TY - JOUR
T1 - Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women
AU - Gong, Zhihong
AU - Yao, Song
AU - Zirpoli, Gary
AU - David Cheng, Ting Yuan
AU - Roberts, Michelle
AU - Khoury, Thaer
AU - Ciupak, Gregory
AU - Davis, Warren
AU - Pawlish, Karen
AU - Jandorf, Lina
AU - Bovbjerg, Dana H.
AU - Bandera, Elisa V.
AU - Ambrosone, Christine B.
N1 - Publisher Copyright:
© 2015 UICC.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - African American
KW - European American
KW - breast cancer
KW - one-carbon metabolism
KW - polymorphisms
UR - https://www.scopus.com/pages/publications/84929502453
U2 - 10.1002/ijc.29434
DO - 10.1002/ijc.29434
M3 - Article
C2 - 25598430
AN - SCOPUS:84929502453
SN - 0020-7136
VL - 137
SP - 666
EP - 677
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 3
ER -