Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers

Wang, Tong Hong; Hsia, Shih Min; Shih, Yin Hwa; Shieh, Tzong‐Ming

doi:10.3390/ijms18061210

Cited by 51 publications

(38 citation statements)

References 126 publications

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“…While the acquired genetic factors cannot be controlled in their early steps of mutation accumulation, environmental exposure can significantly affect the pathogenesis and the prognosis of these patients [ 8 , 9 ]. The major environmental components are tobacco smoking, betel quid chewing, alcohol consumption, and poor oral hygiene and infections, alongside other specific dietary habits or specific pollutant exposure [ 6 , 7 , 10 , 11 ]. The totality of risk factors are integrated into the exposome [ 12 ], this being an important step in the evaluation of internal and external exposure, generally related to the co-occurrence of multiple toxic environmental agents [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients

Irimie

Braicu

Cojocneanu

et al. 2018

IJERPH

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Smoking is a well-known behavior that has an important negative impact on human health, and is considered to be a significant factor related to the development and progression of head and neck squamous cell carcinomas (HNSCCs). Use of high-dimensional datasets to discern novel HNSCC driver genes related to smoking represents an important challenge. The Cancer Genome Atlas (TCGA) analysis was performed in three co-existing groups of HNSCC in order to assess whether gene expression landscape is affected by tobacco smoking, having quit, or non-smoking status. We identified a set of differentially expressed genes that discriminate between smokers and non-smokers or based on human papilloma virus (HPV)16 status, or the co-occurrence of these two exposome components in HNSCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways classification shows that most of the genes are specific to cellular metabolism, emphasizing metabolic detoxification pathways, metabolism of chemical carcinogenesis, or drug metabolism. In the case of HPV16-positive patients it has been demonstrated that the altered genes are related to cellular adhesion and inflammation. The correlation between smoking and the survival rate was not statistically significant. This emphasizes the importance of the complex environmental exposure and genetic factors in order to establish prevention assays and personalized care system for HNSCC, with the potential for being extended to other cancer types.

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Section: Introductionmentioning

confidence: 99%

Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients

Irimie

Braicu

Cojocneanu

et al. 2018

IJERPH

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“…In addition, high expression of circ_0000199 was associated with betel quid chewing, tumor size, and lymph node metastasis, suggesting its potential clinical application as an independent factor for predicting survival and disease recurrence of OSCC patients. The epidemiological studies have showed that betel quid chewing is closely related to the occurrence of OSCC 23 . In 2003, the World Health Organization identified betel nut as a primary carcinogen.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Luo

Liu

Guo

et al. 2020

Sci Rep

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Studies have found that circRnA in exosomes is associated with oral squamous cell carcinoma (oScc) progression. In this study, we examined the expression of circ_0000199 in circulating exosomes from patients with oScc and its role in the evaluation of relapse and prognosis. Real-time quantitative reverse transcription-polymerase chain reaction was performed to assess circ_0000199 expression in circulating exosomes from 108 patients with OSCC and 50 healthy people. Gain-and loss-functional experiments were performed to assess the role of circ_0000199 on cell proliferation and apoptosis in OSCC cells. Our results showed that the high level of circ_0000199 in circulating exosomes was significantly associated with betel quid chewing, tumor size, lymphatic metastasis, and TNM stage in patients with OSCC. In addition, the patients with high exosomal circ_0000199 had higher tumor recurrence rate and higher mortality rate than the patients with low exosomal circ_0000199. Overexpression of circ_0000199 promoted, while knockdown of circ_0000199 inhibited OSCC cell growth. Bioinformatics analysis predicted that circ_0000199 interacted with miR-145-5p and miR-29b-3p simultaneously, which were involved in multiple tumor-related signaling pathways. in conclusion, upregulation of circ_0000199 in circulating exosomes from patients with OSCC is positively associated with poor survival outcome. Circulating exosomal circ_0000199 can be used as a biomarker and potential therapeutic target for oScc. Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the world, accounting for 3% of malignant tumors 1. Although the treatment of OSCC has made breakthroughs in the past decades, the 5-year mortality rate is still less than 50% 2. Early diagnosis and early treatment are the keys to improve the survival rate of patients with OSCC. Exosomes have phospholipid bilayer membrane with the markers TSG101 and CD63. The size of exosomes ranges from 30 to 100 nm. These vesicles exist in almost all body fluids of the human body, including blood, serum, saliva, cerebrospinal fluid, and urine 3. Exosomes contain various substances, such as proteins, DNA, microRNA (miRNA), circular RNA (circRNA). These molecules can be transported to regulate the signaling pathways of the recipient cells 4. CircRNAs are covalently formed from the ends of a single RNA molecule, without 5′ and 3′ ribonucleotide end, and circRNAs are expressed abundantly, conserved and stably in cells with temporal and spatial specificity 5. CircRNAs can bind to miRNAs to inhibit their functions. Therefore, circRNA is also called miRNA sponge. With the continuous understanding of circRNA, researchers have found that circRNAs are widely involved in the occurrence and development of physiology and disease as well as tumors 6. As a new type of regulatory endogenous RNA, circRNAs are expected to become a tumor diagnostic marker and therapeutic target due to its characteristics such as stability, conservation, and tissue-specific expression 7. For example, circRNA_...

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“…Cigarette smoking and alcohol consumptions are other risk factors for oral cancer [32]. Those habits also cause alteration of DNA methylation [33,34]. In fact, previous studies demonstrate clear evidence that development of oral cancer follows the same biological pathways irrespective of the source of carcinogenic exposure [35,36].…”

Section: Discussionmentioning

confidence: 99%

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

et al. 2020

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Background: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. Results: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). Conclusions: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.

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Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers

Cited by 51 publications

References 126 publications

Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients

Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

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