VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
G. Lurje ◽  
A. M. Schultheis ◽  
A. E. Hendifar ◽  
S. Ashouri ◽  
W. Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vegf Receptor ◽  
Stage Iii Colon Cancer ◽  
Increased Risk

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.

scholarly journals The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

2010 ◽  
Vol 21 (12) ◽  
pp. 2396-2402 ◽  
Author(s):  
A. Fariña-Sarasqueta ◽  
G. van Lijnschoten ◽  
E. Moerland ◽  
G.-J. Creemers ◽  
V.E.P.P. Lemmens ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Braf V600e Mutation ◽  
Independent Prognostic Factor ◽  
Stage Ii ◽  
Braf V600e ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

The effect of gaps in chemotherapy on survival in patients with high-risk stage II and stage III colon cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 180-180
Author(s):  
Yvonne Sada ◽  
Zhigang Duan ◽  
Hashem El-Serag ◽  
Jessica Davila
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Factors ◽  
Stage Iii Colon Cancer ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Multivariable Regression ◽  
The Impact

180 Background: Current guidelines recommend six months of chemotherapy (CT) for stage III colon cancer and consideration for high-risk stage II colon cancer. No previous studies have examined the impact of CT gaps on survival. This retrospective study examines determinants of CT gaps and the effect of gaps on survival. Methods: Using national Surveillance, Epidemiology, and End Results registry-Medicare linked data, high-risk stage II and stage III colon cancer patients diagnosed between 2000-2007 who received surgery and CT were identified. CT duration and gaps were calculated. CT gap was defined as 30 to 90 days between two CT claims. Data on demographics, clinical factors (comorbidity, tumor grade), and treatment factors (time to CT initiation, toxicity, hospitalization) were collected. Multivariable regression was used to examine factors associated with gaps. Cox proportional hazards analysis examined the effect of gaps on risk of mortality. Results: 7,371 patients were identified. Median age was 75 (IQR: 71-79); 47% were male. Among all patients, 1,803 (24%) had a gap. 2,674 patients (36%) received 5 to 7 months of CT, of which 469 (18%) had a gap. Multivariable regression analysis showed that patients who were black (OR 1.3, 95% CI: 1.1-1.7), stage III (1.2, 1.0-1.3), had toxicity (1.3, 1.1-1.4), or had 3 to 4 months of CT (vs. 5-7 months, 2.6, 2.3-3.0) were more likely to have a gap, while patients with a more recent diagnosis in 2007(vs. 2000, 0.6, 0.5-0.8) were less likely to have a gap. 3-year cancer-specific survival was the same in all patients with CT gaps compared with no gaps (80%, 95% CI: 78%-82% vs. 81%, 95% CI: 80%-82%). Cox proportional hazard models showed that patients with gaps did not have increased risk of mortality (HR 0.99, 0.89-1.1) adjusting for patient and clinical factors. Among those who received 5 to 7 months of CT, 3-year survival was 8% lower in patients with gaps compared to those with no gaps (80%, 95% CI: 75%-83% vs. 88%, 95% CI: 87%-90%). Conclusions: Nearly 25% of high-risk stage II and III patients who received CT had a gap. CT gaps were associated with worse survival in patients who received 5 to 7 months of CT. Interventions to improve CT toxicity management and reduce gaps are needed to maximize the benefit of CT.

Integrin genetic variants and stage-specific tumor recurrence in patients with stage II and III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3604-3604
Author(s):  
Pierre Oliver Bohanes ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
Melissa Janae Labonte ◽  
Armin Gerger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Nucleotide Polymorphisms ◽  
Direct Dna Sequencing ◽  
Cancer Dormancy

