Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast |
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| Authors: | Clara Bodelon Hannah Oh Nilanjan Chatterjee Montserrat Garcia‐Closas Maya Palakal Mark E. Sherman Ruth M. Pfeiffer Berta M. Geller Pamela M. Vacek Donald L. Weaver Rachael E. Chicoine Daphne Papathomas Jackie Xiang Deesha A. Patel Zeina G. Khodr Laura Linville Susan E. Clare Daniel W. Visscher Carolyn Mies Stephen M. Hewitt Louise A. Brinton Anna Maria Storniolo Chunyan He Stephen J. Chanock Jonine D. Figueroa |
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| Affiliation: | 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;2. Division of Cancer Prevention, National Cancer Institute, Bethesda, MD;3. Department of Biostatistics, University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA;4. Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL;5. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN;6. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;7. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD;8. Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, IN;9. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN |
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| 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. |
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| Keywords: | genetic susceptibility terminal duct lobular unit involution breast cancer |
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