The C1772T, G1790A and C111A polymorphisms of Hypoxia-inducible factor-1alpha (HIF-1alpha) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 breast cancer patients and 275 normal and healthy women. We investigated the association between HIF-1alpha polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the breast cancer cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of breast cancer. Significant relationship was observed also between T allele and breast cancer risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing breast cancer, and presence of 1772T allele may be a useful genetic marker for tumor prognosis.
The HER2 codon Ile655Val and Cyclin D1 (CCND1) G870A polymorphisms were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Peripheral blood samples were collected from 230 breast cancer patients, and 200 normal and healthy women who had no history of breast disease or breast cancer. We evaluated the association between HER2 or CCND1 polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of HER2 (P=0.163 vs P=0.0622) and CCND1 (P=0.377 vs P=0.284) polymorphisms were not significantly different between the breast cancer cases and normal subjects, respectively. Women who were Ile/Val heterozygotes (OR=1.48; 95% CI, 0.91-2.43), Val/Val homozygotes (OR=1.93; 95% CI, 0.51-7.77) and carriers of Val allele genotype (OR=1.53; 95% CI, 0.95-2.45) were not significantly associated with increased breast cancer risk. Similarly, women who were homozygous (OR=1.34; 95% CI, 0.77-2.34) or heterozygous (OR=0.98; 95% CI, 0.60-1.60) for A allele, or carriers of A allele genotype (OR=1.10; 95% CI, 0.70-1.73) were not associated with breast cancer risk. Analysis on clinico-pathological parameters showed that Val allele genotype was significantly correlated with nodal metastases but A allele genotype was not associated with any of the variables. Our findings suggest that the polymorphic alleles of HER2 and CCND1 may not play an important role as genetic markers for breast cancer risk, but presence of Val allele may be useful for tumor prognosis.