3604 Background: Integrins are key elements in cancer biology regulating tumor growth, angiogenesis and lymphangiogenesis through interactions of the tumor cells with the microenvironment. Recent evidence showing that integrins are critical in cancer dormancy suggests that their differential expression or activity may be responsible for tumor recurrence. Moving from the hypothesis that integrins could have different effects in stage II and III colon cancer, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in integrin genes could predict stage-specific time to tumor recurrence (TTR) in stage II and III colon cancer patients. Methods: A total of 234 patients, 105 high-risk stage II and 129 stage III, treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. The median follow-up time was 4.4 years. Whole blood samples were analyzed for 22 germline SNPs in integrin genes using PCR-RFLP or direct DNA-sequencing. Results: In the multivariate analysis,stage II colon cancer patients with at least one G allele for ITGB3 rs4642 had higher risk of recurrence (HR=4.027, 95%CI 1.556-10.421, p=0.004). This association was also significant in the combined stage II-III cohort (HR=1.975, HR 95%CI 1.194-3.269, p=0.008). The predominant role of ITGB3 rs4642 in stage II diseases was confirmed using recursive partitioning, showing that ITGB3 rs4642 was the most important factor in stage II diseases. In contrast, in stage III diseases, both ITGB1 rs2298141 (HR=1.909, 95%CI 1.054-3.459, p=0.033) and ITGA4 rs7562325 (HR=0.227, 95%CI 0.064-0.804, p=0.022) were associated with TTR. The latter showed a significant interaction between stages (p=0.048). Conclusions: This study identifies germline polymorphisms in integrin genes as independent stage-specific prognostic markers for stage II and III colon cancer. These data strengthen the role of tumor dormancy in early colon cancer and may help to select subgroups of patients who may benefit from integrin-targeted treatments.

VEGF and VEGFR1 gene expression levels and tumor recurrence in adjuvant colon cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Y. Ning ◽  
G. Lurje ◽  
K. Danenberg ◽  
J. Cooc ◽  
D. Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Tissue Samples ◽  
Expression Levels ◽  
Stage Iii Colon Cancer ◽  
Gene Expression Levels

4040 Background: Tumor recurrence after curative resection is still a major problem in the management of adjuvant colon cancer, with recurrence rate approximately 30–40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. Our group previously showed that angiogenesis gene polymorphisms (VEGF and IL-8) may associated with tumor recurrence in adjuvant colon cancer (Lurje Ann Oncol, 2008). Here we tested the hypothesis whether gene expression levels of angiogenesis pathway (COX-2, EGFR, VEGF, VEGFR1, VEGFR2 and IL-8) could also predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Tissue samples from 140 adjuvant colon cancer patients (69 females and 71 males with a median age of 59 years; range=28–86) were available for gene expression assays. These tissue samples were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) and LAC+USC medical center between 1999 and 2006. Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. mRNA was extracted from laser-capture-microdissected tumor tissue. After cDNA was prepared by reverse transcription, quantitation of the candidate genes and an internal reference gene (ß-actin) was performed using a fluorescence-based real-time detection method (TaqMan). Results: We found VEGF and VEGFR1 gene expression levels independently significantly associated with time to tumor recurrence in adjuvant colon cancer patients. Patients with lower VEGF gene expression and lower VEGFR1 gene expression levels had significantly longer time to tumor recurrence compared to those with higher VEGF and higher VEGFR1 gene expression levels (p<0.05, log-rank test). Conclusions: VEGF and VEGFR1 gene expression levels may predict tumor recurrence risk in adjuvant colon cancer patients. Our exploratory data warrant future confirmatory trial. [Table: see text]

Association of genetic variants in plastin family genes with tumor recurrence in stage II/III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14031-e14031
Author(s):  
Yan Ning ◽  
Thomas Winder ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Stage Ii ◽  
In Vivo Studies ◽  
Actin Binding ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Log Rank Test

