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

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, i...

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Vydané v:	PloS one Ročník 14; číslo 6; s. e0217868
Hlavní autori:	Onyeaghala, Guillaume, Lane, John, Pankratz, Nathan, Nelson, Heather H., Thyagarajan, Bharat, Walcheck, Bruce, Anderson, Kristin E., Prizment, Anna E.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 05.06.2019 Public Library of Science (PLoS)
Predmet:	Aged Alcohol use Alleles Analysis Biology and Life Sciences Cancer Cancer research Cancer screening Case-Control Studies Confidence intervals Cytotoxicity Development and progression Diabetes Diagnosis Disease susceptibility Epidemiology Female Gene polymorphism Genes Genetic polymorphisms Genetic Predisposition to Disease Genetic transformation Genomes Health risk assessment Health risks Histocompatibility Antigens Class I - genetics Humans Immune response Immune system Immunosurveillance Intelligence gathering Internet Laboratories Levels Lymphocytes Major histocompatibility complex Male Medical prognosis Medicine and Health Sciences Methods MICA protein Microsatellite Repeats - genetics Pancreatic cancer Pancreatic Neoplasms - genetics Pathology Polymorphism Polymorphism, Genetic Population Population studies Population-based studies Proteins Public health Regression analysis Research and Analysis Methods Risk Factors Risk management Solubility Statistical analysis Transformation Tumor cells Tumors United States United States > US Minnesota
ISSN:	1932-6203, 1932-6203
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Shrnutí:	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. 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. 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). 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. 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0217868