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CA-SSR1 Polymorphism in Intron 1 of the EGFR Gene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab.

Jarząbek T, Rucińska M, Rogowski W, Lewandowska M, Tujakowski J, Habib M, Kowalczyk A, Byszek A, Dziadziuszko R, Nawrocki S - Mol Diagn Ther (2015)

Bottom Line: The study included 60 patients treated with cetuximab.The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions.No statistically significant relationship between genotype and response to treatment was observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, University of Warmia and Mazury, Olsztyn, Poland.

ABSTRACT

Background and objective: Epidermal growth factor receptor (EGFR) inhibitors are not equally effective in all cancer patients. One potential clinical factor that could help in selecting patients who may benefit from treatment with cetuximab is acneiform rash, which correlates with the clinical response to EGFR inhibitors. Some previous studies have suggested that the tendency to develop rash may depend on polymorphisms in the EGFR gene. In this investigation, the association of degree of CA dinucleotide polymorphism with skin rash and cetuximab therapy outcome was examined.

Methods: The study included 60 patients treated with cetuximab. For each patient, the severity of acneiform rash was assessed, and the type of polymorphism was determined by genotyping. Associations between genotypes, the acneiform rash, and response to treatment were determined by using the chi-square test and Spearman's rank correlation. The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions.

Results: A correlation was found between body surface area covered by rash and the sum of the two allele repetitions (p=0.030). No statistically significant relationship between genotype and response to treatment was observed. However, in patients who have had partial remission, we noticed a higher incidence of polymorphism, with less CA dinucleotide repetitions and early onset of rash.

Conclusion: A correlation between genotype and severity of rash was observed. That is, the severity of rash decreased with an increased number of CA repetitions.

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Related in: MedlinePlus

Histogram presenting examination of the relationship between the response to treatment with cetuximab and CA-SSR1 genotype and the patient’s acneiform rash. a Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of two alleles, cutoff n(CA) ≤ 35, n(CA) > 35. b Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of a single allele cutoff S ≤ 17(CA), L > 17(CA). c Response to treatment with cetuximab (RECIST scale) vs. grouped NCI CTCAE v3.0 scale. d Response to treatment with cetuximab (RECIST scale) vs. the early grade 2–3 rash. A Spearman’s rank correlation was calculated for each relationship. In all cases, we did not obtain a statistically significant result. Dotted lines indicate the group characterized by the highest coefficient of variation. In patients with partial remission we observed a better response to cetuximab treatment when there was a smaller number of repetitions in the polymorphic region of CA-SSR1 of the EGFR gene and early grade 2–3 rash. CA-SSR1 CA simple sequence repeat in intron 1, L long allele, NCI CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Events, RECIST Response Evaluation Criteria In Solid Tumors, S short allele
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Fig3: Histogram presenting examination of the relationship between the response to treatment with cetuximab and CA-SSR1 genotype and the patient’s acneiform rash. a Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of two alleles, cutoff n(CA) ≤ 35, n(CA) > 35. b Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of a single allele cutoff S ≤ 17(CA), L > 17(CA). c Response to treatment with cetuximab (RECIST scale) vs. grouped NCI CTCAE v3.0 scale. d Response to treatment with cetuximab (RECIST scale) vs. the early grade 2–3 rash. A Spearman’s rank correlation was calculated for each relationship. In all cases, we did not obtain a statistically significant result. Dotted lines indicate the group characterized by the highest coefficient of variation. In patients with partial remission we observed a better response to cetuximab treatment when there was a smaller number of repetitions in the polymorphic region of CA-SSR1 of the EGFR gene and early grade 2–3 rash. CA-SSR1 CA simple sequence repeat in intron 1, L long allele, NCI CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Events, RECIST Response Evaluation Criteria In Solid Tumors, S short allele

Mentions: A weak correlation was found between severity of rash and response to treatment (p = 0.058), as shown in Fig. 3c. In patients with partial remission and stabilization, better response to treatment with cetuximab and early occurrence of rash were observed.Fig. 3


CA-SSR1 Polymorphism in Intron 1 of the EGFR Gene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab.

