Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival.
Identifying genes associated with familial inheritance of breast cancer continues to be a major goal of current research as the known high penetrance genes could be attributable for only a small percentage of the risk. So, it is hypothesized that the low penetrance genes may also modify the risk for familial breast cancer. In the present case-control study, undertaken to examine the influence of polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597 women including 222 sporadic breast cancer patients, 125 familial breast cancer patients and 250 females with no history of cancer as controls were genotyped by PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Interestingly, GSTM1 deletion was found to be significantly associated only with familial breast cancer (OR = 2.0; 95%CI = 1.252-3.128) while GSTT1 was associated only with sporadic breast cancer (OR = 2.3; 95%CI = 1.336-3.970). GSTP1 Ile105Val polymorphism was associated neither with sporadic nor familial breast cancer susceptibility (P value > 0.05). The GST genotypes did not have any effect on the survival of both familial and sporadic breast cancer patients. However, familial breast cancer patients with GSTM1 null genotype had a relative risk of 0.42 (95%CI = 0.18-0.97) for an advanced disease stage. The results indicate that, in addition to the known high penetrance genes, certain low penetrance genes may also play a role, in the familial inheritance of breast cancer. It is also noticed that all the polymorphisms associated with sporadic breast cancer are not associated with familial breast cancer.
Syamala
Volga S
VS
Division of Cancer Research, Regional Cancer Centre, Trivandrum , 695011, Kerala, India.
Sreeja
Leelakumari
L
Syamala
Vani
V
Raveendran
Praveenkumar B
PB
Balakrishnan
Rajan
R
Kuttan
Ratheesan
R
Ankathil
Ravindran
R
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D016001:Confidence Intervals; D004198:Disease Susceptibility; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human