Abstract
The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05-0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014-0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77-26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population.
| Original language | English |
|---|---|
| Pages (from-to) | 817-823 |
| Number of pages | 7 |
| Journal | European Journal of Human Genetics |
| Volume | 23 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 15 2015 |
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ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Folate-related polymorphisms in gastrointestinal stromal tumours : susceptibility and correlation with tumour characteristics and clinical outcome. / Angelini, Sabrina; Ravegnini, Gloria; Nannini, Margherita; Bermejo, Justo Lorenzo; Musti, Muriel; Pantaleo, Maria A.; Fumagalli, Elena; Venturoli, Nicola; Palassini, Elena; Consolini, Nicola; Casali, Paolo G.; Biasco, Guido; Hrelia, Patrizia.
In: European Journal of Human Genetics, Vol. 23, No. 6, 15.06.2015, p. 817-823.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Folate-related polymorphisms in gastrointestinal stromal tumours
T2 - susceptibility and correlation with tumour characteristics and clinical outcome
AU - Angelini, Sabrina
AU - Ravegnini, Gloria
AU - Nannini, Margherita
AU - Bermejo, Justo Lorenzo
AU - Musti, Muriel
AU - Pantaleo, Maria A.
AU - Fumagalli, Elena
AU - Venturoli, Nicola
AU - Palassini, Elena
AU - Consolini, Nicola
AU - Casali, Paolo G.
AU - Biasco, Guido
AU - Hrelia, Patrizia
PY - 2015/6/15
Y1 - 2015/6/15
N2 - The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05-0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014-0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77-26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population.
AB - The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05-0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014-0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77-26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population.
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U2 - 10.1038/ejhg.2014.198
DO - 10.1038/ejhg.2014.198
M3 - Article
VL - 23
SP - 817
EP - 823
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 6
ER -