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Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer.

ABSTRACT:

Background & aims

Insulin-like growth factor (IGF)-axis mediated signaling pathways play an important role in pancreatic cancer development and progression. We examined whether IGF-axis gene variants are associated with clinical outcomes in pancreatic cancer.

Methods

We retrospectively genotyped 41 single-nucleotide polymorphisms from 10 IGF-axis genes in 333 patients with localized pancreatic adenocarcinoma and validated the findings in 373 patients with advanced disease. Associations between genotype and overall survival (OS) were evaluated using multivariable Cox proportional hazard regression models.

Results

IGF1 *8470T>C, IGF1R IVS2+46329T>C, IGFBP3 A32G, IRS1 G972R in patients with localized disease; IGF1R IVS20-3431A>G, IGF1R T766T, IGFBP3-202A>C, IRS1 IVS1+4315C>G, IRS1 G972R in patients with advanced disease; and IGF1R T766T, IGF2R L252V, IGFBP3 -202A>C, IRS1 IVS1+4315C>G, IRS1 G972R, IRS2 IVS1+5687T>C in all patients were significantly associated with OS (PA, and an IRS2 haplotype predicted worse OS (PConclusionsThese data suggest that individual genetic variations in the IGF axis pathway may predict worse survival in patients with pancreatic cancer. This information may identify population subgroups that could benefit from IGF(1)R-targeted agents.

SUBMITTER: Dong X 

PROVIDER: S-EPMC2910789 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer.

Dong Xiaoqun X   Javle Milind M   Hess Kenneth R KR   Shroff Rachna R   Abbruzzese James L JL   Li Donghui D  

Gastroenterology 20100421 2

<h4>Background & aims</h4>Insulin-like growth factor (IGF)-axis mediated signaling pathways play an important role in pancreatic cancer development and progression. We examined whether IGF-axis gene variants are associated with clinical outcomes in pancreatic cancer.<h4>Methods</h4>We retrospectively genotyped 41 single-nucleotide polymorphisms from 10 IGF-axis genes in 333 patients with localized pancreatic adenocarcinoma and validated the findings in 373 patients with advanced disease. Associa  ...[more]

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