Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer

• Main Authors: Huang, Q. (Author), Li, J. (Author), Wu, H. (Author), Yu, Z. (Author), Zeng, J. (Author), Zhong, Z. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: adult; Adult; aged; Aged; Aged, 80 and over; Article; blood level; CA 242 antigen; cancer prognosis; cancer staging; carcinoembryonic antigen; clinical feature; colorectal cancer; Colorectal Neoplasms; colorectal tumor; dihydropyrimidine dehydrogenase; Dihydrouracil Dehydrogenase (NADP); distant metastasis; DPYD; DPYD gene; female; Female; genetic association; genetic predisposition; Genetic Predisposition to Disease; genetics; genotype; human; human tissue; Humans; lymph node metastasis; Lymphatic Metastasis; major clinical study; male; Male; middle aged; Middle Aged; mutation rate; pathology; polymerase chain reaction; Polymorphism, Single Nucleotide; retrospective study; risk factor; Risk Factors; Sanger sequencing; single nucleotide polymorphism; very elderly
• Online Access: View Fulltext in Publisher

 Background: Dihydropyrimidine dehydrogenase (DPD) acts as the key enzyme catabolizing pyrimidines, and may affect the tumor progression. DPYD gene mutations affect DPD activity. The relationship between DPYD IVS14+1G>A, c.1627A>G, c.85T>C and lymph node metastasis (LNM) and distant metastasis (DM) of colorectal cancer (CRC) was investigated. Methods: A total of 537 CRC patients were enrolled in this study. DPYD polymorphisms were analyzed by polymerase chain reaction (PCR)-Sanger sequencing. The relationship between DPYD genotypes and clinical features of patients, metastasis of CRC was analyzed. Results: About DPYD c.1627A>G, A/A (57.7%) was the most common genotype, followed by A/G (35.6%), G/G (6.7%) genotypes. In c.85T>C, T/T, T/C, and C/C genotypes are accounted for 83.6%, 16.0%, and 0.4%, respectively. Logistic regression analysis revealed that DPYD c.1627A>G A/G and G/G genotypes in the dominant model (A/G + G/G vs. A/A) were significant risk factors for the LNM (p = 0.029, OR 1.506, 95% CI = 1.048–2.165) and DM (p = 0.039, OR 1.588, 95% CI = 1.041–2.423) of CRC. In addition, DPYD c.1627A>G polymorphism was more common in patients with abnormal serum carcinoembryonic antigen (CEA) (>5 ng/ml) (p = 0.003) or carbohydrate antigen 24–2 (CA24-2) (>20 U/ml) level (p = 0.015). Conclusions: The results suggested that DPYD c.1627A>G A/G, G/G genotypes are associated with increased risk of LNM and DM of CRC. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.