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


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.
Division of Cell Biology, Innsbruck Medical University, Innsbruck, Austria.
Mariana E
ME
De Araujo
Gertraud
G
Erhart
Katharina
K
Buck
Elisabeth
E
Müller-Holzner
Michael
M
Hubalek
Heidelinde
H
Fiegl
Daniele
D
Campa
Federico
F
Canzian
Ursula
U
Eilber
Jenny
J
Chang-Claude
Stefan
S
Coassin
Margot
M
Haun
Lyudmyla
L
Kedenko
Bernhard
B
Paulweber
Roland
R
Reitsamer
Irmgard
I
Himmel
Dieter
D
Flesch-Janys
Claudia
C
Lamina
Florian
F
Kronenberg
Lukas A
LA
Huber
Anita
A
Kloss-Brandstätter
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019295:Computational Biology; D005091:Exons / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C485425:LAMTOR3 protein, human; D046912:Multiprotein Complexes; C577278:LAMTOR2 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases