Skip to main content
SpringerLink
Log in

Betel Nut and Susceptibility to Cancer

  • Chapter
  • First Online:
Environmental Factors, Genes, and the Development of Human Cancers

Abstract

Betel nut is a widely masticated natural product, which is consumed by over 600 million people across the globe. The ancient habit of betel nut chewing, either as dry or raw/wet nut, in association with betel leaf and a host of region specific additives, including chewing tobacco, is believed to be an important etiological factor for human cancer. Alkaloids and their betel nut specific nitrosamine derivatives produced upon metabolic activation interact with DNA and other cellular targets to produce highly variable mutagenic, genotoxic, cytostatic, immunostatic and teratogenic effects. At molecular level the betel nut or its constituents strongly influence gene expression patterns, especially that of tumor suppressor genes. Structural damage to nucleus and mitochondria, etc. are also induced. The review dwells upon these aspects of betel nut induced carcinogenesis to show that genetic susceptibility to cancer through generations progressively increased due to exposure to betel nut.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Balachandran, B., Sharan, R. N. 1995. Induction of mutations by different extracts of betel nut and radiation: Their implication in carcinogenesis. In Radiation Research 1895–1995, eds. U. Hagen, H. Jung, and C. Streffer, pp 165, vol. 1, Würzburg: Universitätsdruckerei H. Stürtz AG.

    Google Scholar 

  • Bartsch, H., Hietanen, E. 1996. The role of individual susceptibility in cancer burden related to environmental exposure. Environ Health Perspect 104:569–577.

    PubMed  CAS  Google Scholar 

  • Bhattacharjee, C., Sharan, R. N. 2008. Aqueous extract of betel nut (AEBN) induced adducts on pMTa4 DNA acquires stability in the presence of Na+ and K+ ions. Mol. Med. Rep. 1:435–441.

    CAS  Google Scholar 

  • Boucher, B. J., Mannan, N. 2002. Metabolic effects of the consumption of Areca catechu. Addict. Biol. 7:103–110.

    Article  PubMed  CAS  Google Scholar 

  • Chang, M. C., Ho, Y. S., Lee, P. H., Chan, C. P., Lee, J. J., Hahn, L. J., Wang, Y. J., Jeng, J. H. 2001d. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22:1527–1535.

    Article  PubMed  CAS  Google Scholar 

  • Chang, Y. C., Hu, C. C., Lii, C. K., Tai, K. W., Yang, S. H., Chou, M. Y. 2001b. Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin. Oral Investig. 5:51–56.

    Article  PubMed  CAS  Google Scholar 

  • Chang, Y. C., Hu, C. C., Tseng, T. H., Tai, K. W., Lii, C. K., Chou, M. Y. 2001a. Synergistic effects of nicotine on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts. J. Oral Pathol. Med. 30:458–464.

    Article  PubMed  CAS  Google Scholar 

  • Chang, B., Liao, M., Kuo, M. Y., Chen, C. 2001c. Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos. Birth Defects Res. 70:28–36.

    Article  Google Scholar 

  • Chang, M. C., Wu, H. L., Lee, J. J., Lee, P. H., Chang, H. H., Hahn, L. J., Lin, B. R., Chen, Y. J., Jeng, J. H. 2004. The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation. J Biol Chem 279:50676–50683.

    Article  PubMed  CAS  Google Scholar 

  • Chen, C. L., Chi, C. W., Chang, K. W., Liu, T. Y. 1999. Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history. Carcinogenesis 20:2331–2334.

    Article  PubMed  CAS  Google Scholar 

  • Chiang, C., Chang, M., Lee, J., Chang, J. Y., Lee, P., Hahn, L., Jeng, J. 2004. Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch. Oral Oncol. 40:720–727.

    Article  PubMed  Google Scholar 

  • Chiang, S., Jiang, S., Wang, Y., Chiang, H., Chen, P., Tu, H., Ho, K., Tsai, Y., Chang, I., Ko, Y. 2007. Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci 100:66–74.

