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 8, Number 5, October 2017, pages 162-170


CTLA-4 Genetic Variants (rs11571317 and rs3087243): Role in Susceptibility and Progression of Breast Cancer

Figures

Figure 1.
Figure 1. Gel images of selected polymorphisms in the present study.
Figure 2.
Figure 2. The in-silico analysis showed CTLA-4 gene rs11571317 SNP and possible associated transcription factors.
Figure 3.
Figure 3. Comparative allele frequency of CTLA-4 SNP rs11571317 in various study populations. Source: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=11571317
Figure 4.
Figure 4. Comparative allele frequency of CTLA-4 SNP rs3087243 in various study populations. Source: https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=3087243

Tables

Table 1. Clinical Characteristics of BC Patients
 
Clinical parametersValues
Tumor stage
  T1-2160 (56)
  T3-4125 (44)
Lymph node status
  LN-ve48 (17)
  LN+ve237 (83)
Metastatic
  M0237 (82)
  M148 (18)
Duration of disease
  < 6 months150 (52)
  7 - 12 months83 (29)
  > 12 months52 (19)
DOD
  < 6 months
    T1-2100 (66)
    T3-450 (44)
    LN-ve34 (22)
    LN+ve116 (78)
    M0130 (87)
    M120 (13)

 

Table 2. Demographical and Clinical Information of Breast Cancer Patients and Healthy Controls
 
CategoryControls (N, %)Breast cancer patients (N, %)t-, z-test (P value)
*t-test: mean age, age at onset of breast cancer (years), and body mass index (kg/m2). z-test: age at marriage(years), age at first pregnancy, parity, consanguinity, familial incidence, diet, lactation, area of living, and occupation.
Mean age*285
48.45 ± 13.49
285
51.29 ± 10.75
0.005
Range (years)18 - 9025 - 86
Age at onset of breast cancer (years)*48.5 ± 11
  ≤ 48-142 (50)
40.50 ± 5.68
-
  > 48-143 (50)
57.64 ± 7.09
-
Age at marriage (years)
  ≤ 18179 (62)185 (64)0.69
  19 - 30105 (37)93 (33)0.55
  > 301 (0.3)7 (3)-
  Unmarried0 (0)0 (0)-
Age at first pregnancy
  ≤ 18138 (48)107 (37)0.08
  19 - 30144 (50)157 (54)0.48
  > 303 (2)9 (3)0.92
  00 (0)12 (4)-
Parity
  Parous285 (100)273 (95)< 0.01
  Nulliparous0 (0)12 (5)-
Consanguinity
  Yes0 (0)29 (10)-
  No285 (100)256 (98)< 0.01
Familial incidence
  No206 (72)-
  BC15 (5)-
  Other cancer29 (10)-
  Life style-related diseases35 (12)-
Variables
  Diet
    Vegetarians35 (12)40 (14)0.79
    Non-vegetarians250 (88)245 (86)0.50
  Body mass index (kg/m2)*24.5 ± 3.824.9 ± 50.23
    < 25176 (61)
22.2 ± 1.9
140 (49)
21.3 ± 2
< 0.01
    ≥ 25108 (39)
28.27 ± 3.1
145 (51)
27.8 ± 3.2
0.19
  Breast feeding
    Yes200 (100)279 (98)< 0.01
    No0 (0)6 (2)-
  Area of living
    Rural95 (33)66 (23)0.16
    Urban190 (66)219 (77)< 0.01
  Occupation
    Housewives107 (37)165 (58)< 0.01
    Agriculture workers177 (62)120 (42)< 0.01

 

Table 3. Genotype and Allele Frequencies of CTLA-4 (rs11571317) Gene Polymorphism in South Indian Breast Cancer Patients, Healthy Controls and Multiple Logistic Regression Analysis for BC Clinical Pathological Features
 
rs11571317CC, N (%)CT, N (%)TT, N (%)χ2 value (P-value)Minor allele frequency TGroup comparisonOR (95% CI)P-value
Controls (285)
Patients (285)
39 (13.5)
89 (31.1)
246 (86.5)
196 (68.9)
0 (0)
0 (0)
24.19 (< 0.01)0.43
0.34
CC vs. others
CT vs. others
TT vs. others
2.86 (1.80 - 4.36)
0.34 (0.22 - 0.53)
-
< 0.01
< 0.01
-
HWE: controls: χ2 = 164.2 (P < 0.05); patients: χ2 = 78.2 (P < 0.05)
VariablesCC vs. CT: OR (CI)P-valueCT vs. CC: OR (CI)P-value
AAO1.05 (0.58 - 1.91)0.851.06 (0.58 - 1.92)0.83
Tumor status0.98 (0.50 - 1.91)0.960.98 (0.50 - 1.92)0.97
LN status1.86 (0.59 - 5.80)0.281.26 (0.57 - 2.79)0.55
Metastasis2.64 (0.92 - 7.60)0.072.64 (0.92 - 7.58)0.07
DOD < 6 months vs. > 6 months1.12 (0.61 - 2.07)0.691.15 (0.62 - 2.11)0.64

 

Table 4. Genotype and Allele Frequencies of CTLA-4 rs3087243 Gene Polymorphism in South Indian Breast Cancer Patients, Healthy Controls and Multiple Logistic Regression Analysis for BC Clinical Pathological Features
 
rs3087243GG, N (%)GA, N (%)AA, N (%)χ2 value (P-value)Minor allele frequency AGroup comparisonOR (95% CI)P-value
Controls
Patients
74 (26)
71 (25)
202 (71)
197 (70)
9 (3)
17 (5)
1.95 (= 0.376)0.39
0.41
GG vs. others
GA vs. others
AA vs. others
0.94 (0.64 - 1.37)
0.91 (0.64 - 1.31)
1.94 (0.85 - 4.4)
0.84
0.71
0.15
HWE: controls: χ2 = 69.9 (P < 0.05); patients: χ2 = 53.6 (P < 0.05)
VariablesGG vs. GA + AA: OR (CI)P-valueGA vs. GG + AA: OR (CI)P-valueAA vs. GG + GA: OR (CI)P-value
AAO1.44 (0.70 - 2.94)0.310.57 (0.30 - 1.08)0.081.86 (0.67 - 5.16)0.23
Tumor status0.01 (0.0043 - 0.09)< 0.01*6.28 (3.01 - 13.07)< 0.01*3.46 (1.02 - 11.67)0.04*
LN status1.38 (0.61 - 3.11)0.430.68 (0.31 - 1.52)0.350.91 (0.17 - 4.90)0.91
Metastasis0.97 (0.17 - 5.53)0.973.60 (0.94 - 13.78)0.06-0.99
DOD < 6 months vs. > 6 months(0.91 - 4.02)0.080.62 (0.32 - 1.19)0.150.84 (0.29 - 2.46)0.76

 

Table 5. The Reference Motif cgtgggtt (78.23) Threshold Value Is Changed to Mutant catgggtt (51.7)
 
Splice site typeMotifNew splice siteWild typeMutantIf cryptic site uses exon length variationVariation (%)
DONORAacgtgggtAACatgggt78.5351.7NASITE BROKEN -34.17

 

Table 6. Haplotype Analysis of CTLA-4 (rs11571317 and rs3087243) Gene Polymorphisms in Breast Cancer Patients and Controls and Haplotypes Association With Epidemiologic, Clinical Parameters in South Indian Breast Cancer Patients
 
HaplotypeFrequencyOdds ratio (95% CI)P-value
C-A0.39561.00-
T-G0.38770.40 (0.25 - 0.62)< 0.01
C-G0.21671.31 (0.91 - 1.89)0.15
Global haplotype association P-value < 0.0001
S. no.HaplotypeAAO < 48 years vs. > 49 years patientsTumor sizeLN statusMetastasisDOD < 6 months vs. > 6 months
C1C-G1.001.001.001.001.00
C2C-A2.00 (0.75 - 5.28)
P > 0.05
3.61 (1.10 - 11.86)
P < 0.05
2.61 (0.84 - 8.15)
P > 0.05
0.35 (0.10 - 1.22)
P > 0.05
0.24 (0.07 - 0.77)
P < 0.05
C3T-G1.68 (0.68 - 4.14)
P > 0.05
0.24 (0.03 - 1.67)
P > 0.05
1.95 (0.60 - 6.34)
P > 0.05
0.60 (0.13 - 2.87)
P > 0.05
0.59 (0.19 - 1.79)
P > 0.05
C4T-A0.65 (0.17 - 2.50)
P > 0.05
15.81 (4.96 - 50.40)
P < 0.05
2.13 (0.74 - 6.09)
P > 0.05
3.98 (1.25 - 12.63)
P < 0.05
0.67 (0.18 - 2.53)
P > 0.05