Abstract
BackgroundPancreatic cancer is the third leading cause of cancer related deaths in the United States. Several dietary factors have been identified that modify pancreatic cancer risk, including low folate levels. In addition to nutrition and lifestyle determinants, folate status may be influenced by genetic factors such as single nucleotide polymorphisms (SNPs). In the present study, we investigated the association between folate levels, genetic polymorphisms in genes of the folate pathway, and pancreatic cancer.MethodsSerum and red blood cell (RBC) folate levels were measured in pancreatic cancer and control subjects. Genotypes were determined utilizing Taqman probes and SNP frequencies between cases and controls were assessed using Fisher’s exact test. Logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence intervals (CIs) to measure the association between genotypes and pancreatic cancer risk. The association between folate levels and SNP expression was calculated using one-way ANOVA.ResultsMean RBC folate levels were significantly lower in pancreatic cancer cases compared to unrelated controls (508.4 ± 215.9 ng/mL vs 588.3 ± 229.2 ng/mL, respectively) whereas serum folate levels were similar. Irrespective of cancer status, several SNPs were found to be associated with altered serum folate concentrations, including the D919G SNP in methionine synthase (MTR), the L474F SNP in serine hydroxymethyl transferase 1 (SHMT1) and the V175M SNP in phosphatidyl ethanolamine methyltransferase (PEMT). Further, the V allele of the A222V SNP and the E allele of the E429A SNP in methylene tetrahydrofolate reductase (MTHFR) were associated with low RBC folate levels. Pancreatic cancer risk was found to be significantly lower for the LL allele of the L78R SNP in choline dehydrogenase (CHDH; OR = 0.29; 95% CI 0.12–0.76); however, it was not associated with altered serum or RBC folate levels.
Highlights
Pancreatic cancer, the third leading cause of cancer deaths in the United States, is an aggressive cancer with median 5 year survival rates of only 8% [1]
Irrespective of cancer status, several single nucleotide polymorphisms (SNPs) were found to be associated with altered serum folate concentrations, including the D919G SNP in methionine synthase (MTR), the L474F SNP in serine hydroxymethyl transferase 1 (SHMT1) and the valine at position 175 in PEMT (V175M) SNP in phosphatidyl ethanolamine methyltransferase (PEMT)
Folate and pancreatic cancer risk (CHDH; odds ratio (OR) = 0.29; 95% confidence intervals (CIs) 0.12–0.76); it was not associated with altered serum or red blood cell (RBC) folate levels
Summary
Pancreatic cancer, the third leading cause of cancer deaths in the United States, is an aggressive cancer with median 5 year survival rates of only 8% [1]. In the age of personalized medicine, identification of genetic and environmental factors that affect the risk for development of pancreatic cancer may aid in prevention or lead to increased surveillance of susceptible individuals. Risk of development of various cancer types in humans, including pancreatic cancer, has been shown to increase with low dietary folate intake [6,7,8,9]. Pancreatic cancer is the third leading cause of cancer related deaths in the United States. Several dietary factors have been identified that modify pancreatic cancer risk, including low folate levels. We investigated the association between folate levels, genetic polymorphisms in genes of the folate pathway, and pancreatic cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
