title: Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast.
abstract: Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution. Poisson regression models with robust variance were used to calculate adjusted per-allele relative risks (with the non-breast cancer risk allele as the referent) and 95% confidence intervals between TDLU measures and each SNP. All statistical tests were two-sided; P < 0.05 was considered statistically significant. Overall, 36 SNPs (58.1%) were related to higher TDLU counts although this was not statistically significant (p = 0.25). Six of the 62 SNPs (9.7%) were nominally associated with at least one TDLU measure: rs616488 (PEX14), rs11242675 (FOXQ1) and rs6001930 (MKL1) were associated with higher TDLU count (p = 0.047, 0.045 and 0.031, respectively); rs1353747 (PDE4D) and rs6472903 (8q21.11) were associated with higher acini count per TDLU (p = 0.007 and 0.027, respectively); and rs1353747 (PDE4D) and rs204247 (RANBP9) were associated with the product of TDLU and acini counts (p = 0.024 and 0.017, respectively). Our findings suggest breast cancer SNPs may not strongly influence TDLU involution. Agnostic genome-wide association studies of TDLU involution may provide new insights on its biologic underpinnings and breast cancer susceptibility.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Clara
authors.initials: C
authors.lastname: Bodelon
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Hannah
authors.initials: H
authors.lastname: Oh
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Maya
authors.initials: M
authors.lastname: Palakal
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.|Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: The University of Vermont, Burlington, VT.
authors.forename: Berta
authors.initials: B
authors.lastname: Geller
authors.affiliation: The University of Vermont, Burlington, VT.
authors.forename: Pamela
authors.initials: P
authors.lastname: Vacek
authors.affiliation: The University of Vermont, Burlington, VT.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.affiliation: The University of Vermont, Burlington, VT.
authors.forename: Rachael
authors.initials: R
authors.lastname: Chicoine
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Daphne
authors.initials: D
authors.lastname: Papathomas
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Jackie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Zeina G
authors.initials: ZG
authors.lastname: Khodr
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Laura
authors.initials: L
authors.lastname: Linville
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Clare
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Mies
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, IN.
authors.forename: Anna Maria V
authors.initials: AMV
authors.lastname: Storniolo
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.|Usher Institute of Population Health Sciences and Informatics and Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D042361:Mammary Glands, Human / Q000648:ultrastructure*; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D011795:Surveys and Questionnaires; D055815:Young Adult
keywords: breast cancer; genetic susceptibility; involution; terminal duct lobular unit