title: CAG repeat variants in the POLG1 gene encoding mtDNA polymerase-gamma and risk of breast cancer in African-American women.
abstract: The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49-6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies.
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharine's, Ontario, Canada.
authors.forename: Sami
authors.initials: S
authors.lastname: Azrak
authors.forename: Vanniarajan
authors.initials: V
authors.lastname: Ayyasamy
authors.forename: Gary
authors.initials: G
authors.lastname: Zirpoli
authors.forename: Christine
authors.initials: C
authors.lastname: Ambrosone
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Dana H
authors.initials: DH
authors.lastname: Bovbjerg
authors.forename: Lina
authors.initials: L
authors.lastname: Jandorf
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pawlish
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.forename: Keshav
authors.initials: K
authors.lastname: Singh
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase