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The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

ABSTRACT: Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

SUBMITTER: Chen PH

PROVIDER: S-EPMC4214165 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

Chen Ping-Ho PH Huang Bin B Shieh Tien-Yu TY Wang Yan-Hsiung YH Chen Yuk-Kwan YK Wu Ju-Hui JH Huang Jhen-Hao JH Chen Chun-Chia CC Lee Ka-Wo KW

TheScientificWorldJournal 20141015

Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the suscep ...[more]

PMID: 25389533

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Project description:BackgroundAreca nut (AN), the principal ingredient of betel quid (BQ) has been categorized as a human carcinogen associated with various cancers of upper aerodigestive tract. However, there has been no attempt at summarizing the risk reversal of oral and other cancers after cessation of BQ with or without tobacco (BQ+T/BQ-T).ObjectiveTo analyze the effect of cessation of betel quid without tobacco (BQ-T) and with tobacco (BQ+T) on reversal of the risk of oral, pharyngeal and oesophageal cancers.MethodsA systematic literature search was conducted for publications evaluating risk of these three cancers among current and former users of BQ-T or BQ+T. The overall as well as subgroup meta-relative risks (meta-RR) were estimated using random-effect models.ResultsA total of 14 studies, seven each providing estimates for BQ-T and BQ+T, were identified. For BQ-T and oral cancer, a 28.9% risk reversal was observed among former users (meta-RR 5.61, 95% CI 2.24-14.04) compared to current users (meta-RR 7.89, 95% CI 3.90-15.98). A risk reversal of 48% was noted for pharyngeal cancer - former users (meta-RR 2.50, 95% CI 1.43-4.38), current users (meta-RR 4.81, 95% CI 2.05-11.30). For oesophageal cancer, no appreciable difference in risk was observed between current and former users.For BQ+T and oral cancer the overall meta-RR indicated a higher risk in former than in current users. However, sensitivity analysis including only better-quality studies showed a modestly lower cancer risk in former than in current users. Compared to current users, the risk in former users who quit less than 10 years ago (meta-RR 1.21, 95% CI 0.90-1.63) was increased, but decreased in former users who quit more than 10 years ago (meta-RR 0.72, 95% CI 0.48-1.07).ConclusionOur analysis highlights for the first time the potential of risk reversal for oral and pharyngeal cancers following cessation of BQ-T and for oral cancer in long-term quitters (greater than 10 years) of BQ+T. The suggestive evidence from this systematic review further supports the imperative need of a strong policy to reduce the initiation of BQ use and inclusion of interventions for BQ cessation in cancer control efforts especially in geographic regions where BQ chewing is prevalent.

