Rare variant of hypoxia-inducible factor-1alpha (HIF-1A) and breast cancer risk in Korean women.
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.
Lee
Ji-Young
JY
Department of Preventive Medicine, Seoul National University College of Medicine, Jongnoo-Gu, Seoul, South Korea.
Choi
Ji-Yeob
JY
Lee
Kyoung-Mu
KM
Park
Sue Kyung
SK
Han
So-Hee
SH
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Kim
Dong-Hyun
DH
Hong
Yun-Chul
YC
Ha
Eunhee
E
Yoo
Keun-Young
KY
Ambrosone
Christine B
CB
Kang
Daehee
D
D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007723:Korea; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit