Abstract 1219: Association between MICA polymorphisms, s-MICA levels, and pancreatic cancer risk in a population-based case-control study

Abstract

Abstract Objectives: The immune system has been shown to play an important role in pancreatic cancer. Abnormal cells express the transmembrane major histocompatibility complex class I chain-related gene A (MICA) protein, which is recognized by receptors present on NK and cytotoxic T cells. However, pancreatic tumor cells release MICA protein in soluble form (called s-MICA) from the tumor surface and thus avoid immune surveillance. In our previous study, we showed that a higher serum concentration of the s-MICA protein was associated with increased pancreatic cancer risk. In the current study, we hypothesized that functional variants in the MICA gene are associated with higher circulating s-MICA levels and increased pancreatic cancer risk. We focused on the A5.1 MICA allele, as this allele encodes a MICA protein that is shorter than its normal counterpart and is more easily cleaved from the cell surface. Methods: MICA alleles and s-MICA levels were measured in 116 cases and 492 controls (n=608) in a population-based case-control study in Minnesota. Allele assignments were based on the number of repeat units in the amplified regions of the MICA gene, and s-MICA levels were measured by enzyme-linked immunoabsorbent assay. To address the non-normal distribution of s-MICA levels, general linear regression with a log link was used to assess mean s-MICA levels across MICA alleles. Unconditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for pancreatic cancer after adjustment for age, sex, education, smoking status, alcohol consumption, and diabetes status. The analysis was restricted to Caucasians, who represented 96% of all study participants. Results: 452 participants (74%) possessed at least one copy of the A5.1 allele. After adjustment for confounders, participants with at least one copy of the MICA A5.1 allele were at an increased risk of pancreatic cancer (multivariable OR=2.00, 95% CI: 1.06-3.79), compared to participants who did not possess any A5.1 allele. Participants who had at least one copy of the A5.1 allele had 2.46 (95%CI: 2.36-2.56) times greater mean s-MICA levels than those without the A5.1 allele. These associations were consistent among pancreatic cancer cases and controls. Conclusions: Our study supports the role of the MICA A5.1 allele in impaired immune response, which may increase the risk of pancreatic cancer. Citation Format: Guillaume C. Onyeaghala, John Lane, Nathan Pankratz, Heather H. Nelson, Bharat Thyagarajan, Kristin E. Anderson, Anna E. Prizment. Association between MICA polymorphisms, s-MICA levels, and pancreatic cancer risk in a population-based case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1219.