    Article  PubMed  CAS  Google Scholar 

  • Chiba, I., Muthumala, M., Yamazaki, Y., Zaman, A. U., Iizuka, T., Amemiya, A., Shibata, T., Kashiwazaki, H., Sugiura, C., Fukuda, H. 1998. Characteristics of mutations in the p53 gene of oral squamous-cell carcinomas associated with betel-quid chewing in Sri Lanka. Int J Cancer 77:839–842.

    Article  PubMed  CAS  Google Scholar 

  • Chiu, C. J., Chang, C. P., Hahn, L. J., Hsieh, L. L., Chen, C. J. 2002. Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol. Biomarkers. Prev. 11:646–653.

    PubMed  CAS  Google Scholar 

  • Chiu, C. J., Chiang, C. P., Chang, M. L., Chen, H. M., Hahn, L. J., Hsieh, L. L., Kuo, Y. S., Chen, C. J. 2001. Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer. J. Dent. Res. 80:2055–2059.

    Article  PubMed  CAS  Google Scholar 

  • Choudhury, Y., Sharan, R. N. 2009. Altered p53 response and enhanced transgenerational transmission of carcinogenic risk upon exposure of mice to betel nut. Environ. Toxicol. Pharmacol. 27:127–138.

    Google Scholar 

  • Choudhury, Y., Sharan, R. N. 2010. Altered BRCA1 and BRCA2 response and mutation of BRCA1 gene m mice exposed chronically and transgenerationally to aqueous extract of betel nut. Environ. Toxicol. Pharmacol. (in communication)

    Google Scholar 

  • Chung, K. T., Wong, T. Y., Wei, C. I., Huang, Y. W., Lin, Y. 1998. Tannins and human health: a review. Crit. Rev. Food Sci. Nutr. 38:421–464.

    Article  PubMed  CAS  Google Scholar 

  • Cressman, V. L., Backlund, D. C., Avrutskaya, A., Leadon, S. A., Godfrey, V., Koller, B. H. 1999. Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1-deficient mice. Mol Cell Biol 19:7061–7075.

    PubMed  CAS  Google Scholar 

  • Deb, S., Chatterjee, A. 1998. Influence of buthionine sulfoximine and reduced glutathione on arecoline-induced chromosomal damage and sister chromatid exchange in mouse bone marrow cells in vivo. Mutagenesis 13:243–248.

    Article  PubMed  CAS  Google Scholar 

  • Deng, J. F., Ger, J., Tsai, W. J., Kao, W. F., Yang, C. C. 2001. Acute toxicities of betel nut: rare but probably overlooked events. J Toxicol Clin Toxicol 39:355–360.

    Article  PubMed  CAS  Google Scholar 

  • Desai, S. S., Ghaisas, S. D., Jakhi, S. D., Bhide, S. V. 1996. Cytogenetic damage in exfoliated oral mucosal cells and circulating lymphocytes of patients suffering from precancerous oral lesions. Cancer Lett. 109:9–14.

    Article  PubMed  CAS  Google Scholar 

  • Goan, Y. G., Chang, H. C., Hsu, H. K., Chou, Y. P., Cheng, J. T. 2005. Risk of p53 gene mutation in esophageal squamous cell carcinoma and habit of betel quid chewing in Taiwanese. Cancer Sci. 96:758–765.

    Article  PubMed  CAS  Google Scholar 

  • Harris, C. C., Hollstein, M. 1993. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329:1318–1327.

    Article  PubMed  CAS  Google Scholar 

  • Hollstein, M., Sidransky, D., Vogelstein, B., Harris, C. C. 1991. P53 mutation in human cancer. Science 253:49–53.

    Article  PubMed  CAS  Google Scholar 

  • Hsieh, L. L., Wang, P. F., Chen, I. H., Liao, C. T., Wang, H. M., Chen, M. C., Chang, J. T., Cheng, A. J. 2001. Characterisics of mutations of the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese. Carcinogenesis 22:1497–1503.

    Article  PubMed  CAS  Google Scholar 

  • Hsu, H. J., Chang, K. L., Yang, Y. H., Shieh, T. Y. 2001. The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. Kaohsiung J Med Sci 17:175–182.

