Single nucleotide polymorphisms in the HIF‑1α gene and chemoradiotherapy of locally advanced rectal cancer

Havelund,Birgitte  Mayland; Spindler,Karen‑Lise  Garm; Ploen,John; Andersen,Rikke  Fredslund; Jakobsen,Anders

doi:10.3892/ol.2012.837

Single nucleotide polymorphisms in the HIF‑1α gene and chemoradiotherapy of locally advanced rectal cancer

Authors:
- Birgitte Mayland Havelund
- Karen‑Lise Garm Spindler
- John Ploen
- Rikke Fredslund Andersen
- Anders Jakobsen
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Affiliations: Department of Oncology, Vejle Hospital, Vejle 7100, Denmark, Department of Biochemistry, Vejle Hospital, Vejle 7100, Denmark, Faculty of Health Sciences, Institute of Regional Health Services Research, University of Southern Denmark, Odense 5000, Denmark
Published online on: July 31, 2012 https://doi.org/10.3892/ol.2012.837
Pages: 1056-1060

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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.

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1.	FJ FlemingL PahlmanJR MonsonNeoadjuvant therapy in rectal cancerDis Colon Rectum54901912201110.1007/DCR.0b013e31820eeb3721654259
2.	A Habr-GamaRO PerezW NadalinLong-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survivalJ Gastrointest Surg99099200510.1016/j.gassur.2004.10.01015623449
3.	M MaasRG Beets-TanDM LambregtsWait-and-see policy for clinical complete responders after chemoradiation for rectal cancerJ Clin Oncol2946334640201110.1200/JCO.2011.37.717622067400
4.	AL HarrisHypoxia - a key regulatory factor in tumour growthNat Rev Cancer23847200210.1038/nrc70411902584
5.	LH GrayAD CongerM EbertS HornseyOC ScottThe concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapyBr J Radiol26638648195310.1259/0007-1285-26-312-63813106296
6.	GL WangBH JiangEA RueGL SemenzaHypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O₂ tensionProc Natl Acad Sci USA9255105514199510.1073/pnas.92.12.55107539918
7.	D VordermarkJM BrownEndogenous markers of tumour hypoxia predictors of clinical radiation resistance?Strahlenther Onkol179801811200310.1007/s00066-003-1150-914652668
8.	UR JewellI KvietikovaA ScheidC BauerRH WengerM GassmannInduction of HIF-1alpha in response to hypoxia is instantaneousFASEB J1513121314200111344124
9.	GL SemenzaDefining the role of hypoxia-inducible factor 1 in cancer biology and therapeuticsOncogene29625634201010.1038/onc.2009.44119946328
10.	A UnruhA ResselHG MohamedThe hypoxia-inducible factor-1 alpha is a negative factor for tumour therapyOncogene2232133220200310.1038/sj.onc.120638512761491
11.	KJ WilliamsBA TelferD XenakiEnhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1Radiother Oncol758998200510.1016/j.radonc.2005.01.00915878106
12.	BJ MoellerMW DewhirstHIF-1 and tumour radiosensitivityBr J Cancer9515200610.1038/sj.bjc.6603201
13.	R RavizzaR MolteniMB GariboldiE MarrasG PerlettiE MontiEffect of HIF-1 modulation on the response of two- and three-dimensional cultures of human colon cancer cells to 5-fluorouracilEur J Cancer45890898200910.1016/j.ejca.2008.12.02119171477
14.	BM HavelundFB SorensenJ LindebjergKL SpindlerA JakobsenPretreatment HIF-1α and GLUT-1 expressions do not correlate with outcome after preoperative chemoradiotherapy in rectal cancerAnticancer Res31155915652011
15.	E KorkeilaPM JaakkolaK SyrjanenJ SundstromS PyrhonenPreoperative radiotherapy downregulates the nuclear expression of hypoxia-inducible factor-1alpha in rectal cancerScand J Gastroenterol45340348201010.3109/0036552090348363520001759
16.	Y ToiyamaY InoueS SaigusaGene expression profiles of epidermal growth factor receptor, vascular endothelial growth factor and hypoxia-inducible factor-1 with special reference to local responsiveness to neoadjuvant chemoradiotherapy and disease recurrence after rectal cancer surgeryClin Oncol (R Coll Radiol)222722802010
