TY - JOUR
T1 - Association between MICA polymorphisms, s-MICA levels, and pancreatic cancer risk in a population-based case-control study
AU - Onyeaghala, Guillaume
AU - Lane, John
AU - Pankratz, Nathan
AU - Nelson, Heather H.
AU - Thyagarajan, Bharat
AU - Walcheck, Bruce
AU - Anderson, Kristin E.
AU - Prizment, Anna E.
N1 - Publisher Copyright:
© 2019 Onyeaghala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/6
Y1 - 2019/6
N2 - Background Pancreatic tumor cells may avoid immune surveillance by releasing the transmembrane major histocompatibility complex class I chain-related A (MICA) protein in soluble form (s-MICA). We hypothesized that the presence of the A5.1 polymorphism in the MICA gene, which encodes a truncated MICA protein, is associated with higher s-MICA levels and increased pancreatic cancer risk. Methods MICA alleles and s-MICA levels were measured in 121 pancreatic cancer cases and 419 controls. General linear regression with a log transformation assessed geometric means of 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 associated with MICA alleles. Results After multivariate adjustment, participants with at least one copy of the A5.1 allele versus no A5.1 allele had 1.35 (95% CI: 1.05–1.74) times greater s-MICA levels (1.65 times higher for cases and 1.28, for controls) and increased risk of pancreatic cancer (OR = 1.91, 95% CI: 1.05–3.48). Conclusions Our study suggests higher risk of pancreatic cancer among those with the MICA A5.1 polymorphism, which may be explained by an increase in s-MICA secretion and impaired immune response. Impact These findings provide further evidence at the genetic and molecular level of the important role of MICA in pancreatic cancer development, and may have important implications with regards to pancreatic cancer screening.
AB - Background Pancreatic tumor cells may avoid immune surveillance by releasing the transmembrane major histocompatibility complex class I chain-related A (MICA) protein in soluble form (s-MICA). We hypothesized that the presence of the A5.1 polymorphism in the MICA gene, which encodes a truncated MICA protein, is associated with higher s-MICA levels and increased pancreatic cancer risk. Methods MICA alleles and s-MICA levels were measured in 121 pancreatic cancer cases and 419 controls. General linear regression with a log transformation assessed geometric means of 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 associated with MICA alleles. Results After multivariate adjustment, participants with at least one copy of the A5.1 allele versus no A5.1 allele had 1.35 (95% CI: 1.05–1.74) times greater s-MICA levels (1.65 times higher for cases and 1.28, for controls) and increased risk of pancreatic cancer (OR = 1.91, 95% CI: 1.05–3.48). Conclusions Our study suggests higher risk of pancreatic cancer among those with the MICA A5.1 polymorphism, which may be explained by an increase in s-MICA secretion and impaired immune response. Impact These findings provide further evidence at the genetic and molecular level of the important role of MICA in pancreatic cancer development, and may have important implications with regards to pancreatic cancer screening.
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U2 - 10.1371/journal.pone.0217868
DO - 10.1371/journal.pone.0217868
M3 - Article
C2 - 31166958
AN - SCOPUS:85066814931
SN - 1932-6203
VL - 14
JO - PloS one
JF - PloS one
IS - 6
M1 - e0217868
ER -