    PubMed  CAS  Google Scholar 

  • Hung, S., Cheng, Y., Peng, J., Chang, L., Liu, T., Chen, Y. 2005. Inhibitory effects of areca nut extracts on phagocytosis of Actinobacillus actinomycetemcomitans ATCC 33384 by neutrophils. J. Periodontol. 76:373–379.

    Article  PubMed  Google Scholar 

  • IARC. 1985. International Agency for Research on Cancer (IARC) – Tobacco habits other than smoking: Betel quid and Areca-nut chewing and some related nitrosamines. IARC Monogr Eval Carcinog Risks Hum 37:263, Lyon: IARC.

    Google Scholar 

  • IARC. 2004. International Agency for Research on Cancer (IARC) – Summaries & Evaluations: Betel-quid and areca-nut chewing. IARC Monogr Eval Carcinog Risk Chem Hum 85:39, Lyon: IARC.

    Google Scholar 

  • Jeng, J. H., Chang, M. C., Hahn, L. J. 2001. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol. 37:477–492.

    Article  PubMed  CAS  Google Scholar 

  • Jeng, J. H., Kuo, M. L., Hahn, L. J., Kuo, M. Y. 1994. Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J. Dental Res. 73:1043–1049.

    CAS  Google Scholar 

  • Jeng, J. H., Lan, W. H., Hahn, L. J., Hsieh, C. C., Kuo, M. Y. 1996. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J. Oral Pathol. Med. 25:371–375.

    Article  PubMed  CAS  Google Scholar 

  • Jeng, J. H., Tsai, C. L., Hahn, L. J., Yang, P. J., Kuo, Y. S., Kuo, M. Y. 1999. Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities. Food Chem Toxicol 37:751–756.

    Article  PubMed  CAS  Google Scholar 

  • Jeng, J. H., Wang, Y. J., Chiang, B. L., Lee, P. H., Chan, C. P., Ho, Y. S., Wang, T. M., Lee, J. J., Hahn, L. J., Chang, M. C. 2003. Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24:1301–1315.

    Article  PubMed  CAS  Google Scholar 

  • Kannan, K., Munirajan, A. K., Krishnamurthy, J. 1999. Low incidence of p53 mutation in betel quid and tobacco chewing-associated oral squamous carcinoma from India. Int J Oncol 15:1133–1136.

    PubMed  CAS  Google Scholar 

  • Kao, S. Y., Wu, H. C., Lin, S. C., Yap, S. K., Chang, C. S., Wong, Y. K., Chi, L. Y., Liu, T. Y. 2002. Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use. J. Oral Pathol. Med. 31:505–511.

    Article  PubMed  CAS  Google Scholar 

  • Kato, K., Hara, A., Kuno, T., Kitaori, N., Huilan, Z., Mori, H., Toida, M., Shibata, T. 2005. Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity. J. Cancer Res. Clin. Oncol. 131:340–346.

    Article  PubMed  CAS  Google Scholar 

  • Kietthubthew, S., Sriplung, H., Au, W. W. 2001. Genetic and environmental interactions on oral cancer in Southern Thailand. Environ Mol Mutagen 37:111–116.

    Article  PubMed  CAS  Google Scholar 

  • Kinzler, K. W., Vogelstein, B. 1997. Gatekeeprs and caretakers. Nature 386:761–763.

    Article  PubMed  CAS  Google Scholar 

  • Kumpawat, K., Deb, S., Ray, S., Chatterjee, A. 2003. Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Mutat Res 538:1–12.

    Article  PubMed  CAS  Google Scholar 

  • Kuttan, N. A. A., Rosin, M. P., Ambika, K., Priddy, R. W., Bhakthan, N. M. G., Zhang, L. 1995. High prevalence of expression of p53 oncoprotein in oral carcinomas from India associated with betel and tobacco chewing. Eur J Cancer 31:169–173.

    Google Scholar 

  • Lai, K., Lee, T. 2006. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutat. Res. Fundam. Mol. Mech. Mutag. 599:66–75.

