High Serum Level of Retinol and α-Tocopherol Affords Protection Against Oral Cancer in a Multiethnic Population

  • Athirajan, Vimmitra (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya) ;
  • Razak, Ishak Abdul (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya) ;
  • Thurairajah, Nalina (Centre of Pre-U Studies, UCSI University) ;
  • Ghani, Wan Maria Nabillah (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya) ;
  • Ching, Helen-Ng Lee (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya) ;
  • Yang, Yi-Hsin (Department of Dental Hygiene, College of Dental Medicine, Kaohsiung Medical University) ;
  • Peng, Karen-Ng Lee (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya) ;
  • Rahman, Zainal Ariff Abdul (Department of Oral-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University Malaya) ;
  • Mustafa, Wan Mahadzir Wan (Oral Health Division, Ministry of Health Malaysia) ;
  • Abraham, Mannil Thomas (Oral Health Division, Ministry of Health Malaysia) ;
  • Kiong, Tay Keng (Oral Health Division, Ministry of Health Malaysia) ;
  • Mun, Yuen Kar (Oral Health Division, Ministry of Health Malaysia) ;
  • Jalil, Norma (Oral Health Division, Ministry of Health Malaysia) ;
  • Zain, Rosnah Binti (Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University Malaya)
  • Published : 2014.10.23


Background: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol, ${\alpha}$-tocopherol and ${\beta}$-carotene with the risk of oral cancer. Materials and Methods: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, ${\alpha}$-tocopherol and ${\beta}$-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively. Results: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and ${\alpha}$-tocopherol among cases ($0.177{\pm}0.081$, $1.649{\pm}1.670{\mu}g/ml$) were significantly lower than in controls ($0.264{\pm}0.137$, $3.225{\pm}2.054{\mu}g/ml$) (p<0.005). Although serum level of ${\beta}$-carotene among cases ($0.106{\pm}0.159{\mu}g/ml$) were lower compared to controls ($0.134{\pm}0.131{\mu}g/ml$), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and ${\alpha}$-tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between ${\beta}$-carotene and oral cancer risk. Conclusions: High serum levels of retinol and ${\alpha}$-tocopherol confer protection against oral cancer risk.


Oral cancer;micronutrients;retinol;${\alpha}$-tocopherol;${\beta}$-carotene;Malaysia


