Association of CYP24A1 gene polymorphism with colorectal cancer in the Jiamusi population

PLoS One. 2021 Jun 30;16(6):e0253474. doi: 10.1371/journal.pone.0253474. eCollection 2021.

Abstract

Background: The population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility.

Method: A case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed.

Results: Overall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09-3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08-2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03-6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25-4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99-3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92-17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00-23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10-3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05-4.77).

Conclusion: CYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • China
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Female
  • Gastrointestinal Absorption / genetics
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase / genetics*
  • Vitamin D3 24-Hydroxylase / metabolism

Substances

  • Vitamin D
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase

Grants and funding

This work was supported by grants from by the Natural Science Foundation of China (71490732, 9184910151,81849132,81400790,81460203,3176029,81571385,91849132,81872096); National Key Research and Development Program of China (2018YFC2000400); Guangxi Natural Science Foundation (2014GXNSFDA118028, 2018GXNSFAA138156, guike0991198); Self-funded Scientific Research Project of the health and family planning commission of Guangxi Zhuang Autonomous Region (Z20170162); Beijing Hospital Nova Project (BJ-2018-139); Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC330003).