Project description:ImportanceBetel-quid (BQ) is the fourth most popular psychoactive agent worldwide. An emerging trend across Asia is the addictive consumption of BQ, which is associated with oral cancer and other health consequences.ObjectiveTo investigate the validity and pattern of DSM-5-defined BQ use disorder (BUD) and its association with oral potentially malignant disorder (OPMD) among Asian populations.Design, setting, and participantsIn-person interviews were conducted from January 1, 2009, to February 28, 2010, among a random sample of 8922 noninstitutionalized adults from the Asian Betel-quid Consortium study, an Asian representative survey of 6 BQ-endemic populations. Statistical analysis was performed from January 1, 2015, to December 31, 2016.Main outcomes and measuresParticipants were evaluated for BUD using DSM-5 criteria for substance use disorder and for OPMD using a clinical oral examination. Current users of BQ with 0 to 1 symptoms were classified as having no BUD, those with 2 to 3 symptoms as having mild BUD, those with 4 to 5 symptoms as having moderate BUD, and those with 6 or more symptoms as having severe BUD.ResultsAmong the 8922 participants (4564 women and 4358 men; mean [SD] age, 44.2 [0.2] years), DSM-5 symptoms showed sufficient unidimensionality to act as a valid measure for BUD. The 12-month prevalence of DSM-5-defined BUD in the 6 study populations was 18.0% (mild BUD, 3.2%; moderate BUD, 4.3%; and severe BUD, 10.5%). The 12-month proportion of DSM-5-defined BUD among current users of BQ was 86.0% (mild BUD, 15.5%; moderate BUD, 20.6%; and severe BUD, 50.0%). Sex, age, low educational level, smoking, and drinking were significantly associated with BUD. Among individuals who used BQ, family use, high frequency of use, and amount of BQ used were significantly linked to moderate to severe BUD. Compared with individuals who did not use BQ, those who used BQ and had no BUD showed a 22.0-fold (95% CI, 4.3-112.4) risk of OPMD (P < .001), whereas those with mild BUD showed a 9.6-fold (95% CI, 1.8-56.8) risk (P = .01), those with moderate BUD showed a 35.5-fold (95% CI, 4.3-292.3) risk (P = .001), and those with severe BUD showed a 27.5-fold (95% CI, 1.6-461.4) risk of OPMD (P = .02). Individuals with moderate to severe BUD who used BQ and had the symptom of tolerance had a 153.4-fold (95% CI, 33.4-703.6) higher risk of OPMD than those who did not use BQ, and those with moderate to severe BUD who used BQ and had a larger amount or longer history of BQ use had an 88.9-fold (95% CI, 16.6-476.5) higher risk of OPMD than those who did not use BQ.Conclusions and relevanceThis international study gathered data about BQ users across 6 Asian populations, and it demonstrates that DSM-5 symptoms could fulfill a BUD construct. Most current Asian users of BQ already have BUD, which is correlated with risk of OPMD. Among individuals with moderate to severe BUD who used BQ, tolerance and a larger amount or longer history of BQ use are the key symptoms that correlated with enhanced risk of OPMD. These findings play an important role in providing a new indication of an additional psychiatric management plan for users of BQ who have BUD.

Project description:Betel Quid (BQ) chewing independently contributes to oral, hepatic and esophageal carcinomas. Strong association of breast cancer risk with BQ chewing in Northeast Indian population has been reported where this habit is prodigal. We investigated genomic alterations in breast cancer patients with and without BQ chewing exposure. Twenty six BQ chewers (BQC) and 17 non BQ chewer (NBQC) breast cancer patients from Northeast India were analyzed for genomic alterations and pathway networks using SNP array and IPA. BQC tumors showed significantly (P<0.01) higher total number of alterations, as compared with NBQC tumors, 48 ± 17% versus 32 ± 25 respectively. Incidence of gain in fragile sites in BQC tumors were significantly (P<0.001) higher as compared with NBQC tumors, 34 versus 23% respectively. Two chromosomal regions (7q33 and 21q22.13) were significantly (p<0.05) associated with BQC tumors while two regions (19p13.3-19p12 and 20q11.22) were significantly associated with NBQC tumors. GO terms oxidoreductase and aldo-keto reductase activity in BQC tumors in contrast to G-protein coupled receptor protein signaling pathway and cell surface receptor linked signal transduction in NBQC tumors were enriched in DAVID. One network "Drug Metabolism, Molecular Transport, Nucleic Acid Metabolism" including genes AKR1B1, AKR1B10, ETS2 etc in BQC and two networks "Molecular Transport, Nucleic Acid Metabolism, Small Molecule Biochemistry" and "Cellular Development, Embryonic Development, Organismal Development" including genes RPN2, EMR3, VAV1, NNAT and MUC16 etc were seen in NBQC. Common alterations (>30%) were seen in 27 regions. Three networks were significant in common regions with key roles of PTK2, RPN2, EMR3, VAV1, NNAT, MUC16, MYC and YWHAZ genes. These data show that breast cancer arising by environmental carcinogens exemplifies genetic alterations differing from those observed in the non exposed ones. A number of genetic changes are shared in both tumor groups considered as crucial in breast cancer progression.

Dataset Information

The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

Publications

The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

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