  1. Aruna DS, Prasad KV, Shavi GR, et al (2011). Retrospective study on risk habits among oral cancer patients in Karnataka Cancer Therapy and Research Institute, Hubli, India. Asian Pac J Cancer Prev, 12,1561-6.
  2. Aune D, De Stefani E, Ronco A, et al (2009). Meat consumption and cancer risk: a case-control study in Uruguay. Asian Pac J Cancer Prev, 10, 429-36.
  3. Benetou V, Orfanos P, Lagiou P, et al (2008). Vegetables and fruits in relation to cancer risk: evidence from the Greek EPIC cohort study. Cancer Epidemiol Biomarkers Prev, 17, 387-92.
  4. Greenwald P, Milner JA, Anderson DE, McDonald SS (2002). Micronutrients in cancer chemoprevention. Cancer Metastasis Rev, 21, 217-30.
  5. De Stefani E, Ronco A, Mendilaharsu M, Deneo-Pellegrini H (1999). Diet and risk of cancer of the upper aerodigestive tract. Oral Oncol, 35, 22-6.
  6. Gallus S, Bosetti C, Franceschi S, et al (2003). Laryngeal cancer in women: tobacco, alcohol, nutritional, and hormonal factors. Cancer Epidemiol Biomarkers Prev, 12, 514-7.
  7. Ghani WM, Doss JG, Jamaluddin M, Kamaruzaman D, Zain RB (2013). Oral cancer awareness and its determinants among a selected Malaysian population. Asian Pac J Cancer Prev, 14, 1957-63.
  8. Gupta V, Kumar P, Kumar P, et al (2012). Oral cancer as a leading annoyance of the South Asian territory: An epidemiologic and clinical review. Clin Cancer Invest J, 1, 196-200.
  9. Helen-Ng LC, Razak IA, Ghani WM, et al (2012). Dietary pattern and oral cancer risk: a factor analysis study. Community Dent Oral Epidemiol, 40, 560-6.
  10. Huang MH, Schocken M, Block G, et al (2002). Variation in nutrient intakes by ethnicity: results from the Study of Women's Health Across the Nation (SWAN). Menopause, 9, 309-19.
  11. Hung HC, Joshipura KJ, Jiang R, et al (2004). Fruit and vegetable intake and risk of major chronic disease. J Nat Cancer Inst, 96, 1577-84.
  12. Jenab M, Riboli E, Ferrari P, et al (2006). Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition. Br J Cancer, 95, 406-15.
  13. Kant AK, Graubard BI (2007). Ethnicity is an independent correlate of biomarkers of micronutrient intake and status in American adults. J Nutr, 137, 2456-63
  14. Lane PM, Gilhuly T, Whitehead P, et al (2006). Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt, 2, 024006.
  15. Klarod K, Hongsprabhas P, Khampitak T, et al (2011). Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients. Nutrition, 27, 1156-60.
  16. Krishnamurthy A, Ramshankar V (2013). Early stage oral tongue cancer among non-tobacco users-an increasing trend observed in a South Indian patient population presenting at a single centre. Asian Pac J Cancer Prev, 14, 5061-5.
  17. Krishna Rao SV, Mejia G, Roberts-Thomson K, Logan R (2013). Epidemiology of oral cancer in Asia in the past decade-an update (2000-2012). Asian Pac J Cancer Prev, 14, 5567-77.
  18. Lawal AO, Kolude B, Adeyemi BF, Lawoyin JO, Akang EE (2012). Serum antioxidant vitamins and the risk of oral cancer in patients seen at a tertiary institution in Nigeria. Niger J Clin Pract, 15, 30-3.
  19. Levi F, Pasche C, La Vecchia C, et al (1998). Food groups and risk of oral and pharyngeal cancer. Int J Cancer, 77, 705-9.<705::AID-IJC8>3.0.CO;2-Z
  20. Lim GCC, Rampai S, Yahaya H (2008). Cancer Incidence in Peninsular Malaysia (2003-2005). The Third Report of the National Cancer Registry of Malaysia (eds). National Cancer Registry, Ministry of Health Malaysia 2008.
  21. Loyha K, Vatanasapt P, Promthet S, Parkin DM (2012). Risk factors for oral cancer in northeast Thailand. Asian Pac J Cancer Prev, 13, 5087-90
  22. Marchioni DL, Fisberg RM, do Rosario M, Latorre DO, Wunsch V (2002). Diet and cancer of oral cavity and pharynx: a case-control study in Sao Paulo, Brazil. IARC Sci Publ, 156, 559-61.
  23. Neville BW, Day TA (2002). Oral cancer and precancerous lesions. CA Cancer J Clin, 52,195-215.
  24. Mukherjee B, Ghosh MK, Hossain CM (2011). Anticancer potential of vitamin A and beta-carotene: mechanistic approach. NSHM J Pharm and Healthcare Management, 2, 1-12.
  25. Nagao T, Ikeda N, Warnakulasuriya S, et al (2000). Serum antioxidant micronutrients and the risk of oral leukoplakia among Japanese. Oral Oncol, 36, 466-70.
  26. Negri E, Franceschi S, Bosetti C, et al (2000). Selected micronutrients and oral and pharyngeal cancer. Int J Cancer, 86, 122-7.<122::AID-IJC19>3.0.CO;2-2
