CYP26B1 is a novel candidate gene for betel quid-related oral squamous cell carcinoma

Chen, Ping-Ho; Lee, Ka–Wo; Chen, Chung-Ho; Shieh, Tien-Yu; Ho, P Shing; Wang, Shu-Jung; Lee, Chien-Hung; Yang, Sheau-Fang; Chen, Mu‐Kuan; Chiang, Shang-Lun; Ko, Ying‐Chin

doi:10.1016/j.oraloncology.2011.04.024

Cited by 22 publications

(32 citation statements)

References 28 publications

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“…A CYP26A1 variant reportedly has a significantly reduced activity compared with wild-type (29), but single nucleotide polymorphisms (SNPs) in the CYP26A1 gene have not been linked to disease. The rs707718 polymorphism in CYP26B1 has been associated with oral squamous cell carcinoma in a subgroup of patients (30), but the mechanism behind the link is unclear. It has been unknown if genetic polymorphisms in CYP26B1 influence enzyme efficiency.…”

Section: Introductionmentioning

confidence: 99%

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

Krivospitskaya

Elmabsout

Sundman

et al. 2012

Mol Med

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All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

Krivospitskaya

Elmabsout

Sundman

et al. 2012

Mol Med

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“…Although BQ ingredients vary among regions worldwide, the AN is the primary component. Our previous study indicated that variants of full-length CYP26B1 may be associated with the occurrence of BQ-related OSCC [7]. In addition, a previous study indicated that RA metabolizing enzymes CYP26B1 are overexpressed significantly in colorectal cancer and that CYP26B1 is significantly associated with the prognosis of colorectal cancer patients [31].…”

Section: Discussionmentioning

confidence: 99%

“…Details on the method used for western blotting are provided in our previous report [7]. Mouse antihuman CYP26B1 monoclonal antibodies (Abnova, Taipei City, Taiwan) were used as the first antibody at a 1 : 1000 dilution, and a horseradish-peroxidase conjugated antimouse antibody (Cell signaling Co.) was used as the second antibody at a 1 : 1000 dilution.…”

Section: Methodsmentioning

confidence: 99%

“…BQ is a psychostimulant and an addictive carcinogenic substance [2, 3]. The areca nut (AN) is the primary ingredient in various BQ products, and the International Agency for Research on Cancer (IARC) has classified the AN as a group I human carcinogen based on findings indicating that it is associated with an elevated risk for oral potentially malignant disorders (OPMDs, such as leukoplakia, oral submucous fibrosis, erythroplakia, and lichen planus) and cancers of the oral cavity, pharynx, and esophagus [3–7]. …”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies indicating that arecoline induces both in vivo and in vitro suggest that the CYP26B1 variants play a vital role in BQ-related oral and pharyngeal cancers [7, 28]. We investigated whether susceptible CYP26B1 genes and, particularly, their splicing variants are associated with oral and pharyngeal cancer.…”

Section: Introductionmentioning

confidence: 99%

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Expression of a Splice Variant of CYP26B1 in Betel Quid-Related Oral Cancer

Chen

Lee

Hsu

et al. 2014

The Scientific World Journal

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Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.

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A variant in CYP26B1 associated with esophageal squamous cell carcinoma risk by affecting retinoic acid metabolism

Niu

Shi

Yue

et al. 2023

Molecular Carcinogenesis

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All‐trans retinoic acid (ATRA) is the natural and synthetic analogue of vitamin A, playing an essential tumor suppressive role in multiple cancers including the esophageal squamous cell carcinoma (ESCC). Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) exerts a critical regulator of ATRA levels through specific inactivation of ATRA to hydroxylated forms. Our previous exome‐wide analyses revealed a rare missense variant in CYP26B1 significantly associated with ESCC risk in the Chinese population. However, it is still unclear whether there are common variants in CYP26B1 affect the susceptibility of ESCC and the tumor promotion role of CYP26B1 in vivo. In this research, we conducted a two‐stage case‐control study comprised of 5057 ESCC cases and 5397 controls, followed by a series of biochemical experiments to explore the function of CYP26B1 and its common variants in the tumorigenesis of ESCC. Intriguingly, we identified a missense variant rs2241057[A>G] in the fourth exon of CYP26B1 significantly associated with the ESCC risk (combined odds ratio = 1.28; 95% confidence interval = 1.15–1.42; p = 2.96 × 10−6). Through further functional analysis, we demonstrated that ESCC cells with the overexpression of rs2241057[G] had a significant lower level of retinoic acid, compared with the overexpression of rs2241057[A] or the control vector. In addition, the CYP26B1 overexpression and knock‐out ESCC cells affected cell proliferation rate both in vitro and in vivo. These results highlighted the carcinogenicity of CYP26B1 related to the ATRA metabolism in ESCC risk.

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CYP26B1 is a novel candidate gene for betel quid-related oral squamous cell carcinoma

Cited by 22 publications

References 28 publications

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis

Expression of a Splice Variant of CYP26B1 in Betel Quid-Related Oral Cancer

A variant in CYP26B1 associated with esophageal squamous cell carcinoma risk by affecting retinoic acid metabolism

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