title: Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women.
abstract: Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299 African-American (AA) women who participated in the Women's Circle of Health Study. Allele frequencies varied significantly between EA and AA populations. A number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS and SLC19A1, were associated with overall breast cancer risk, as well as risk by estrogen receptor (ER) status, in either EA or AA women. Associations appeared to be modified by dietary folate intake. Although single-SNP associations were not statistically significant after correcting for multiple comparisons, polygenetic score analyses revealed significant associations with breast cancer risk. Per unit increase of the risk score was associated with a modest 19 to 50% increase in risk of breast cancer overall, ER positive or ER negative cancer (all p < 0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing gene polymorphisms could play a role in breast cancer and that may differ between EA and AA women.
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Gary
authors.initials: G
authors.lastname: Zirpoli
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Ting-Yuan
authors.initials: TY
authors.lastname: David Cheng
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.|Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY.
authors.forename: Michelle
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.affiliation: New Jersey State Cancer Registry, New Jersey Department of Health, Trenton, NJ.
authors.forename: Karen
authors.initials: K
authors.lastname: Pawlish
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Lina
authors.initials: L
authors.lastname: Jandorf
authors.affiliation: Department of Psychiatry, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
authors.forename: Dana H
authors.initials: DH
authors.lastname: Bovbjerg
authors.affiliation: Department of Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.|Department of Nutritional Sciences, Rutgers School of Public Health, Piscataway, NJ.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D004032:Diet; D005060:Europe / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011960:Receptors, Estrogen / Q000235:genetics; D012306:Risk; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D001741:Black or African American
chemical_list: D011960:Receptors, Estrogen; D005492:Folic Acid
keywords: African American; European American; breast cancer; one-carbon metabolism; polymorphisms