    Article  CAS  Google Scholar 

  • Lane, D. P. 1992. Cancer: p53 guardian of the genome. Nature 358:15–16.

    Article  PubMed  CAS  Google Scholar 

  • Lee, P., Chang, M., Chang, W., Wang, T., Wang, Y., Hahn, L., Ho, Y., Lin, C., Jeng, J. 2006. Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis. Toxicology 220:81–89.

    Article  PubMed  CAS  Google Scholar 

  • Lee, H., Yin, P., Yu, T., Chang, Y., Hsu, W., Kao, S., Chi, C., Liu, T., Wei, Y. 2001. Accumulation of mitochondrial DNA deletions in human oral tissues — effects of betel quid chewing and oral cancer. Mutat. Res. Genetic Toxicol. Environ. Mutagen. 493:67–74.

    Article  CAS  Google Scholar 

  • Levine, A. J. 1997. P53, the cellular gatekeeper for growth and division. Cell 88:323–331.

    Article  PubMed  CAS  Google Scholar 

  • Lin, Y., Jen, Y., Wang, B., Lee, J., Kang, B. 2005. Epidemiology of oral cavity cancer in Taiwan with emphasis on the role of betel nut chewing. ORL J. Otorhinolaryngol. Relat. Spec. 67:230–236.

    Article  PubMed  Google Scholar 

  • Lin, S. C., Liu, C. J., Yeh, W. I., Lui, M. T., Chang, K. W., Chang, C. S. 2006. Functional polymorphism in NFKB1 promoter is related to risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers. Cancer Lett. 243:47–54.

    Article  PubMed  CAS  Google Scholar 

  • Liu, T., Chen, C., Chi, C. 1996. Oxidative damage to DNA induced by areca nut extract. Mutat. Res. Genetic Toxicol. 367:5–31.

    Google Scholar 

  • Liu, T. Y., Chi, C. W. 1999. Areca nut extracts stimulate DNA strand breaks by generation of nitric oxide. Toxicol Lett 95:112.

    Article  Google Scholar 

  • Liu, T. Y., Chung, Y. T., Wang, P. F., Chi, C. W., Hsieh, L. L. 2004. Safrole-DNA adducts in human peripheral blood—an association with areca quid chewing and CYP2E1 polymorphisms. Mutat. Res. Genetic Toxicol. Environ. Mutagen. 559:59–66.

    Article  CAS  Google Scholar 

  • Liu, S. Y., Lin, M. H., Yang, S. C., Huang, G. C., Chang, L., Chang, S., Yen, C. Y., Chiang, W. F., Kuo, Y. Y., Chen, L. L., Lee, C. H., Liu, Y. C. 2005a. Increased expression of matrix metalloproteinase-2 in oral cells after short-term stimulation and long-term usage of areca quid. J. Formos. Med. Assoc. 104:390–397.

    PubMed  CAS  Google Scholar 

  • Liu, S. Y., Lin, M. H., Yang, S. C., Huang, G. C., Chang, L., Chang, S., Yen, C. Y., Chiang, W. F., Lee, C. H., Kuo, Y. Y., Liu, Y. C. 2005b. Areca quid chewing enhances the expression of salivary matrix metalloproteinase-9. J. Formos. Med. Assoc. 104:113–119.

    PubMed  CAS  Google Scholar 

  • Lu, S., Chang, K., Liu, C., Tseng, Y., Lu, H., Lee, S., Lin, S. 2006. Ripe areca nut extract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte. Carcinogenesis 27:1273–1284.

    Article  PubMed  CAS  Google Scholar 

  • Nadeau, G., Boufaied, N., Moisan, A., Lemieux, K. M., Cayanan, C., Monteiro, A. N. A., Gaudreau, L. 2000. BRCA1 can stimulate gene transcription by a unique mechanism. EMBO Rep. 3:260–265.

    Article  Google Scholar 

  • Nair, U., Bartsch, H., Nair, J. 2004. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 19:251–262.