17.	S SaigusaK TanakaY ToiyamaClinical significance of CD133 and hypoxia inducible factor-1α gene expression in rectal cancer after preoperative chemoradiotherapyClin Oncol (R Coll Radiol)23323332201120970309
18.	K TanimotoK YoshigaH EguchiHypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significanceCarcinogenesis2417791783200310.1093/carcin/bgg132
19.	MJ KangSA JungJM JungAssociations between single nucleotide polymorphisms of MMP2, VEGF, and HIF1A genes and the risk of developing colorectal cancerAnticancer Res31575584201121378341
20.	T KuwaiY KitadaiS TanakaSingle nucleotide polymorphism in the hypoxia-inducible factor-1alpha gene in colorectal carcinomaOncol Rep1210331037200415492789
21.	B FrankM HoffmeisterN KloppT IlligJ Chang-ClaudeH BrennerSingle nucleotide polymorphisms in Wnt signaling and cell death pathway genes and susceptibility to colorectal cancerCarcinogenesis3113811386201010.1093/carcin/bgq08220403915
22.	A JakobsenJP MortensenC BisgaardJ LindebjergJW HansenSR RafaelsenPreoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boostInt J Radiat Oncol Biol Phys64461465200610.1016/j.ijrobp.2005.07.96916226396
23.	A JakobsenJP MortensenC BisgaardJ LindebjergSR RafaelsenVO BendtsenA COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer: a phase II trialInt J Colorectal Dis23251255200810.1007/s00384-007-0407-718064474
24.	AKM JakobsenAL AppeltJ LindebjergJ PloeenSR RafaelsenT VuongThe dose-effect relationship in preoperative chemoradiation of locally advanced rectal cancer: Preliminary results of a phase III trialJ Clin Oncol (Meeting Abstracts)2935122011
25.	AM MandardF DalibardJC MandardPathologic assessment of tumour regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlationsCancer7326802686199410.1002/1097-0142(19940601)73:11%3C2680::AID-CNCR2820731105%3E3.0.CO;2-C
26.	K FransénM FenechM FredriksonC DabrosinP SöderkvistAssociation between ulcerative growth and hypoxia inducible factor-1alpha polymorphisms in colorectal cancer patientsMol Carcinog45833840200616865676
27.	XS FuE ChoiGJ BubleySP BalkIdentification of hypoxia-inducible factor-1alpha (HIF-1alpha) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradationProstate63215221200510.1002/pros.2019015538748
28.	G KnechtelJ SzkanderaM StotzSingle nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer riskMol Carcinog49805809201020572162
29.	DM AebersoldP BurriKT BeerJ LaissueV DjonovRH GreinerGL SemenzaExpression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancerCancer Res6129112916200111306467
30.	P SilvaNJ SlevinP SloanPrognostic significance of tumour hypoxia inducible factor-1alpha expression for outcome after radiotherapy in oropharyngeal cancerInt J Radiat Oncol Biol Phys7215511559200810.1016/j.ijrobp.2008.07.05119028277
31.	ML SchrijversBF van der LaanGH de BockOverexpression of intrinsic hypoxia markers HIF1alpha and CA-IX predict for local recurrence in stage T1-T2 glottic laryngeal carcinoma treated with radiotherapyInt J Radiat Oncol Biol Phys72161169200810.1016/j.ijrobp.2008.05.025
32.	B BachtiaryM SchindlR PotterOverexpression of hypoxia-inducible factor 1alpha indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancerClin Cancer Res9223422402003
33.	P BurriV DjonovDM AebersoldSignificant correlation of hypoxia-inducible factor-1alpha with treatment outcome in cervical cancer treated with radical radiotherapyInt J Radiat Oncol Biol Phys56494501200310.1016/S0360-3016(02)04579-012738326
34.	RM ChristleyPower and error: Increased risk of false positive results in underpowered studiesOpen Epidemiol J31619201010.2174/1874297101003010016