BackgroundAsbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM.Subjects and methodsIn total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis.ResultsWe found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050).ConclusionsOur findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

e24074 Background: Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases that are involved in tissue remodeling. They can regulate interactions of cells with extracellular matrix and can play a role in wound healing. High levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies. The aim of our present study was to evaluate the association of MMP9 and MMP14 genetic polymorphisms with long-term complications of surgical treatment in breast cancer patients. Methods: The study included 99 breast cancer patients treated with either 75 or 37.5 mg of tramadol for pain relief after axillary breast cancer surgery as part of a randomized clinical trial KCT 04/2015-DORETAonko/si at Institute of Oncology Ljubljana. All patients were genotyped for MMP9 polymorphisms rs2250889, rs17577, rs17576, and rs20544 as well as MMP14 rs1042703, rs1042704, and rs743257. The association of genetic factors with long-term complications was evaluated using logistic regression. Results: One year after surgery, 24 (24.2%) patients had lymphedema, 25 (25.3%) experienced neuropathic pain and 21 (21.1%) experienced chronic pain. Carriers of polymorphic MMP9 rs2250889 allele experienced significantly more lymphedema compared to carriers of two wild-type alleles (OR = 3.45, 95% CI = 1.10-10.84, P = 0.034), even after adjustment for tramadol dose (OR = 3.76, 95% CI = 1.16-12.18, P = 0.027). Carriers of polymorphic MMP14 rs1042704 allele experienced more neuropathic pain compared to carriers of two wild-type alleles (OR = 3.21, 95% CI = 1.26-8.20, P = 0.015), even after adjustment for tramadol dose (OR = 3.80, 95% CI = 1.42-10.17, P = 0.008). Conclusions: MMP genetic variability was associated with long-term complications after axillary surgery in breast cancer patients, suggesting that MMPs may have an important role as modulators of wound healing.