BACKGROUND: Hypoxia inducible factor 1 alpha (HIF-1A) is activated by low oxygen condition tension, a key regulator of the gene involved in the cellular response to hypoxia. Tumors exhibiting extensive hypoxia are more aggressive than tumors oxygenized better. METHODS: To evaluate the potential role of the polymorphisms of HIF-1A in the etiology of breast cancer, histologically confirmed incident breast cancer cases (n=1599) and control subjects (n=1536) were recruited. RESULTS: Two selected SNPs (Ex15+197C>T and P582S) were not associated with overall breast cancer risk (TT vs. CC: OR=0.9, 95% CI=0.6-1.5, Ser/Ser vs. Pro/Pro: OR=5.5, 95% CI=0.7-45.4, respectively). However, when stratified analyses were performed, significant associations were observed between Ser/Ser genotype at codon 582 and breast cancer risk among women with larger tumor size (>2 cm) (OR=10.1, 95% CI=1.1-91.1) or without lymph node involvement (OR=9.3, 95% CI=1.1-79.4), although confidence intervals were wide. CONCLUSIONS: Our findings support the hypothesis that the HIF-1Alpha P582S variant may confer susceptibility to subgroups of breast cancer in Korean women. However, further study is warranted due to low statistical power caused by very low minor allele frequencies.
BACKGROUND:Hypoxia inducible factor 1 alpha (HIF-1A) is activated by low oxygen condition tension, a key regulator of the gene involved in the cellular response to hypoxia. Tumors exhibiting extensive hypoxia are more aggressive than tumors oxygenized better. METHODS: To evaluate the potential role of the polymorphisms of HIF-1A in the etiology of breast cancer, histologically confirmed incident breast cancer cases (n=1599) and control subjects (n=1536) were recruited. RESULTS: Two selected SNPs (Ex15+197C>T and P582S) were not associated with overall breast cancer risk (TT vs. CC: OR=0.9, 95% CI=0.6-1.5, Ser/Ser vs. Pro/Pro: OR=5.5, 95% CI=0.7-45.4, respectively). However, when stratified analyses were performed, significant associations were observed between Ser/Ser genotype at codon 582 and breast cancer risk among women with larger tumor size (>2 cm) (OR=10.1, 95% CI=1.1-91.1) or without lymph node involvement (OR=9.3, 95% CI=1.1-79.4), although confidence intervals were wide. CONCLUSIONS: Our findings support the hypothesis that the HIF-1AlphaP582S variant may confer susceptibility to subgroups of breast cancer in Korean women. However, further study is warranted due to low statistical power caused by very low minor allele frequencies.
Authors: Alexey Y Kolyada; Hocine Tighiouart; Mary C Perianayagam; Orfeas Liangos; Nicolaos E Madias; Bertrand L Jaber Journal: Kidney Int Date: 2009-03-11 Impact factor: 10.612