Alcohol consumption and breast tumor mitochondrial DNA mutations.
Mitochondrial DNA (mtDNA) mutations are frequent in breast tumors, but the etiology of these mutations is unknown. We hypothesized that these mutations are associated with exposures that affect oxidative stress such as alcohol metabolism. Using archived tumor blocks from incident breast cancer cases in a case control study, the Western New York Exposures and Breast Cancer (WEB) study, analysis of mtDNA mutations was conducted on 128 breast cancer cases selected based on extremes of alcohol intake. Temporal temperature gradient gel electrophoresis (TTGE) was used to screen the entire mtDNA genome and sequencing was completed for all TTGE positive samples. Case-case comparisons were completed using unconditional logistic regression to determine the relative prevalence of the mutations by exposures including alcohol consumption, manganese superoxide dismutase (MnSOD) genotype, nutrient intake related to oxidative stress and established breast cancer risk factors. Somatic mtDNA mutations were found in 60 of the 128 tumors examined. There were no differences in the prevalence of mtDNA mutations by alcohol consumption, MnSOD genotype or dietary intake. The likelihood of mtDNA mutations was reduced among those with a positive family history for breast cancer (OR = 0.33, CI = 0.12-0.92), among postmenopausal women who used hormone replacement therapy (OR = 0.46, CI = 0.19-1.08, P = 0.08) and was increased for ER negative tumors (OR = 2.05, CI = 0.95-4.43, P = 0.07). Consistent with previous studies, we found that mtDNA mutations are a frequent occurrence in breast tumors. An understanding of the etiology of mtDNA mutations may provide insight into breast carcinogenesis.
Platek
Mary E
ME
Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, New York 14263, USA. mary.platek@roswellpark.org
Shields
Peter G
PG
Tan
Duanjun
D
Marian
Catalin
C
Bonner
Matthew R
MR
McCann
Susan E
SE
Nie
Jing
J
Wilding
Gregory E
GE
Ambrosone
Christine
C
Millen
Amy E
AE
Trevisan
Maurizio
M
Russell
Marcia
M
Nochajski
Thomas H
TH
Edge
Stephen B
SB
Winston
Janet
J
Freudenheim
Jo L
JL
D000428:Alcohol Drinking / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics
D004272:DNA, Mitochondrial; D013482:Superoxide Dismutase