TY - JOUR
T1 - Genetic susceptibility of epidermal growth factor +61A>G and transforming growth factor β1 -509C>T gene polymorphisms with gallbladder cancer
AU - Vishnoi, Monika
AU - Pandey, Sachchida Nand
AU - Modi, Dinesh Raj
AU - Kumar, Ashok
AU - Mittal, Balraj
N1 - Funding Information:
The study was supported by research grants from the Department of Science and Technology and the Indian Council of Medical Research, Government of India.
PY - 2008/6
Y1 - 2008/6
N2 - Epidermal growth factor (EGF) and transforming growth factor β1 (TGFβ1) play important roles in tumor biology. Single nucleotide polymorphisms in EGF and TGFB1 genes alter the expression of these growth factors and influence the tumorigenesis process. The aim of our present study was to determine the association of EGF+61A>G (rs4444903) and TGFB1-509C>T (rs1800469) gene polymorphism with susceptibility to gallbladder cancer (GBC). The present case-control association study was carried out in 126 confirmed GBC patients and 190 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. The GG genotype of EGF+61A>G was significantly associated with GBC [p = 0.012, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.19-4.15] in comparison to healthy subjects. Analysis based on gender indicated risk due to GG genotype was limited to female GBC patients (p = 0.003, OR = 3.45, 95% CI = 1.52-7.82). Upon stratification of GBC patients on the basis of the presence or absence of gallstones, the risk due to EGF polymorphism was not modulated by the status of gallstones. The TGFB1-509C>T polymorphism was not associated with GBC. Also, we did not find any association of this polymorphism when GBC patients were subdivided on the basis of gender. However, after stratification of GBC patients on the status of gallstones, we determined that the CT genotype of TGFB1 was associated with increased risk of GBC without gallstones (p value = 0.030, OR = 2.90, 95% CI = 1.26-6.69). Furthermore, the combination of the GG genotype of EGF and the CT genotype of TGFB1 demonstrated synergistic increase in risk of GBC.In conclusion, the higher producing +61G allele of EGF and -509 CT genotype of TGFB1 synergistically increase the susceptibility of gallbladder cancer (p value = 0.003). Further study in large samples size is required to confirm our findings.
AB - Epidermal growth factor (EGF) and transforming growth factor β1 (TGFβ1) play important roles in tumor biology. Single nucleotide polymorphisms in EGF and TGFB1 genes alter the expression of these growth factors and influence the tumorigenesis process. The aim of our present study was to determine the association of EGF+61A>G (rs4444903) and TGFB1-509C>T (rs1800469) gene polymorphism with susceptibility to gallbladder cancer (GBC). The present case-control association study was carried out in 126 confirmed GBC patients and 190 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. The GG genotype of EGF+61A>G was significantly associated with GBC [p = 0.012, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.19-4.15] in comparison to healthy subjects. Analysis based on gender indicated risk due to GG genotype was limited to female GBC patients (p = 0.003, OR = 3.45, 95% CI = 1.52-7.82). Upon stratification of GBC patients on the basis of the presence or absence of gallstones, the risk due to EGF polymorphism was not modulated by the status of gallstones. The TGFB1-509C>T polymorphism was not associated with GBC. Also, we did not find any association of this polymorphism when GBC patients were subdivided on the basis of gender. However, after stratification of GBC patients on the status of gallstones, we determined that the CT genotype of TGFB1 was associated with increased risk of GBC without gallstones (p value = 0.030, OR = 2.90, 95% CI = 1.26-6.69). Furthermore, the combination of the GG genotype of EGF and the CT genotype of TGFB1 demonstrated synergistic increase in risk of GBC.In conclusion, the higher producing +61G allele of EGF and -509 CT genotype of TGFB1 synergistically increase the susceptibility of gallbladder cancer (p value = 0.003). Further study in large samples size is required to confirm our findings.
KW - Epidermal growth factor
KW - Gallbladder cancer
KW - Genetic susceptibility
KW - Polymorphism
KW - Transforming growth factor
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U2 - 10.1016/j.humimm.2008.04.004
DO - 10.1016/j.humimm.2008.04.004
M3 - Article
C2 - 18571008
AN - SCOPUS:50949125238
SN - 0198-8859
VL - 69
SP - 360
EP - 367
JO - Human Immunology
JF - Human Immunology
IS - 6
ER -