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Can genes for mammographic density inform cancer aetiology?

Nature Reviews Cancer volume 8, pages 812–823 (2008)Cite this article

Abstract

Mammographic density (MD) reflects variations in fat, stromal and epithelial tissues that are thought to be regulated by several genes. High MD is an established risk factor for breast cancer; therefore, genes that regulate MD may indirectly influence breast cancer. These genes might also be fewer in number and easier to identify than those for breast cancer risk outside of inherited predisposition syndromes. In this Perspective, we review the limited genetic studies of MD and propose future directions.

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Figure 1: The insulin-like growth factor (IGF) axis.
Figure 2: Pathways of steroid hormone synthesis, metabolism and sensitivity of tissues.

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Acknowledgements

National Cancer Institute Grants R01 CA97396, R01 CA128931 and P50 CA116201

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Authors and Affiliations

  1. Linda E. Kelemen is at the Department of Population Health Research, Alberta Cancer Board, 1,331 29th Street North West, Calgary, Alberta T2N 4N2, Canada.,

    Linda E. Kelemen

  2. Thomas A. Sellers is at the H. Lee Moffitt Cancer Center & Research Institute, 12,902 Magnolia Drive, Tampa, Florida 33612, USA.,

    Thomas A. Sellers

  3. Celine M. Vachon is at the Department of Health Sciences Research, College of Medicine. Mayo Clinic, 200 First Street South West, Rochester, Minnesota 55905, USA.,

    Celine M. Vachon

Authors
  1. Linda E. Kelemen
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  2. Thomas A. Sellers
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  3. Celine M. Vachon
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Corresponding author

Correspondence to Celine M. Vachon.

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DATABASES

National Cancer Institute

breast cancer

National Cancer Institute Drug Dictionary

 tamoxifen

FURTHER INFORMATION

Breast Cancer Information Core

Glossary

Familial aggregation

A tendency for a trait to occur or cluster in multiple family members more often than would be expected by chance.

Genetic association studies

Tests whether a polymorphism in a candidate gene explains the inter-individual variation in a trait under study.

Haplotype blocks

Configurations of alleles within regions on the chromosome that tend to be inherited together (that is, are in high linkage disequilibrium). Little genetic variability is observed within this region among individuals in a population.

Linkage analysis

The process of determining the approximate chromosomal location of a gene associated with the trait being studied by looking for evidence of co-segregation with other marker genes whose locations are already known.

Linkage disequilibrium

Non-random association of alleles at two or more loci on chromosomes in a population, beyond that expected by chance.

Parent–offspring and twin studies

Investigates the proportion of variation in the trait under study that is explained by unmeasured additive genetic factors among respective relative pairs.

Segregation analysis

Tests hypotheses about whether the existence of major genes account for the observed pattern of familial aggregation of the trait and provides evidence for the mode of inheritance of the genes using pedigree data. Statistical models compare Mendelian inheritance patterns of a trait to a model in which there are no restrictions on mode of inheritance or other model parameters.

Stroma

The supportive framework of a biological tissue with an extensive extracellular matrix that serves to support cells, separate tissues and regulate intercellular communication.

Tag single nucleotide polymorphisms

(tagSNPs). A reduced set of single nucleotide polymorphisms that identify or 'tag' other SNPs with which it is in high linkage disequilibrium.

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Kelemen, L., Sellers, T. & Vachon, C. Can genes for mammographic density inform cancer aetiology?. Nat Rev Cancer 8, 812–823 (2008). https://doi.org/10.1038/nrc2466

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