  27. Nomura AM, Stemmermann GN, Lee J, et al (1997). Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev, 6, 487-91.
  28. Pan A, Sun Q, Bernstein AM, et al (2012). Red meat consumption and mortality: Results from 2 prospective cohort studies. Arch Intern Med, 172, 555-63.
  29. Pavia M, Pileggi C, Nobile C, Angelillo IF (2006). Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr, 83, 1126-34.
  30. Persson C, Sasazuki S, Inoue M, et al (2008). Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case-control study. Carcinogenesis, 29, 1042-8.
  31. Petridou E, Zavras AI, Lefatzis D, et al (2002). The role of diet and specific micronutrients in the etiology of oral carcinoma. Cancer, 94, 2981-8.
  32. Poljsak B. (2011). Strategies for reducing or preventing the generation of oxidative stress. Oxidative Medicine and Cellular Longevity, Article ID: 194586.
  33. Shim E, Yeum KJ, Tang G, et al (2012). Retinoids, carotenoids and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients. Nutr Cancer, 64, 956-63.
  34. Priebe SL, Aleksejuniene J, Dharamsi S, Zed C (2008). Oral cancer and cultural factors in Asia. Can J Dent Hygiene, 42, 159-68.
  35. Ross AC, Harrison EH (2007). Vitamin A: nutritional aspects of retinoids and carotenoids. In: Zempleni J, Rucker RB, McCormick DB, and Suttie JW (Eds.) Handbook of Vitamins, 4th Edition, USA: CRC PressTaylor & Francis Group.
  36. Semeraro A, Altieri I, Patriarca M, Menditto A (2009). Evaluation of uncertainty of measurement from method validation data: An application to the simultaneous determination of retinol and ${\alpha}$-tocopherol in human by HPLC. J Chromatogr B, 877, 1209-15.
  37. Siluk D, Oliveira RV, Maria E, et al (2007). A validated liquid chromatography method for the simultaneous determination of vitamins A and E in human plasma. J Pharm Biomed Anal, 44, 1001-7.
  38. Talamini R, Bosetti C, La Vecchia C, et al (2002). Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study. Cancer Causes Control, 13, 957-64.
  39. Tavani A, Malerba S, Pelucchi C, et al (2012). Dietary folates and cancer risk in a network of case-control studies. Ann Oncol, 23, 2737-42.
  40. Thibeault D, Su H, MacNamara E, et al (2009). Isocratic rapid liquid chromatographic method for simultaneous determination of carotenoids, retinol, and tocopherols in human serum. J Chromatogr B Analyt Technol Biomed Life Sci, 877, 1077-83.
  41. Wang C, Baumgartner RN, Yang D, et al (2009). No evidence of association between breast cancer risk and dietary carotenoids, retinols, vitamin C and tocopherols in Southwestern Hispanic and non-Hispanic white women. Breast Cancer Res Treat, 114, 137-45.
  42. Zain RB, Rahman ZAA, Fukano H, et al (1999a). Oral habits, serum micronutrients and oral mucosal lesions among indigenous people of Sarawak. Oral Oncol MacMillan India, 6, 185-8.
  43. Wardlaw GM, Smith AM (2011). Contemporary nutrition, Eighth Edition. USA: McGraw Hill Companies. Inc.
  44. Warnakulasuriya S (2009). Global epidemiology of oral and oropharyngeal cancer. Oral Oncol, 45, 309-6.
  45. Zain RB (2001). Cultural and dietary risk factors of oral cancer and precancer-a brief overview. Oral Oncol, 37, 205-10.
  46. Zain RB, Shanmuhasuntharam P, Fukano H, et al (1999b). Serum micronutrient level in selected Malaysian Indian populationpreliminary findings. J Dent Research, 78, 1172
  47. Zeegers MP, Goldbohm RA, van den Brandt PA (2001). Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study. Br J Cancer, 85, 977-83.
  48. Zheng W, Blot WJ, Diamond EL, et al (1993). Serum micronutrients and the subsequent risk of oral and pharyngeal cancer. Cancer Res, 53,795-8.
  49. Zou CP, Youssef EM, Zou CC, et al (2001). Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RAR beta and on retinoid resistance in human squamous carcinoma cells. Oncogene, 20, 6820-7.

Cited by

  1. Exploratory Study to Evaluate Changes in Serum Lipid Levels as Early Diagnostic and/or Prognostic Indicators for Oral Submucous Fibrosis and Cancer among Gutkha Consumers in India vol.16, pp.15, 2015,
  2. Malnutrition and Oral Disease in the Elderly––Is There Any Bidirectional Relationship? vol.4, pp.2, 2017,
  3. Alcohol Drinking Obliterates the Inverse Association Between Serum Retinol and Risk of Head and Neck Cancer vol.94, pp.26, 2015,