Detection and relevance of germline genetic polymorphisms in glutathione S-transferases (GSTs) in breast cancer patients from northern Indian population.
BACKGROUND
Glutathione S-transferases (GSTs) are polymorphic superfamily of detoxification enzymes that detoxify therapeutic drugs and various carcinogens. We undertook a case-control study in northern Indian population based sample consisting of 413 patients and 410 controls to evaluate association of null genotype in GSTM1 and GSTT1 along with polymorphism in GSTP1 (A-->G) with breast cancer risk.


METHODS
Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) were calculated by unconditional logistic regression analysis adjusting for various confounding factors.


RESULTS
In this case-control study, we observed a positive correlation between family history of breast cancer and risk of breast cancer (OR = 2.06; 95% CI = 1.47-2.92). We found a significantly increased breast cancer risk associated with GSTM1 null genotype (OR = 2.28; 95% CI = 1.65-2.97) and homozygote mutants in GSTP1 (OR = 2.59; 95% CI = 1.67-4.39). However, we found no association between GSTT1 null genotype with overall breast cancer risk (OR = 1.04; 95% CI = 0.76-1.59). The three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in fourfold increase in breast cancer risk (OR = 4.02; 95% CI = 1.99-8.51).


CONCLUSIONS
The findings of this study are in line with previously published reports that show an overall association with GSTM1 and GSTP1 polymorphisms with breast cancer risk. Our results suggest that the variants in low penetrance genes such as GSTM1, GSTT1 and GSTP1 are associated with an increased breast cancer risk thereby suggesting their contribution in the etiology of breast cancer.
Saxena
Anubha
A
Human Genetics Laboratory, Department of Biosciences, Jamia Millia Islamia, A Central University, New Delhi, 110025, India.
Dhillon
Varinderpal S
VS
Raish
Mohammad
M
Asim
Mohammad
M
Rehman
Shabeena
S
Shukla
N K
NK
Deo
S V S
SV
Ara
Anjum
A
Husain
Syed Akhtar
SA
D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
D004273:DNA, Neoplasm; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human