Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast

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 & 6 others Louise A. Brinton, Anna Maria Storniolo, Chunyan He, Stephen J. Chanock, Gretchen L. Gierach, Jonine D. Figueroa

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)825-832
Number of pages8
JournalInternational Journal of Cancer
Volume140
Issue number4
DOIs
StatePublished - Feb 15 2017

Fingerprint

Genetic Predisposition to Disease
Single Nucleotide Polymorphism
Breast
Breast Neoplasms
Alleles
Genome-Wide Association Study
Confidence Intervals
Neoplasms

Keywords

  • breast cancer
  • genetic susceptibility
  • involution
  • terminal duct lobular unit

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Bodelon, C., Oh, H., Chatterjee, N., Garcia-Closas, M., Palakal, M., Sherman, M. E., ... Figueroa, J. D. (2017). Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast. International Journal of Cancer, 140(4), 825-832. https://doi.org/10.1002/ijc.30512

Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast. / Bodelon, Clara; Oh, Hannah; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Palakal, Maya; Sherman, Mark E.; Pfeiffer, Ruth M.; Geller, Berta M.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Papathomas, Daphne; Xiang, Jackie; Patel, Deesha A.; Khodr, Zeina G.; Linville, Laura; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Brinton, Louise A.; Storniolo, Anna Maria; He, Chunyan; Chanock, Stephen J.; Gierach, Gretchen L.; Figueroa, Jonine D.

In: International Journal of Cancer, Vol. 140, No. 4, 15.02.2017, p. 825-832.

Research output: Contribution to journalArticle

Bodelon, C, Oh, H, Chatterjee, N, Garcia-Closas, M, Palakal, M, Sherman, ME, Pfeiffer, RM, Geller, BM, Vacek, PM, Weaver, DL, Chicoine, RE, Papathomas, D, Xiang, J, Patel, DA, Khodr, ZG, Linville, L, Clare, SE, Visscher, DW, Mies, C, Hewitt, SM, Brinton, LA, Storniolo, AM, He, C, Chanock, SJ, Gierach, GL & Figueroa, JD 2017, 'Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast', International Journal of Cancer, vol. 140, no. 4, pp. 825-832. https://doi.org/10.1002/ijc.30512
Bodelon, Clara ; Oh, Hannah ; Chatterjee, Nilanjan ; Garcia-Closas, Montserrat ; Palakal, Maya ; Sherman, Mark E. ; Pfeiffer, Ruth M. ; Geller, Berta M. ; Vacek, Pamela M. ; Weaver, Donald L. ; Chicoine, Rachael E. ; Papathomas, Daphne ; Xiang, Jackie ; Patel, Deesha A. ; Khodr, Zeina G. ; Linville, Laura ; Clare, Susan E. ; Visscher, Daniel W. ; Mies, Carolyn ; Hewitt, Stephen M. ; Brinton, Louise A. ; Storniolo, Anna Maria ; He, Chunyan ; Chanock, Stephen J. ; Gierach, Gretchen L. ; Figueroa, Jonine D. / Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast. In: International Journal of Cancer. 2017 ; Vol. 140, No. 4. pp. 825-832.
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T1 - Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast

AU - Bodelon, Clara

AU - Oh, Hannah

AU - Chatterjee, Nilanjan

AU - Garcia-Closas, Montserrat

AU - Palakal, Maya

AU - Sherman, Mark E.

AU - Pfeiffer, Ruth M.

AU - Geller, Berta M.

AU - Vacek, Pamela M.

AU - Weaver, Donald L.

AU - Chicoine, Rachael E.

AU - Papathomas, Daphne

AU - Xiang, Jackie

AU - Patel, Deesha A.

AU - Khodr, Zeina G.

AU - Linville, Laura

AU - Clare, Susan E.

AU - Visscher, Daniel W.

AU - Mies, Carolyn

AU - Hewitt, Stephen M.

AU - Brinton, Louise A.

AU - Storniolo, Anna Maria

AU - He, Chunyan

AU - Chanock, Stephen J.

AU - Gierach, Gretchen L.

AU - Figueroa, Jonine D.

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