Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

Xiang Lin Tan, Odilia Popanda, Christine B. Ambrosone, Silke Kropp, Irmgard Helmbold, Dietrich Von Fournier, Wulf Haase, Marie Luise Sautter-Bihl, Frederik Wenz, Peter Schmezer, Jenny Chang-Claude

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3±9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p interaction =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p interaction=0.06) . Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalBreast Cancer Research and Treatment
Volume97
Issue number3
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Genetic Polymorphisms
Radiotherapy
Breast Neoplasms
Skin
Weights and Measures
Radiation
Segmental Mastectomy
Ionizing Radiation
Haplotypes
Freezing
Sequence Analysis
Body Mass Index
Alleles
Genotype
Prospective Studies
Polymerase Chain Reaction
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Acute toxicity
  • Breast cancer
  • Polymorphism
  • Radiotherapy
  • TP53
  • p21

Cite this

Tan, Xiang Lin ; Popanda, Odilia ; Ambrosone, Christine B. ; Kropp, Silke ; Helmbold, Irmgard ; Von Fournier, Dietrich ; Haase, Wulf ; Sautter-Bihl, Marie Luise ; Wenz, Frederik ; Schmezer, Peter ; Chang-Claude, Jenny. / Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients. In: Breast Cancer Research and Treatment. 2006 ; Vol. 97, No. 3. pp. 255-262.
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abstract = "p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3±9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95{\%} CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95{\%} CI, 0.61-1.89) (p interaction =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p interaction=0.06) . Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association.",
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Tan, XL, Popanda, O, Ambrosone, CB, Kropp, S, Helmbold, I, Von Fournier, D, Haase, W, Sautter-Bihl, ML, Wenz, F, Schmezer, P & Chang-Claude, J 2006, 'Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients', Breast Cancer Research and Treatment, vol. 97, no. 3, pp. 255-262. https://doi.org/10.1007/s10549-005-9119-2

Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients. / Tan, Xiang Lin; Popanda, Odilia; Ambrosone, Christine B.; Kropp, Silke; Helmbold, Irmgard; Von Fournier, Dietrich; Haase, Wulf; Sautter-Bihl, Marie Luise; Wenz, Frederik; Schmezer, Peter; Chang-Claude, Jenny.

In: Breast Cancer Research and Treatment, Vol. 97, No. 3, 01.06.2006, p. 255-262.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

AU - Tan, Xiang Lin

AU - Popanda, Odilia

AU - Ambrosone, Christine B.

AU - Kropp, Silke

AU - Helmbold, Irmgard

AU - Von Fournier, Dietrich

AU - Haase, Wulf

AU - Sautter-Bihl, Marie Luise

AU - Wenz, Frederik

AU - Schmezer, Peter

AU - Chang-Claude, Jenny

PY - 2006/6/1

Y1 - 2006/6/1

N2 - p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3±9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p interaction =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p interaction=0.06) . Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association.

AB - p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3±9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p interaction =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p interaction=0.06) . Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association.

KW - Acute toxicity

KW - Breast cancer

KW - Polymorphism

KW - Radiotherapy

KW - TP53

KW - p21

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