087	1.12 (0.78 - 1.61)	0.53
A1298C	Co-dominant	AA	1.00	0.7	1.00	0.29	1.00	0.32
AT	1.14 (0.81 - 1.60)	1.42 (0.90 - 2.23)	1.18 (0.72 - 1.95)
TT	1.20 (0.68 - 2.11)	0.99 (0.44 - 2.23)	0.55 (0.20 - 1.57)
Dominant	AA	1.00	0.4	1.00	0.19	1.00	0.81
AT + TT	1.15 (0.83 - 1.58)	1.34 (0.86 - 2.06)	1.06 (0.66 - 1.72)
Recessive	AA + AT	1.00	0.66	1.00	0.66	1.00	0.17
TT	1.13 (0.65 - 1.95)	1.42 (0.91 - 2.20)	0.51 (0.19 - 1.42)
Log-additive	-	1.11 (0.87 - 1.42)	0.41	1.15 (0.82 - 1.61)	0.42	0.93 (0.64 - 1.36)	0.71

Table 3. Single SNPs Association Analysis of MTHFR Polymorphism With Risk of Each Type of Cancer, According to Multiple Inheritance Models

MTHFR polymorphism

Model

Genotype

Colorectal cancer

Esophageal/gastric cancer

Pancreatic/biliar cancer

OR (95% CI)

*By logistic regression model adjusted for age and sex.

C677T

Co-dominant

1.00

0.02

1.00

0.031

1.00

0.73

1.28 (0.89 - 1.82)

1.45 (0.88 - 2.38)

1.24 (0.72 - 2.11)

1.98 (1.21 - 3.25)

2.35 (1.24 - 4.46)

1.19 (0.55 - 2.55)

Dominant

1.00

0.039

1.00

0.036

1.00

0.43

CT + TT

1.43 (1.02 - 2.01)

1.65 (1.03 - 2.64)

1.23 (0.74 - 2.04)

Recessive

CC + CT

1.00

0.014

1.00

0.028

1.00

0.89

1.72 (1.10 - 2.68)

1.88 (1.07 - 3.29)

1.05 (0.52 - 2.10)

Log-additive

1.38 (1.09 - 1.74)

0.0064

1.52 (1.11 - 2.09)

0.0087

1.12 (0.78 - 1.61)

0.53

A1298C

Co-dominant

1.00

0.7

1.00

0.29

1.00

0.32

1.14 (0.81 - 1.60)

1.42 (0.90 - 2.23)

1.18 (0.72 - 1.95)

1.20 (0.68 - 2.11)

0.99 (0.44 - 2.23)

0.55 (0.20 - 1.57)

Dominant

1.00

0.4

1.00

0.19

1.00

0.81

AT + TT

1.15 (0.83 - 1.58)

1.34 (0.86 - 2.06)

1.06 (0.66 - 1.72)

Recessive

AA + AT

1.00

0.66

1.00

0.66

1.00

0.17

1.13 (0.65 - 1.95)

1.42 (0.91 - 2.20)

0.51 (0.19 - 1.42)

Log-additive

1.11 (0.87 - 1.42)

0.41

1.15 (0.82 - 1.61)

0.42

0.93 (0.64 - 1.36)

0.71