1Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Sultanate of Oman.2Department of Nutrition, High Institute of Public Health, Alexandria University, Egypt. 3Department of Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman. 4Department of Epidemiology, School of Public Health, Boston University, USA
*Corresponding Author: Dr. Mostafa Waly. Email: email@example.com
Driven by the boom of wealth brought by oil discovery and production, the high rate of urbanization and a steady increase in the per capita income, during the past years, has improved the socio-economic status of the people in the Arabian Gulf Cooperation Countries (GCC). This radical economic change has been accompanied by drastic changes in their lifestyle and food consumption patterns. During the past years, the regular consumption of traditional foods is being replaced with more Western-style and ready-made foods. In addition to adopting a sedentary life style in daily life and other related activities. According to National Health Survies in the GCC countries, high daily caloric intake, refined carbohydrates and protein were associated with increased risk of non-communicable diseases including colorectal cancer (CRC). The rate of CRC among GCC countries is in the rise; however, there is dearth of research exploring it. In particular, there is lack of research about role of folate on occurrence of CRC despite the recent flourishing scientific research papers from other parts of the world.
Cancer is considered a leading cause of death worldwide, accounting for 7.6 million of all deaths from a total of 58 million deaths reported in year 2005 and the (WHO) estimates that there will be 20 million new cases and 12 million deaths from cancer alone by the year 2020 (1). Furthermore the WHO reported that in Western countries, the rate of colorectal cancer (CRC) has increased dramatically as compared to other types of cancers, and this increase was attributed to westernization in food choices and dietary pattern as well as adopting a sedentary lifestyle (1). The Arabian Gulf Cooperation Council (GCC) countries include the following six countries: Oman, United Arab Emirates, Saudi Arabia, Qatar, Bahrain, and Kuwait (2).
The GCC countries have witnessed rapid change in many aspects of life during the last 5 decades because of the boom of wealth that coincided with the discovery and production of oil (3). This boom has transformed these countries from being traditional nomadic societies to become affluent metropolitan cities in a very short time. This rapid change resulted in an immense effect of the life style of people, and their social life. This is quite notable with the proliferation of western pattern of lifestyle especially in nutrition and physical inactivity (4). The rapid socio-economic transition might also have affected the pattern of cancer in these countries. It has been quite notable that incidence rates of cancer have increased in other countries that went through rapid industrialization because of the lifestyle risk factors including diet, physical activity, obesity which appears to play an important role in the etiology of the disease (5).
Recent reports indicate that migrant populations moved from countries of low CRC and incidence to the West adopted the high CRC incidence trend of the new country (6-8). These observations suggest that changes in diet and lifestyle might contribute to the incidence of CRC, and therefore research had focused in identifying the dietary pattern and lifestyle characteristics that might contribute to primary prevention of CRC. The international experts from the recent World Cancer Research Fund Report, 2008, concluded that CRC is a major public health problem and modernization in food choices, sedentary life style and increased life expectancy are the major factors that might synergize with genetics for the epidemic of CRC worldwide (9).
It is timely to conduct research studies to elucidate the underpinning risk factors of cancer, in general, and colorectal cancer, in particular, in the GCC countries. In the GCC countries, there are few published reports about the dietary pattern and lifestyle characteristics of CRC among adults. Generally, it has been noted that the rate of CRC among GCC countries is considered relatively low compared to most of western countries. Nonetheless, the pattern is in the rise (10). In Oman, CRC ranked third after breast cancer and stomach cancer (11). Similar pattern has been observed in Qatar and Saudi Arabia where it ranked second after breast cancer, and in both countries it constituted for 9% of the newly diagnosed cases (12). In a comparative review among Arab countries, it has been noted that the rates of CRC among Bahrain and Kuwait were higher than other Arab countries (10). Sporadic studies about CRC in the GCC countries do exist. They are mainly cross-sectional epidemiological studies that describe the pattern of annual change of cancer rates in general, and among them CRC is noted (13). Fewer studies are case-control studies that explored underlying risk factors (14). To our best knowledge, studies that explore the relation between folate and CRC in the GCC countries have not been yet reported. The following sections provide an overview of the molecular mechanisms of the role of folate in occurrence of CRC.