    Article  PubMed  CAS  Google Scholar 

  • Nair, U., Floyd, R. A., Nair, J., Bussachini, V., Friesen, M., Bartsch, H. 1987. Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact 63:157–169.

    Article  PubMed  CAS  Google Scholar 

  • Nair, U. J., Nair, J., Mathew, B., Bartsch, H. 1999. Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/ tobacco chewers. Carcinogenesis 20:743–748.

    Article  PubMed  CAS  Google Scholar 

  • Nair, J., Ohshima, H., Friesen, M., Croisy, A., Bhide, S. V., Bartsch, H. 1985. Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis 6:295–303.

    Article  PubMed  CAS  Google Scholar 

  • Norton, S. A. 1998. Betel: consumption and consequences. J Am Acad Dermatol 38:81–88.

    Article  PubMed  CAS  Google Scholar 

  • Panigrahi, G. B., Rao, A. R. 1989. Study of the genotoxicity of the total aqueous extract of betel nut and its tannin. Carcinogenesis 7:37–39.

    Article  Google Scholar 

  • Pariat, T., Balachandran, B., Sharan, R. N. 1999. Effects of carcinogen exposure on poly-ADP-ribosylation of HMG Proteins and on chromatin organization. In Recent Aspects of Cellular and Applied Radiobiology, eds. F. H. A. Schneeweiss and R. N. Sharan, pp 158–161, vol. 30, International co-operation bilateral seminars series, Juelich: Forschungszentrum Juelich GmbH.

    Google Scholar 

  • Pariat, T., Sharan, R. N. 1998a. Betel nut and diethylnitrosamine induced conformational changes in the liver HMG proteins in vivo. In Trends in Radiation and Cancer Biology, ed. R. N. Sharan, pp 162–165, vol. 29, International co-operation bilateral seminars series, Juelich: Forschungszentrum Juelich GmbH.

    Google Scholar 

  • Pariat, T., Sharan, R. N. 1998b. Qualitative change in mice liver HMG proteins after low dose chronic administration of aqueous extract of betel nut and diethynitrosamine. Hepatol Res 12:177–185.

    Article  Google Scholar 

  • Pariat, T., Sharan, R. N. 2002. Role of mouse spleen cell HMG proteins and its poly-ADP-ribosylation in betel nut induced carcinogenesis. Indian J Biochem Biophys 39:130–132.

    PubMed  CAS  Google Scholar 

  • Patel, B. P., Shah, S. V., Shukla, S. N., Shah, P. M., Patel, P. S. 2007. Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. Head Neck 29:564–572.

    Article  PubMed  Google Scholar 

  • Paul, K., Moitra, P. K., Mukherjee, I., Maity, C., Ghosal, S. K. 1999. Teratogenicity of arecoline hydrobromide on developing chick embryos: A preliminary report. Bull Environ Contam Toxicol 62:356–362.

    Article  PubMed  CAS  Google Scholar 

  • Polasa, K., Babu, S., Shenolikar, I. S. 1993. Dose-dependent genotoxic effect of pan masala and areca nut in Salmonella typhimurium assay. Food Chem Toxicol 31:439–442.

    Article  PubMed  CAS  Google Scholar 

  • Rajan, J. V., Wang, M., Marquis, S. T., Chodosh, L. A. 1996. Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proc. Natl. Acad. Sci. (USA) 93:13078–13083.

    Article  CAS  Google Scholar 

  • Ralhan, R., Agarwal, S., Nath, N., Mathur, M., Wasylyk, B., Srivastava, A. 2001. Correlation between p53 gene mutations and circulating antibodies in betel- and tobacco-consuming North Indian population. Oral Oncol. 37:243–250.

    Article  PubMed  CAS  Google Scholar 

  • Ramachandran, S., Ramadas, K., Hariharan, R., Rejnish, K. R., Radhakrishna, P. M. 2006. Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer. Oral Oncol. 42:350–362.

    Article  PubMed  CAS  Google Scholar 

  • Ranasinghe, A. W., Warnakulasuriya, K. A. A. S., Johnson, N. W. 1993. Low prevalence of expression of p53 oncoprotein in oral carcinomas from Sri Lanka associated with betel and tobacco chewing. Eur J Cancer 29:147–150.

