OBJECTIVE: Insulin-like growth factor (IGF)-axis genes plays a critical role in cancer development and progression via their impact on the RAS/MAPK/ERK and PI3K/AKT/mTOR signaling pathways. We hypothesized that IGF-axis genetic variants modify individual susceptibility to pancreatic cancer. METHODS: We retrospectively genotyped 41 single-nucleotide polymorphisms of 10 IGF-axis genes (IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS4) in 706 pancreatic cancer patients and 706 cancer-free controls using Sequenom and TaqMan technology. The association between genotype and pancreatic cancer risk was evaluated using multivariate logistic regression. A P value ≤.007 at a false discovery rate of 10% was set as the significance level. RESULTS: We observed that the IGF1 *10212C>A and Ex4+2776G>A and IGF1R IVS2-70184A>G and IVS2+46329T>C variant genotypes were significantly associated with decreased pancreatic cancer risk (odds ratio [OR] range, 0.60-0.75) and that IGFBP1 Ex4+111A>G (I253M) was significantly associated with increased pancreatic cancer risk (OR=1.46) after adjusted for other risk factors and multiple comparisons (P≤.007). IGF2R and IGFBP3 variant haplotypes were associated with increased and decreased pancreatic cancer risk, respectively (P<.001). We also observed a weak interaction of the IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes (P(interaction)=.05) and interaction of IGF2R and IRS1 genotypes with alcohol consumption (P(interaction)=.03 and .019, respectively) on increased pancreatic cancer risk. CONCLUSION: These findings support our hypothesis that polymorphic variants of IGF-axis genes act alone or jointly with other risk factors to affect susceptibility to pancreatic cancer. Copyright Â
OBJECTIVE: Insulin-like growth factor (IGF)-axis genes plays a critical role in cancer development and progression via their impact on the RAS/MAPK/ERK and PI3K/AKT/mTOR signaling pathways. We hypothesized that IGF-axis genetic variants modify individual susceptibility to pancreatic cancer. METHODS: We retrospectively genotyped 41 single-nucleotide polymorphisms of 10 IGF-axis genes (IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS4) in 706 pancreatic cancerpatients and 706 cancer-free controls using Sequenom and TaqMan technology. The association between genotype and pancreatic cancer risk was evaluated using multivariate logistic regression. A P value ≤.007 at a false discovery rate of 10% was set as the significance level. RESULTS: We observed that the IGF1 *10212C>A and Ex4+2776G>A and IGF1R IVS2-70184A>G and IVS2+46329T>C variant genotypes were significantly associated with decreased pancreatic cancer risk (odds ratio [OR] range, 0.60-0.75) and that IGFBP1 Ex4+111A>G (I253M) was significantly associated with increased pancreatic cancer risk (OR=1.46) after adjusted for other risk factors and multiple comparisons (P≤.007). IGF2R and IGFBP3 variant haplotypes were associated with increased and decreased pancreatic cancer risk, respectively (P<.001). We also observed a weak interaction of the IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes (P(interaction)=.05) and interaction of IGF2R and IRS1 genotypes with alcohol consumption (P(interaction)=.03 and .019, respectively) on increased pancreatic cancer risk. CONCLUSION: These findings support our hypothesis that polymorphic variants of IGF-axis genes act alone or jointly with other risk factors to affect susceptibility to pancreatic cancer. Copyright Â
Authors: J M Genkinger; M Wang; R Li; D Albanes; K E Anderson; L Bernstein; P A van den Brandt; D R English; J L Freudenheim; C S Fuchs; S M Gapstur; G G Giles; R A Goldbohm; N Håkansson; P L Horn-Ross; A Koushik; J R Marshall; M L McCullough; A B Miller; K Robien; T E Rohan; C Schairer; D T Silverman; R Z Stolzenberg-Solomon; J Virtamo; W C Willett; A Wolk; R G Ziegler; S A Smith-Warner Journal: Ann Oncol Date: 2014-03-14 Impact factor: 32.976
Authors: Miguel A Ortega; Leonel Pekarek; Cielo Garcia-Montero; Oscar Fraile-Martinez; Miguel A Saez; Angel Asúnsolo; Miguel A Alvarez-Mon; Jorge Monserrat; Santiago Coca; M Val Toledo-Lobo; Natalio García-Honduvilla; Agustin Albillos; Julia Buján; Melchor Alvarez-Mon; Luis G Guijarro Journal: Histol Histopathol Date: 2022-02-09 Impact factor: 2.303
Authors: David T Chao; Nilesh H Shah; Herbert J Zeh; Nathan Bahary; David C Whitcomb; Randall E Brand Journal: Pancreas Date: 2016-02 Impact factor: 3.327