Associations between hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms and risk of developing breast cancer.
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.
Naidu
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R
School of Medicine and Health Sciences, Monash University Sunway Campus, Ehsan, Malaysia. kdrakeshna@hotmail.com
Har
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YC
Taib
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D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit