title: Single nucleotide polymorphisms in the HIF-1α gene and chemoradiotherapy of locally advanced rectal cancer.
abstract: The aim of this study was to investigate the predictive impact of polymorphisms in the HIF-1α gene on the response to chemoradiotherapy (CRT) in rectal cancer. This study included two cohorts of patients with locally advanced rectal cancer receiving long-course CRT. The HIF-1α C1772T (rs11549465), G1790A (rs11549467) and c(*)191T>C (rs2057482) polymorphisms were investigated in the test cohort (n=65), and HIF-1α c(*)191T>C was analysed in the validation cohort (n=198). No correlations were identified between the polymorphisms and clinicopathological factors. The HIF-1α C1772T and HIF-1α G1790A polymorphisms demonstrated no correlation with tumour response to CRT in the test cohort. The HIF-1α c(*)191T>C CC genotype was marginally associated with a higher rate of complete tumour response (P=0.05) in the test cohort, while the HIF-1α c(*)191T>C CC genotype was associated with a poor tumour response (P=0.03) in the validation cohort. In conclusion, these results suggest that HIF-1α polymorphisms have no value as predictors of response to neoadjuvant CRT in rectal cancer. The results of the HIF-1α c(*)191T>C in two cohorts differ and emphasise the importance of biomarker validation.
authors.affiliation: Department of Oncology, Vejle Hospital, Vejle 7100; ; Faculty of Health Sciences, Institute of Regional Health Services Research, University of Southern  Denmark , Odense 5000;
authors.forename: Birgitte Mayland
authors.initials: BM
authors.lastname: Havelund
authors.forename: Karen-Lise Garm
authors.initials: KL
authors.lastname: Spindler
authors.forename: John
authors.initials: J
authors.lastname: Ploen
authors.forename: Rikke Fredslund
authors.initials: RF
authors.lastname: Andersen
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen