Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk
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Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk. / De Araujo, Mariana E; Erhart, Gertraud; Buck, Katharina; Müller-Holzner, Elisabeth; Hubalek, Michael; Fiegl, Heidelinde; Campa, Daniele; Canzian, Federico; Eilber, Ursula; Chang-Claude, Jenny; Coassin, Stefan; Haun, Margot; Kedenko, Lyudmyla; Paulweber, Bernhard; Reitsamer, Roland; Himmel, Irmgard; Flesch-Janys, Dieter; Lamina, Claudia; Kronenberg, Florian; Huber, Lukas A; Kloss-Brandstätter, Anita.
In: PLOS ONE, Vol. 8, No. 1, 01.01.2013, p. e53768.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk
AU - De Araujo, Mariana E
AU - Erhart, Gertraud
AU - Buck, Katharina
AU - Müller-Holzner, Elisabeth
AU - Hubalek, Michael
AU - Fiegl, Heidelinde
AU - Campa, Daniele
AU - Canzian, Federico
AU - Eilber, Ursula
AU - Chang-Claude, Jenny
AU - Coassin, Stefan
AU - Haun, Margot
AU - Kedenko, Lyudmyla
AU - Paulweber, Bernhard
AU - Reitsamer, Roland
AU - Himmel, Irmgard
AU - Flesch-Janys, Dieter
AU - Lamina, Claudia
AU - Kronenberg, Florian
AU - Huber, Lukas A
AU - Kloss-Brandstätter, Anita
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Computational Biology
KW - Exons
KW - Extracellular Signal-Regulated MAP Kinases
KW - Female
KW - Genetic Predisposition to Disease
KW - Humans
KW - Middle Aged
KW - Multiprotein Complexes
KW - Mutation
KW - Polymorphism, Single Nucleotide
KW - Signal Transduction
KW - TOR Serine-Threonine Kinases
U2 - 10.1371/journal.pone.0053768
DO - 10.1371/journal.pone.0053768
M3 - SCORING: Journal article
C2 - 23341997
VL - 8
SP - e53768
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 1
ER -
