Abstract Background: Recent reports support an association between chronic inflammation and progression to pancreatic cancer (PC). Methods: This case–control, candidate gene association study evaluated 1,354 Caucasian patients with pancreatic ductal adenocarcinoma and 1,189 healthy Caucasian controls. We genotyped 1,538 single nucleotide polymorphism (SNP) in 102 genes from inflammatory pathways involving NF-κB. Primary tests of association assumed a multiplicative (log-additive) genotype effect; secondary analyses examined dominant, additive, and recessive SNP effects. Results: After adjusting for known risk factors for PC, single SNP analysis revealed an association between four SNPs in NOS1 and one in the CD101 gene with PC risk. These results, however, were not replicated in a PC case–control and cohort population. Conclusion:NOS1 and CD101 may be associated with a risk of PC; however, these findings did not replicate in other PC populations. Future research is needed into the possible role of NOS1 and CD101 for PC. Impact: This research shows a lack of association between genetic variation in 102 inflammation-related genes and PC. Future research is needed into the possible role of other inflammation-related genes and PC risk. Cancer Epidemiol Biomarkers Prev; 20(6); 1251–4. ©2011 AACR.