    Article  Google Scholar 

  • Saikia, J. R., Schneeweiss, F. H. A., Sharan, R. N. 1998. Effects of chronic low-dose arecoline administration on the macromolecular components of bone marrow and spleen cells of mice. Cancer J. 11:94–98.

    CAS  Google Scholar 

  • Saikia, J. R., Schneeweiss, F. H. A., Sharan, R. N. 1999a. Chronic low dose arecoline exposure affects DNA, RNA and protein contents and cellular poly-ADP-ribosylation in mice in vivo. In Recent Aspects of Cellular and Applied Radiobiology, eds. F. H. A. Schneeweiss, and R. N. Sharan, pp 149–152, vol. 30, International co-operation bilateral seminars series, Juelich: Forschungszentrum Juelich GmbH.

    Google Scholar 

  • Saikia, J. R., Schneeweiss, F. H. A., Sharan, R. N. 1999b. Arecoline-induced changes of poly-ADP-ribosylation of cellular proteins and its influence on chromatin organization. Cancer Lett. 139:59–65.

    Article  PubMed  CAS  Google Scholar 

  • Sharan, R. N. 1994. Biochemical investigation of carcinogenic potency of betel nut (Kwai) of north-east India. In, Oral Oncology, pp. 190–193, vol. III, New Delhi: Mac Millan India Ltd.

    Google Scholar 

  • Sharan, R. N. 1996. Association of betel nut with carcinogenesis – A review. Cancer J. 9:13–19.

    CAS  Google Scholar 

  • Sharan, R. N., Wary, K. K. 1992. Study of unscheduled DNA synthesis following exposure of human cells to arecoline and extracts of betel nut in vitro. Mutat Res 278:271–276.

    Article  PubMed  CAS  Google Scholar 

  • Shwe, M., Chiguchi, G., Yamada, S., Nakajima, T., Maung, K. K., Takagi, M., Amagasa, T., Tsuchida, N. 2001. P53 and MDM2 co-expression in tobacco and betel chewing-associated oral squamous cell carcinomas. J. Med. Dent. Sci. 48:113–119.

    PubMed  CAS  Google Scholar 

  • Sinha, A., Rao, A. R. 1985a. Embryotoxicity of betel nuts in mice. Toxicol. 37:315–326.

    Article  CAS  Google Scholar 

  • Sinha, A., Rao, A. R. 1985b. Induction of shape abnormality and unscheduled DNA synthesis by arecoline in the germ cells of mice. Mutat Res 158:189–192.

    Article  PubMed  CAS  Google Scholar 

  • Sinha, A., Rao, A. R. 1985c. Transplacental micronucleus inducing ability of arecoline, a betel nut alkaloid in mice. Mutat Res 158:193–194.

    Article  PubMed  CAS  Google Scholar 

  • Spitz, M. R., Bondy, M. L. 1993. Genetic susceptibility to cancer. Cancer. 72:991–995.

    Article  PubMed  CAS  Google Scholar 

  • Stich, H. F., Anders, F. 1989. The involvement of reactive oxygen species in oral cancers of betel quid/tobacco chewers. Mutat Res 214:47–61.

    Article  PubMed  CAS  Google Scholar 

  • Sundqvist, K., Liu, Y., Nair, J., Bartsch, H., Arvidson, K., Grafström, R. C. 1989. Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res 49:5294–5298.

    PubMed  CAS  Google Scholar 

  • Thomas, S., Brennan, J., Martel, G. 1994. Mutations in the conserved regions of p53 are infrequent in betel-associated oral cancers from Papua New Guinea. Cancer Res 54:3588–3593.

    PubMed  CAS  Google Scholar 

  • Topcu, Z., Chiba, I., Fujieda, M., Shibata, T., Ariyoshi, N., Yamazaki, H., Sevgican, F., Muthumala, M., Kobayahi, H., Kamataki, T. 2002. CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka. Carcinogenesis 23:595–598.