Jarząbek T, Rucińska M, Rogowski W, Lewandowska M, Tujakowski J, Habib M, Kowalczyk A, Byszek A, Dziadziuszko R, Nawrocki S - Mol Diagn Ther (2015)

Histogram presenting examination of the relationship between the response to treatment with cetuximab and CA-SSR1 genotype and the patient’s acneiform rash. a Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of two alleles, cutoff n(CA) ≤ 35, n(CA) > 35. b Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of a single allele cutoff S ≤ 17(CA), L > 17(CA). c Response to treatment with cetuximab (RECIST scale) vs. grouped NCI CTCAE v3.0 scale. d Response to treatment with cetuximab (RECIST scale) vs. the early grade 2–3 rash. A Spearman’s rank correlation was calculated for each relationship. In all cases, we did not obtain a statistically significant result. Dotted lines indicate the group characterized by the highest coefficient of variation. In patients with partial remission we observed a better response to cetuximab treatment when there was a smaller number of repetitions in the polymorphic region of CA-SSR1 of the EGFR gene and early grade 2–3 rash. CA-SSR1 CA simple sequence repeat in intron 1, L long allele, NCI CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Events, RECIST Response Evaluation Criteria In Solid Tumors, S short allele
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4555232&req=5

Fig3: Histogram presenting examination of the relationship between the response to treatment with cetuximab and CA-SSR1 genotype and the patient’s acneiform rash. a Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of two alleles, cutoff n(CA) ≤ 35, n(CA) > 35. b Response to treatment with cetuximab (RECIST scale) vs. the sum of CA repetitions of a single allele cutoff S ≤ 17(CA), L > 17(CA). c Response to treatment with cetuximab (RECIST scale) vs. grouped NCI CTCAE v3.0 scale. d Response to treatment with cetuximab (RECIST scale) vs. the early grade 2–3 rash. A Spearman’s rank correlation was calculated for each relationship. In all cases, we did not obtain a statistically significant result. Dotted lines indicate the group characterized by the highest coefficient of variation. In patients with partial remission we observed a better response to cetuximab treatment when there was a smaller number of repetitions in the polymorphic region of CA-SSR1 of the EGFR gene and early grade 2–3 rash. CA-SSR1 CA simple sequence repeat in intron 1, L long allele, NCI CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Events, RECIST Response Evaluation Criteria In Solid Tumors, S short allele
Mentions: A weak correlation was found between severity of rash and response to treatment (p = 0.058), as shown in Fig. 3c. In patients with partial remission and stabilization, better response to treatment with cetuximab and early occurrence of rash were observed.Fig. 3

Bottom Line: The study included 60 patients treated with cetuximab.The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions.No statistically significant relationship between genotype and response to treatment was observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, University of Warmia and Mazury, Olsztyn, Poland.

ABSTRACT

Background and objective: Epidermal growth factor receptor (EGFR) inhibitors are not equally effective in all cancer patients. One potential clinical factor that could help in selecting patients who may benefit from treatment with cetuximab is acneiform rash, which correlates with the clinical response to EGFR inhibitors. Some previous studies have suggested that the tendency to develop rash may depend on polymorphisms in the EGFR gene. In this investigation, the association of degree of CA dinucleotide polymorphism with skin rash and cetuximab therapy outcome was examined.

Methods: The study included 60 patients treated with cetuximab. For each patient, the severity of acneiform rash was assessed, and the type of polymorphism was determined by genotyping. Associations between genotypes, the acneiform rash, and response to treatment were determined by using the chi-square test and Spearman's rank correlation. The cutoffs S≤17(CA), L>17(CA), n(CA)≤35, and n(CA)>35 were tested, as well as the sum of the two allele repetitions.

Results: A correlation was found between body surface area covered by rash and the sum of the two allele repetitions (p=0.030). No statistically significant relationship between genotype and response to treatment was observed. However, in patients who have had partial remission, we noticed a higher incidence of polymorphism, with less CA dinucleotide repetitions and early onset of rash.

Conclusion: A correlation between genotype and severity of rash was observed. That is, the severity of rash decreased with an increased number of CA repetitions.

Show MeSH
Related in: MedlinePlus