e14031 Background: Plastins belong to a subclass of actin-binding proteins known as actin bundling proteins. Plastins family constitute of two isoforms in human as T-plastin (PLS3) and L-plastin (LCP1). Recent in vitro and in vivo studies found plastin genes are overexpressed in colon cancer cells and can lead to increased proliferation, invasion and metastasis. Here we tested the hypothesis whether potential functional tagging polymorphisms in PLS3 (rs6643869, rs5987947, rs2522188) and LCP1 (rs4941543, rs1409429, rs11342) may predict tumor recurrence in adjuvant colon cancer patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. PLS3 and LCP1 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariable analysis, PLS3 rs6643869 and LCP1 rs4941543 were significantly associated with time to tumor recurrence (TTR). Patients with PLS3 AA genotype had shortest median TTR 3.2 years (95% C.I: 1.5-10.7) compared to those with AG or GG genotype, which had median TTR 9.4 years (95% C.I: 5.7-12.2) (p=0.012, log-rank test). Patients with LCP1 CC genotype had longer median TTR 10.7 years (95% C.I: 5.7-16.8+) compared to those with CT and TT genotypes, which had shorter median TTR 4.9 years (95% C.I: 1.4-9.0+)(p=0.040, log-rank test). PLS3 rs6643869 remained significant in the multivariate Cox regression model adjusted by stage and type of adjuvant therapy and stratified by race (p=0.021). Conclusions: Our preliminary results demonstrated that polymorphisms in plastin family genes PLS3 and LCP1 might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.

Prediction of tumor recurrence by tumor location in stage II and III colon cancer patients through common germ-line variants of genes involved in wnt signaling pathway.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14714-e14714
Author(s):  
Wu Zhang ◽  
Yan Ning ◽  
Dongyun Yang ◽  
Takeru Wakatsuki ◽  
Sebastian Stintzing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Wnt Signaling ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Tumor Recurrence ◽  
Wnt Signaling Pathway ◽  
Tumor Location ◽  
Stage Ii ◽  
Comprehensive Cancer Center ◽  
Tcf7l2 Rs7903146

e14714 Background: Wnt signaling is essential for embryonic development, stem cells and tissue regeneration. The Wnt signaling pathway was found to be deregulated in 93% of colorectal cancer (CRC). Tumor recurrence after curative resection is still a major problem in the management of adjuvant CRC, with recurrence rate approximately 30-40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. In this study, our group tested whether gene polymorphisms [TCF7L2 rs7903146, AXIN2 (rs2240308, rs3923087) and P300 (rs7286979, rs220551 and rs5782022)] involved in Wnt signaling pathway could predict the risk of tumor recurrence in stage II and III CRC patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. TCF7L2, AXIN2 and p300 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariate analysis, patients with TCF7L2 rs7903146 TT genotype had significantly longer TTR (median=10.7 months, 95%CI 4.9,10.7 +) compared with those harboring CT (median=3.9months, 95% CI 2.4, 10.7) or CC genotype (median=5.9months, 95% CI 2.8, 11.4+) patients (p=0.042, log-rank test). In multivariate analysis, left-side tumor patients with p300 rs7286979 AA genotype had highest risk of TTR (HR=2.85, 95% CI 1.03,7.89) compared to those carring GA (HR=0.81, 95% CI 0.35,1.84) or AA genotype (p=0.048, Wald test). Conclusions: Our results show that germline polymorphisms profiling of Wnt signaling pathway TCF7L2 rs7903146, p300 rs7286979 may predict tumor recurrence risk in adjuvant colon cancer patients, and may dependent on tumor location. Our exploratory data warrants further validation.

Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer

2008 ◽  
Vol 18 (2) ◽  
pp. 161-168 ◽  
Author(s):  
Georg Lurje ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Susan Groshen ◽  
Andrew E. Hendifar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Thymidylate Synthase ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer

scholarly journals Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients

Oncotarget ◽  
2016 ◽  
Vol 7 (45) ◽  
pp. 73876-73887 ◽  
Author(s):  
Evert van den Broek ◽  
Oscar Krijgsman ◽  
Daoud Sie ◽  
Marianne Tijssen ◽  
Sandra Mongera ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Stage Ii ◽  
Stage Iii ◽  
Genomic Profiling ◽  
Stage Iii Colon Cancer ◽  
Colon Cancers ◽  
Apc Mutations
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