Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer
Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activat...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/11/6/978 |
| _version_ | 1797532173209698304 |
|---|---|
| author | Bei-Hao Shiu Ming-Hong Hsieh Wen-Chien Ting Ming-Chih Chou Lun-Ching Chang Chi-Chou Huang Shih-Chi Su Shun-Fa Yang |
| author_facet | Bei-Hao Shiu Ming-Hong Hsieh Wen-Chien Ting Ming-Chih Chou Lun-Ching Chang Chi-Chou Huang Shih-Chi Su Shun-Fa Yang |
| author_sort | Bei-Hao Shiu |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of <i>FGFR4</i> gene polymorphisms on the risk and progression of CRC. Three <i>FGFR4</i> single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; <i>p</i> = 0.046) or rs351855 (GA and AA; AOR, 0.191; <i>p</i> = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression. |
| first_indexed | 2024-03-10T10:55:21Z |
| format | Article |
| id | doaj.art-2c2d76076de249fb899a534de1488951 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T10:55:21Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-2c2d76076de249fb899a534de14889512023-11-21T21:52:20ZengMDPI AGDiagnostics2075-44182021-05-0111697810.3390/diagnostics11060978Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal CancerBei-Hao Shiu0Ming-Hong Hsieh1Wen-Chien Ting2Ming-Chih Chou3Lun-Ching Chang4Chi-Chou Huang5Shih-Chi Su6Shun-Fa Yang7Institute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanDepartment of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USAInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanWhole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 402, TaiwanColorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of <i>FGFR4</i> gene polymorphisms on the risk and progression of CRC. Three <i>FGFR4</i> single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; <i>p</i> = 0.046) or rs351855 (GA and AA; AOR, 0.191; <i>p</i> = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.https://www.mdpi.com/2075-4418/11/6/978colorectal cancerfibroblast growth factor receptor 4single-nucleotide polymorphismmetastasis |
| spellingShingle | Bei-Hao Shiu Ming-Hong Hsieh Wen-Chien Ting Ming-Chih Chou Lun-Ching Chang Chi-Chou Huang Shih-Chi Su Shun-Fa Yang Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer Diagnostics colorectal cancer fibroblast growth factor receptor 4 single-nucleotide polymorphism metastasis |
| title | Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer |
| title_full | Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer |
| title_fullStr | Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer |
| title_full_unstemmed | Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer |
| title_short | Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer |
| title_sort | impact of fgfr4 gene polymorphism on the progression of colorectal cancer |
| topic | colorectal cancer fibroblast growth factor receptor 4 single-nucleotide polymorphism metastasis |
| url | https://www.mdpi.com/2075-4418/11/6/978 |
| work_keys_str_mv | AT beihaoshiu impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT minghonghsieh impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT wenchienting impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT mingchihchou impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT lunchingchang impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT chichouhuang impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT shihchisu impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer AT shunfayang impactoffgfr4genepolymorphismontheprogressionofcolorectalcancer |