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Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer.
Clin Cancer Res 2006; 12(23):7063-70CC

Abstract

PURPOSE

Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity.

EXPERIMENTAL DESIGN

Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose.

RESULTS

Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), >25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (>25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI <25, and for MPO, those with high BMI (>25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI <25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women.

CONCLUSIONS

Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment.

Authors+Show Affiliations

Division of Cancer Prevention and Population Science, Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17145829

Citation

Ahn, Jiyoung, et al. "Polymorphisms in Genes Related to Oxidative Stress (CAT, MnSOD, MPO, and eNOS) and Acute Toxicities From Radiation Therapy Following Lumpectomy for Breast Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 12, no. 23, 2006, pp. 7063-70.
Ahn J, Ambrosone CB, Kanetsky PA, et al. Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer. Clin Cancer Res. 2006;12(23):7063-70.
Ahn, J., Ambrosone, C. B., Kanetsky, P. A., Tian, C., Lehman, T. A., Kropp, S., ... Chang-Claude, J. (2006). Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 12(23), pp. 7063-70.
Ahn J, et al. Polymorphisms in Genes Related to Oxidative Stress (CAT, MnSOD, MPO, and eNOS) and Acute Toxicities From Radiation Therapy Following Lumpectomy for Breast Cancer. Clin Cancer Res. 2006 Dec 1;12(23):7063-70. PubMed PMID: 17145829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms in genes related to oxidative stress (CAT, MnSOD, MPO, and eNOS) and acute toxicities from radiation therapy following lumpectomy for breast cancer. AU - Ahn,Jiyoung, AU - Ambrosone,Christine B, AU - Kanetsky,Peter A, AU - Tian,Chunqiao, AU - Lehman,Teresa A, AU - Kropp,Silke, AU - Helmbold,Irmgard, AU - von Fournier,Dietrich, AU - Haase,Wulf, AU - Sautter-Bihl,Marie Luise, AU - Wenz,Frederik, AU - Chang-Claude,Jenny, PY - 2006/12/6/pubmed PY - 2007/12/6/medline PY - 2006/12/6/entrez SP - 7063 EP - 70 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 12 IS - 23 N2 - PURPOSE: Because radiotherapy exerts cytotoxic effects via generation of massive oxidative stress, we hypothesized that catalase, manganese superoxide dismutase, myeloperoxidase (MPO), and endothelial nitric oxide synthase (eNOS) genotypes might result in greater risk of radiotoxicity. EXPERIMENTAL DESIGN: Cases (n = 446) were Caucasian women with breast cancer who received radiotherapy following lumpectomy. Genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight. The development of acute reactions (moist desquamation) associated with genotypes was modeled using the Cox proportional hazards model, accounting for cumulative biologically effective radiation dose. RESULTS: Genotypes associated with higher levels of reactive oxygen species (ROS) were not associated with risk of radiotoxicity. However, relationships between overweight/obesity [body mass index (BMI), >25] and radiotoxicity risk seemed to be modified by eNOS and MPO genotypes associated with higher generation of nitric oxide and ROS, respectively. Women with high BMI (>25) and eNOS GG genotypes were at more than a 6-fold increase in risk (hazard ratio, 6.39; 95% confidence interval, 2.53-16.15) compared with those with BMI <25, and for MPO, those with high BMI (>25) and GG genotypes also had greater risk of radiotoxicity (hazard ratio, 3.61; 95% confidence interval, 1.78-7.35) compared with those with BMI <25. Overweight/obesity was not a strong risk factor among women with other eNOS and MPO genotypes. Exploratory analysis using classification and regression trees indicated that total number of risk alleles contributed, in part, to acute toxicity outcomes among a subgroup of women. CONCLUSIONS: Associations between BMI and radiotoxicity risk may be most apparent among women with genotypes related to higher levels of oxidative stress. Regression trees may be useful in future studies to examine the contributions of multiple factors to individual susceptibility to adverse effects of cancer treatment. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17145829/Polymorphisms_in_genes_related_to_oxidative_stress__CAT_MnSOD_MPO_and_eNOS__and_acute_toxicities_from_radiation_therapy_following_lumpectomy_for_breast_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=17145829 DB - PRIME DP - Unbound Medicine ER -