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Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk

Purpose: The mechanisms driving the physical activity— breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidativ... Full description

Journal Title: Cancer Causes & Control 2012, Vol.23(12), pp.1949-1958
Main Author: McCullough, Lauren
Other Authors: Santella, Regina , Cleveland, Rebecca , Bradshaw, Patrick , Millikan, Robert , North, Kari , Olshan, Andrew , Eng, Sybil , Ambrosone, Christine , Ahn, Jiyoung , Steck, Susan , Teitelbaum, Susan , Neugut, Alfred , Gammon, Marilie
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0957-5243 ; E-ISSN: 1573-7225 ; DOI: 10.1007/s10552-012-0072-1
Link: http://dx.doi.org/10.1007/s10552-012-0072-1
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recordid: springer_jour10.1007/s10552-012-0072-1
title: Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk
format: Article
creator:
  • McCullough, Lauren
  • Santella, Regina
  • Cleveland, Rebecca
  • Bradshaw, Patrick
  • Millikan, Robert
  • North, Kari
  • Olshan, Andrew
  • Eng, Sybil
  • Ambrosone, Christine
  • Ahn, Jiyoung
  • Steck, Susan
  • Teitelbaum, Susan
  • Neugut, Alfred
  • Gammon, Marilie
subjects:
  • Breast cancer
  • Epidemiology
  • Catalase
  • Physical activity
  • Oxidative stress
ispartof: Cancer Causes & Control, 2012, Vol.23(12), pp.1949-1958
description: Purpose: The mechanisms driving the physical activity— breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity—breast cancer association. Methods: We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls. Results: Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59—0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06—2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38—0.84). Conclusions: Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.
language: eng
source:
identifier: ISSN: 0957-5243 ; E-ISSN: 1573-7225 ; DOI: 10.1007/s10552-012-0072-1
fulltext: fulltext
issn:
  • 1573-7225
  • 15737225
  • 0957-5243
  • 09575243
url: Link


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titlePolymorphisms in oxidative stress genes, physical activity, and breast cancer risk
creatorMcCullough, Lauren ; Santella, Regina ; Cleveland, Rebecca ; Bradshaw, Patrick ; Millikan, Robert ; North, Kari ; Olshan, Andrew ; Eng, Sybil ; Ambrosone, Christine ; Ahn, Jiyoung ; Steck, Susan ; Teitelbaum, Susan ; Neugut, Alfred ; Gammon, Marilie
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Purpose: The mechanisms driving the physical activity— breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity—breast cancer association. Methods: We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls. Results: Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59—0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06—2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38—0.84). Conclusions: Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation.

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authorMcCullough, Lauren ; Santella, Regina ; Cleveland, Rebecca ; Bradshaw, Patrick ; Millikan, Robert ; North, Kari ; Olshan, Andrew ; Eng, Sybil ; Ambrosone, Christine ; Ahn, Jiyoung ; Steck, Susan ; Teitelbaum, Susan ; Neugut, Alfred ; Gammon, Marilie
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