Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk.
OBJECTIVE
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.
Department of Epidemiology, University of North Carolina, CB #7435, McGavran-Greenberg Hall, Chapel Hill, NC 27599-7435, USA. lauren.mccullough@unc.edu
Lauren E
LE
McCullough
Regina M
RM
Santella
Rebecca J
RJ
Cleveland
Patrick T
PT
Bradshaw
Robert C
RC
Millikan
Kari E
KE
North
Andrew F
AF
Olshan
Sybil M
SM
Eng
Christine B
CB
Ambrosone
Jiyoung
J
Ahn
Susan E
SE
Steck
Susan L
SL
Teitelbaum
Alfred I
AI
Neugut
Marilie D
MD
Gammon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult