TY - JOUR
T1 - Differences in Genome-wide DNA Methylation Profiles in Breast Milk by Race and Lactation Duration
AU - Davis Lynn, Brittny C.
AU - Bodelon, Clara
AU - Pfeiffer, Ruth M.
AU - Yang, Hannah P.
AU - Yang, Howard H.
AU - Lee, Maxwell
AU - Laird, Peter W.
AU - Campan, Mihaela
AU - Weisenberger, Daniel J.
AU - Murphy, Jeanne
AU - Sampson, Joshua N.
AU - Browne, Eva P.
AU - Anderton, Douglas L.
AU - Sherman, Mark E.
AU - Arcaro, Kathleen F.
AU - Gierach, Gretchen L.
N1 - Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black (n = 57) and white (n = 82) women, ages 19–44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction (P < 1.63 X 10-7). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence.
AB - Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black (n = 57) and white (n = 82) women, ages 19–44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction (P < 1.63 X 10-7). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence.
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U2 - 10.1158/1940-6207.CAPR-19-0169
DO - 10.1158/1940-6207.CAPR-19-0169
M3 - Article
C2 - 31481539
AN - SCOPUS:85074444724
SN - 1940-6207
VL - 12
SP - 781
EP - 789
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 11
ER -