Tumor Biology
Title: Association of DCC, MLH1, GSTT1, GSTM1 and TP53 gene polymorphisms with
colorectal cancer in Kazakhstan
Running Title: Colorectal Cancer Polymorphisms in Kazakhstan
Leyla Djansugurova1, Gulnur Zhunussova1, 3, Elmira Khussainova1, Olzhas Iksan1, Georgiy Afonin2, Dilyara
Kaidarova2 and M. Iqbal Parker3
1
Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Almaty 050060, Kazakhstan
2
Almaty Oncology Centre, Almaty 050060, Kazakhstan
3
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, and
Medical Biochemistry/IDM, UCT, Observatory, Cape Town, South Africa
Corresponding Author:
Professor Leyla Djansugurova
Laboratory of Molecular Genetics
Institute of General Genetics and Cytology
Republic of Kazakhstan, Almaty, 050060
Al-Farabi ave., 93
Tel: +77272695014
Fax: +77272694587
E-mail: leylad@mail.ru
SUPPLEMENTARY TABLES
Table S1 Association of tobacco smoking with DCC 32008376 polymorphism
Type of
Genotype CRC patients
polymorphism
(%)
Smokers and ex-smokers
DCC - 32008376
G/G
31 (51.67)
G/A
26 (43.33)
A/A
3 (5.00)
DCC – 32008376
G/G
31 (51.67)
Dominant model G/A + A/A 29 (48.33)
DCC - 32008376 G/G + G/A 57 (95.00)
Recessive model
A/A
3 (5.00)
Non-smokers
DCC - 32008376
G/G
89 (47.09)
G/A
91 (48.15)
A/A
9 (4.76)
DCC – 32008376
G/G
89 (47.09)
Dominant model G/A + A/A 100 (52.91)
DCC - 32008376 G/G + G/A 180 (95.24)
Recessive model
A/A
9 (4.76)
χ2
Controls (%) OR
95%CI
36 (52.94)
22 (32.35)
10 (14.71)
36 (52.94)
32 (47.06)
58 (85.29)
10 (14.71)
0.95
1.60
0.31
0.95
1.05
3.28
0.31
0.47 – 1.90
0.78 – 3.29 3.99 0.14
0.08 – 1.17
0.47 – 1.90
0.02 0.89
0.53 – 2.11
0.86 – 12.52
3.29 0.07
0.08 – 1.17
68 (39.08)
80 (45.98)
26 (14.94)
68 (39.08)
106 (60.92)
148 (85.06)
26 (14.94)
1.39
1.09
0.28
1.39
0.72
3.51
0.28
0.91 – 2.11
0.72 – 1.65
0.13 – 0.63
0.91 – 2.11
0.47 – 1.09
1.60 – 7.73
0.13 – 0.63
1
P
11.17 0.004
2.37 0.12
10.78 0.001
Table S2 Association of codon 72 TP53 polymorphism with CRC - dominant and recessive
models
Type of
Genotype CRC patients Controls (%) OR
95%CI
χ2
P
polymorphism
(%)
TP53 - 72
Pro/Pro 99 (39.92) 36 (14.88)
3.80
2.46 – 5.88
Dominant
Pro/Arg + 113+36=149 104+102=206 0.26
0.17 – 0.41
38.48
<0.0001
model
Arg/Arg (60.08)
(85.13)
TP53 - 72
Pro/Pro + 99+113=212 36+104=140 4.29
2.77 – 6.63
Recessive
Pro/Arg (85.48)
(57.86)
46.23
0
model
Arg/Arg 36 (14.52) 102 (42.15)
0.23
0.15 – 0.36
Table S3 Association of tobacco smoking with codon 72 TP53 polymorphism
Type of
Genotype
polymorphism
Smokers and ex-smokers
TP53 -72
Pro/Pro
Pro/Arg
Arg/Arg
TP53 - 72
Pro/Pro
Dominant model Pro/Arg +
Arg/Arg
TP53 - 72
Pro/Pro +
Recessive model Pro/Arg
Arg/Arg
Non-smokers
TP53 -72
Pro/Pro
Pro/Arg
Arg/Arg
TP53 - 72
Pro/Pro
Dominant model Pro/Arg +
Arg/Arg
TP53 - 72
Pro/Pro +
Recessive model Pro/Arg
Arg/Arg
χ2
CRC patients Controls (%) OR
(%)
95%CI
P
23 (38.33)
29 (48.33)
8 (13.33)
23 (38.33)
37 (61.66)
7 (10.14)
29 (42.03)
33 (47.83)
7 (10.14)
62 (89.86)
5.51
1.29
0.17
5.51
0.18
2.15 – 14.08 23.26 <0.0001
0.64 – 2.59
0.07 – 0.41
2.15 – 14.08 14.29 0.0002
0.07 – 0.46
52 (86.66)
36 (52.17)
5.96 2.47 – 14.39 17.61 <0.0001
8 (13.33)
33 (47.83)
0.17 0.07 – 0.41
76 (40.43)
84 (44.68)
28 (14.89)
76 (40.43)
112 (59.57)
29 (16.76)
75 (43.35)
69 (39.88)
29 (16.76)
144 (83.23)
3.37
1.06
0.26
3.37
0.30
160 (85.11)
104 (60.11)
3.79 2.29 – 6.27 28.63 <0.0001
28 (14.89)
69 (39.88)
0.26 0.16 – 0.44
2.06 – 5.52 38.32 <0.0001
0.70 – 1.60
0.16 – 0.44
2.06 – 5.52 24.46 <0.0001
0.18 – 0.49
Table S4 Association of GSTM1 deletion polymorphism with CRC - dominant and recessive
models
Type of
Genotype
CRC patients Controls
OR 95%CI
χ2
P
polymorphism
(%)
(%)
GSTM1
+/+
90 (36.14)
118 (48.16) 0.61 0.43 – 0.87 7.32 0.007
Dominant model +/- and -/34+125=159 40+87=127 1.64 1.15 – 2.35
(63.85)
(51.84)
GSTM1
+/+ and +/- 90+34=124 118+40=158 0.55 0.38 – 0.78 10.88 0.001
Recessive model
(49.79)
(64.49)
-/125 (50.20) 87 (35.51)
1.83 1.28 – 2.63
2