SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival
Academic Article
Publication Date:
2017
Short description:
SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival / Mohelnikova-Duchonova, B; Strouhal, O; Hughes, Dj; Holcatova, I; Oliverius, M; Kala, Z; Campa, D; Rizzato, C; Canzian, F; Pezzilli, R; Talar-Wojnarowska, R; Malecka-Panas, E; Sperti, C; Zambon, Cf; Pedrazzoli, S; Fogar, P; Milanetto, Ac; Capurso, G; Delle Fave, G; Valente, R; Gazouli, M; Malleo, G; Lawlor, Rt; Strobel, O; Hackert, T; Giese, N; Vodicka, P; Vodickova, L; Landi, S; Tavano, F; Gioffreda, D; Piepoli, A; Pazienza, V; Mambrini, A; Pedata, M; Cantore, M; Bambi, F; Ermini, S; Funel, N; Lemstrova, R; Soucek, P. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:(2017). [10.1038/srep43812]
abstract:
Abstract
Background: Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated
with overall survival of pancreatic cancer patients, while variants in this gene may affect the
development risk of colorectal and prostate cancers. This study tested whether genetic
variability in SLC22A3 associates with pancreatic cancer risk and prognosis.
Methods: Twenty three single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene
sequence, promoter, and regulatory elements were genotyped in the discovery phase using
DNA samples from 245 pancreatic cancer patients and 442 healthy hospital-based controls
from the Czech Republic. SNPs associating with disease risk or with prognosis of the patients
were evaluated in the validation phase comprising 1,273 cases and 3,466 controls from the
PANcreatic Disease ReseArch (PANDoRA) consortium.
Results: In the discovery phase, three SNPs (rs2504938, rs9364554, and rs2457571) were
significantly associated with an increased risk of pancreatic cancer. Moreover, rs7758229 was
associated with an increased risk of metastatic disease, while rs512077 and rs2504956 were
associated with overall survival of pancreatic cancer patients. In the validation phase of these
significant results, only the association of rs2504938 with survival was observed: PDAC
patients carrying the rare genotype in rs2504938 had significantly worse overall survival than
the rest of the patients (p=0.002).
Conclusion: Common variation in the SLC22A3 gene is unlikely to significantly contribute to
pancreatic cancer development risk in general. The rs2504938 SNP in SLC22A3 is
significantly associated with an unfavorable prognosis for pancreatic cancer patients.
Additional study addressing the effect of this SNP on the molecular and clinical phenotype is
warranted.
Background: Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated
with overall survival of pancreatic cancer patients, while variants in this gene may affect the
development risk of colorectal and prostate cancers. This study tested whether genetic
variability in SLC22A3 associates with pancreatic cancer risk and prognosis.
Methods: Twenty three single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene
sequence, promoter, and regulatory elements were genotyped in the discovery phase using
DNA samples from 245 pancreatic cancer patients and 442 healthy hospital-based controls
from the Czech Republic. SNPs associating with disease risk or with prognosis of the patients
were evaluated in the validation phase comprising 1,273 cases and 3,466 controls from the
PANcreatic Disease ReseArch (PANDoRA) consortium.
Results: In the discovery phase, three SNPs (rs2504938, rs9364554, and rs2457571) were
significantly associated with an increased risk of pancreatic cancer. Moreover, rs7758229 was
associated with an increased risk of metastatic disease, while rs512077 and rs2504956 were
associated with overall survival of pancreatic cancer patients. In the validation phase of these
significant results, only the association of rs2504938 with survival was observed: PDAC
patients carrying the rare genotype in rs2504938 had significantly worse overall survival than
the rest of the patients (p=0.002).
Conclusion: Common variation in the SLC22A3 gene is unlikely to significantly contribute to
pancreatic cancer development risk in general. The rs2504938 SNP in SLC22A3 is
significantly associated with an unfavorable prognosis for pancreatic cancer patients.
Additional study addressing the effect of this SNP on the molecular and clinical phenotype is
warranted.
Iris type:
1.1 Articolo in rivista
Keywords:
pancreas; cancer; risk; polymorphisms; SLC22A3; survival
List of contributors:
Mohelnikova-Duchonova, B; Strouhal, O; Hughes, Dj; Holcatova, I; Oliverius, M; Kala, Z; Campa, D; Rizzato, C; Canzian, F; Pezzilli, R; Talar-Wojnarowska, R; Malecka-Panas, E; Sperti, C; Zambon, Cf; Pedrazzoli, S; Fogar, P; Milanetto, Ac; Capurso, G; Delle Fave, G; Valente, R; Gazouli, M; Malleo, G; Lawlor, Rt; Strobel, O; Hackert, T; Giese, N; Vodicka, P; Vodickova, L; Landi, S; Tavano, F; Gioffreda, D; Piepoli, A; Pazienza, V; Mambrini, A; Pedata, M; Cantore, M; Bambi, F; Ermini, S; Funel, N; Lemstrova, R; Soucek, P
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