Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk

PLoS One. 2013;8(1):e53768. doi: 10.1371/journal.pone.0053768. Epub 2013 Jan 16.


Background: The late endosomal LAMTOR complex serves as a convergence point for both the RAF/MEK/ERK and the PI3K/AKT/mTOR pathways. Interestingly, both of these signalling cascades play a significant role in the aetiology of breast cancer. Our aim was to address the possible role of genetic polymorphisms in LAMTOR2 and LAMTOR3 as genetic risk factors for breast cancer.

Methodology/results: We sequenced the exons and exon-intron boundaries of LAMTOR2 (p14) and LAMTOR3 (MP1) in 50 prospectively collected pairs of cancerous tissue and blood samples from breast cancer patients and compared their genetic variability. We found one single nucleotide polymorphism (SNP) in LAMTOR2 (rs7541) and two SNPs in LAMTOR3 (rs2298735 and rs148972953) in both tumour and blood samples, but no somatic mutations in cancerous tissues. In addition, we genotyped all three SNPs in 296 samples from the Risk Prediction of Breast Cancer Metastasis Study and found evidence of a genetic association between rs148972953 and oestrogen (ER) and progesterone receptor negative status (PR) (ER: OR = 3.60 (1.15-11.28); PR: OR = 4.27 (1.43-12.72)). However, when we additionally genotyped rs148972953 in the MARIE study including 2,715 breast cancer cases and 5,216 controls, we observed neither a difference in genotype frequencies between patients and controls nor was the SNP associated with ER or PR. Finally, all three SNPs were equally frequent in breast cancer samples and female participants (n = 640) of the population-based SAPHIR Study.

Conclusions: The identified polymorphisms in LAMTOR2 and LAMTOR3 do not seem to play a relevant role in breast cancer. Our work does not exclude a role of other not yet identified SNPs or that the here annotated polymorphism may in fact play a relevant role in other diseases. Our results underscore the importance of replication in association studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Computational Biology
  • Exons / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Middle Aged
  • Multiprotein Complexes / metabolism
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism


  • Adaptor Proteins, Signal Transducing
  • LAMTOR3 protein, human
  • Multiprotein Complexes
  • ragulator complex protein LAMTOR2, human
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Extracellular Signal-Regulated MAP Kinases

Grant support

The project was supported by the COMET Centre ONCOTYROL (which is funded by BMVIT, BMWFJ, the Tiroler-Zukunftsstiftung and the Styrian Business Promotion Agency), by the Innsbruck Medical University, by the Verein Sanitätsbetrieb Autonome Provinz-Bozen, by the Tiroler-Landeskrankenanstalten-GmbH (TILAK), and by the Sequencing & Genotyping Unit of the Innsbruck Medical University. Work in the Huber laboratory was supported by the FWF (Austria) funded special research program "cell proliferation and cell death in tumors"-SFB021. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.