    Article  PubMed  CAS  Google Scholar 

  • Trivedy, C. R., Craig, G., Warnakulasuriya, S. 2002. The oral health consequences of chewing areca nut. Addict. Biol. 7:115–125.

    Article  PubMed  CAS  Google Scholar 

  • Tseng, C. 2006. Betel nut chewing is independently associated with urinary albumin excretion rate in type 2 diabetic patients. Diabetes Care 29:462–463.

    Article  PubMed  Google Scholar 

  • Tu, H. F., Liu, C. J., Chang, C. S., Lui, M. T., Kao, S. Y., Chang, C. P., Liu, T. Y. 2006. The functional (-1171 5A→>6A) polymorphisms of matrix metalloproteinase 3 gene as a risk factor for oral submucous fibrosis among male areca users. J. Oral Pathol. Med. 35:99–103.

    Article  PubMed  CAS  Google Scholar 

  • Tu, H. F., Wu, C. H., Kao, S. Y., Liu, C. J., Liu, T. Y., Lui, M. T. 2007. Functional-1562 C-to-T polymorphism in matrix metalloproteinase-9 (MMP-9) promoter is associated with the risk for oral squamous cell carcinoma in younger male areca users. J. Oral Pathol. Med. 36:409–414.

    Article  PubMed  CAS  Google Scholar 

  • Wang, C. K., Peng, C. H. 1996. The mutagenicities of alkaloids and N-nitrosoguvacoline from betel quid. Mutat Res Environ Mutagen Relat Subj 360:165–171.

    Article  CAS  Google Scholar 

  • Warnakulasuriya, S. 2002. Areca nut use: an independent risk factor for oral cancer. Br. Med. J. 324:799–800.

    Article  Google Scholar 

  • Wary, K. K., Sharan, R. N. 1988. Aqueous extract of betel-nut of North-East India induces DNA strand breaks and enhances rate of cell proliferation in vitro. J. Cancer Res. Clin. Oncol 114:579–582.

    Article  PubMed  CAS  Google Scholar 

  • Wary, K. K., Sharan, R. N. 1991. Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro. Int J Cancer 47:396–400.

    Article  PubMed  CAS  Google Scholar 

  • Wen, X., Zhang, Y., Liu, X., Guo, S., Wang, H. 2006. Immune responses in mice to arecoline mediated by lymphocyte muscarinic acetylcholine receptor. Cell Biol. Int. 30:1048–1053.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

RNS acknowledges contributions of all research associates and scholars whose work has been cited in this review. Grants of UGC, CSIR, DST and ICMR, which supported different aspects of research embodied in this chapter, are also acknowledged. Part of the ongoing research is being carried out under a research scheme partly funded by the UPE-NEHU grant. YC was supported by a fellowship (NET-JRF/SRF) from the UGC and is currently working as a Lecturer, Department of Biotechnology, Assam University, Silchar, 788 011, India.

Author information

Authors and Affiliations

  1. Radiation and Molecular Biology Unit, Department of Biochemistry, North-Eastern Hill University, Shillong, 793 022, India

    Rajesh N. Sharan & Yashmin Choudhury

Authors
  1. Rajesh N. Sharan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yashmin Choudhury
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh N. Sharan .

Editor information

Editors and Affiliations

  1. Robert Stempel School of Public Health, Dept. Environmental & Occupational Healt, Florida International University, SW. 8th Street 11200, Miami, 33199-0001, Florida, USA

    Deodutta Roy

  2. Robert Stempel College of Public Health, Department of Environmental and Occupati, Florida International University, Miami, 33199-0001, Florida, USA

    M. Tevfik Dorak

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+ Business Media, LLC

About this chapter

Cite this chapter

Sharan, R.N., Choudhury, Y. (2010). Betel Nut and Susceptibility to Cancer. In: Roy, D., Dorak, M. (eds) Environmental Factors, Genes, and the Development of Human Cancers. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6752-7_15

Download citation

Publish with us

Policies and ethics

Search

Navigation