55979558 Missense Subs. GTA â ATA V [Val] â I [Ile] rs7667298 KDR. 4. 55991731 5'UTR. -. - rs307805 FLT4. 5. 180077487 Prom; TFBS. -. - rs6877011 FLT4.
Università Politecnica delle Marche AOU Ospedali Riuniti “Umberto I – GM Lancisi – G Salesi” Department of Medical Oncology Ancona - Italy
Correlation between VEGF and VEGF-R polymorphisms, toxicity and clinical outcome in HCC patients receiving sorafenib. L u c a F a l o p p i 1 , M a r i o S c a r t o z z i 1 , M a r i s t e l l a B i a n c o n i 1 , C r i s t i a n L o re t e l l i 1 , G i a n l u c a S v e g l i a t i B a ro n i 2 , S a m u e l e D e M i n i c i s 2 , A l e s s a n d r a M a n d o l e s i 3 , R i c c a r d o G i a m p i e r i 1 , A l e s s a n d ro B i t t o n i 1 , M i c h e l a D e l P re t e 1 , L u c a C e c c h i n i 1 , I t a l o B e a r z i 3 , A n t o n i o B e n e d e t t i 2 , S t e f a n o C a s c i n u 1 . 1) Department of Medical Oncology 2) Clinica di Gastroenterologia 2) Institute of Pathology – AOU Ospedali Riuniti - UNIVPM, Ancona, Italy.
Gene
Chromosome
Chromosome Position
VEGFA
6
43753212
3'UTR
-
-
rs2010963 VEGFA
6
43738350
5'UTR
-
-
rs25648
VEGFA
6
43738977
Syn; ESE
TCCà TCT S [Ser] àS [Ser]
rs3025039 VEGFA
6
43752536
3'UTR
-
-
rs699947
VEGFA
6
43736389
promoter
-
-
rs833061
VEGFA
6
43737486
promoter
-
-
rs4604006 VEGFC
4
177608775 intronic
-
-
rs7664413 VEGFC
4
177608707 intronic
-
-
rs664393
FLT1
13
29071001
3'UTR
-
-
rs7993418 rs1870377
FLT1 KDR
13 4
28883061 55972974
Syn; ESE Missense Subs.
TAC à TAT Y [Tyr] à Y [Tyr] CAAà CAT Q [Gln]à H [His]
rs2071559
KDR
4
55992366
Init. Transcription -
rs2305948
KDR
4
55979558
Missense Subs.
GTA à ATA V [Val] à I [Ile]
rs7667298
KDR
4
55991731
5'UTR
-
-
rs307805
FLT4
5
180077487 Prom; TFBS
-
-
rs6877011
FLT4
5
180029471 3'UTR
-
-
rs307822
FLT4
5
180028717 3'UTR
-
-
Background
were significantly associated with any grade global (respectively: p=0.031;
The introduction of sorafenib for the treatment of advanced HCC radically
p=0.018; p=0.003) and cutaneous toxicities (respectively: p=0.043; p=0.019;
rs10434
changed patients’ clinical outcome. However response to treatment as well as
p=0.025). Furthermore patients with any grade global and cutaneous
toxicity are still largely unpredictable in the single patient. We previously
toxicities showed a better progression free survival and overall survival
reported that VEGF and VEGFR polymorphisms may have a predictive and
(global toxicity PFS: 7.0 vs 5.0 months, p=0.016; OS: 26.8 vs 13.0 months,
prognostic role in this setting, but little is known about the possible
p=0.023) (cutaneous toxicity PFS: 7.6 vs 5.1 months, p=0.033; OS: 22.7 vs 13.3
correlation with toxicity.
months, p=0.014)
The aim of our study was to evaluate whether VEGF and VEGFR genotyping
Conclusions
was able to correlate with toxicity in HCC patients receiving sorafenib.
In our analysis patients with polymorphism T at rs833061, C at rs699947 and
Methods
C at rs2010963 showed a higher rate of toxicities and, accordingly to our
73 histological samples of HCC patients receiving sorafenib were tested for
previous report, this correlates with a better PFS and OS. Analysis of VEGF
VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms
and its receptor genes polymorphisms represents a clinical tool to identify
(SNPs). Patients time to progression (TTP), overall survival (OS) and
patients with favourable response to sorafenib presumably related to a more
toxicities were analysed.
efficient control of tumour growth. The occurrence of toxicity could be an
Results
interesting clinical surrogate during sorafenib treatment and may help
VEGF-A rs833061 T>C, rs699947 C>A and rs2010963 C>G polymorphisms
clinicians in a more cautious and aware management of HCC patients.
Figure 1 PFS according to global toxicity (any grade).
Poster: Q10
Correspondence to:
Any grade toxicity Global Rash Hand-foot
Figure 2 OS according to global toxicity (any grade).
Nausea/vomiting Diarrhea Fatigue Liver dysfunction
N 33 8 13 5 14 10 2
% 45 11 18 6 19 14 3
Figure 3 PFS according to cutaneous toxicity (any grade).
SNP ID
Position in the gene / Effect
Codon Exchange
Aminoacid Exchange
-
syn: Synonymous substitution; ESE: Exon Splicing Enhancer; 3’UTR: Untranslated Region 3'UTR; 5’UTR: Untranslated Region 5'UTR; Prom: Promoter region; TFBS: Predicted Trascription Factor Binding Site.
Figure 4 OS according to cutaneous toxicity (any grade).
L u c a F a l o p p i M D – U N I V P M C l i n i c a d i O n c o l o g i a M e d i c a – Vi a Tr o n t o 1 0 – 6 0 1 2 6 A n c o n a – I t a l y – e m a i l : l u c a f a l o p p i @ g m a i l . c o m