There are several established dietary risk factors for CRC, largely related to folate and/or vitamin B12 deficiency (15, 16), diets from animal sources that are low in fibre and high in fat (17-19). Meanwhile, allium vegetables, fruits, pulses and foods containing selenium protect against CRC cancer (20-22). Non dietary risk factors for CRC include, decreased physical activity (23), obesity ,a body mass index (BMI) of greater than or equal to 30 kg/m2 (24, 25), genetic susceptibility (26, 27), alcohol (28, 29), smoking (30), and exposure to environmental carcinogens that may lead to proliferation and malignant transformation of colorectal cells (31, 32).
Folate and vitamin B12 deficiency induce carcinogenesis in susceptible persons, via mechanisms that involve cell signaling, cell division and DNA methylation. The protective effect of folate and vitamin B12 is attributed to its one carbon folate metabolism, including the methionine cycle that is regulated by ubiquitous enzyme, methionine synthase (MS). The mechanism involves the necessity of 5-methyltetrahydrofolate (5-CH3-THF) as a methyl donor and vitamin B12 as a cofactor for MS that regulates the homocysteine (HCY) remethylation to methionine and synthesis of S-adenosylmethionine (SAM), the universal biochemical methyl donor for all biological methylation reactions, including DNA methylation (33).Numerous studies have indicated that under conditions of low dietary intake of folate and vitamin B12, the methyl supply is low and consequently the MS activity is low concomitant with low SAM levels and DNA hypomethylation, a leading cause of mutagenesis and abnormal expression of oncogenes, which have been implicated in different types of carcinogenesis (34-36).
As illustrated in Figure 1, folate-dependent methionine cycle modulates HCY availability for the transsulfuration into cysteine. Homocysteine (HCY) is converted to methionine by methionine synthase enzyme (MS), which utilizes vitamin B12 as a cofactor and acquires a methyl group from, 5-methyltetrahydrofolate (5-CH3-THF) which is then converted to tetrahydrofolate (THF). Methionine is further converted to S-Adenosylmethionine (SAM) through the activity of methionine adenosyltransferase. SAM is the major methyl donor for all methyltransferases enzymes, which add methyl groups to various acceptor molecules such as DNA, RNA, phospholipids and proteins. SAM is then converted to S-Adenosylhomocysteine (SAH), which is then reversibly converted to HCY in a reaction catalyzed by SAH-hydrolase. HCY is either re-methylated back to methionine or transsulfurated to glutathione (GSH), the major cellular antioxidant.
Figure 1: Simplified schematic diagram of the folate-dependent HCY methylation and transsulfuration pathway
Folate-dependent transulfuration pathway is the precursor for de-novo synthesis of reduced glutathione (GSH), a tripeptide of glutamic acid, cysteine, and glycine. GSH is the major intracellular antioxidant and it undergoes oxidation to the disulfide form (GSSG), oxidized form, when scavenging reactive oxygen species (ROS) that are highly unstable molecules. In healthy cells and tissues, more than 90% of the total glutathione pool is in the reduced form (GSH), and less than 10% exists in the disulfide form (GSSG), and a reduced GSH/GSSG ratio is an indication of oxidative stress (37, 38). Oxidative stress is a condition under which the intracellular antioxidant (GSH), antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase), and dietary antioxidants (vitamin C, selenium, β carotene and vitamin E) are not counterbalancing the ROS, and subsequently induce cellular damage which is involved in the pathogenesis of cancer. Vegetables and fruits are good sources of antioxidants that provide a protective effect against the ROS-mediated DNA and lipids cell membrane structures damage in proliferated cells (39, 40).
In conclusion various Western studies have revealed that CRC carcinogenesis is modifiable in accordance to certain dietary factors with potential anticancer properties. Such studies are needed to be conducted in the Arabian Gulf region, in order to address the intake of bioactive food components in the diet consumed by vulnerable groups at risk for CRC. Addressing the physical activity is an asset to develop a multidisciplinary approach for the primary prevention of CRC among high risk population. In the Arabian Gulf region, primary prevention of CRC is feasible through intervention programs such as; establishing a biochemical profile for early diagnosis of CRC and adopting long-term behavior modifications in food choices, dietary pattern and physical activity.
- World Health Organization, Geneva, 2006 (Fact Sheet No. 297).
- Fasano U, Iqbal Z. GCC Countries: from oil dependence to diversification. International Moentary Fund, Publication services. Washington, DC. Second edition, 2003
- AlAdawi S. Emergence of diseases of affluence in Oman: Where do they feature in the health research agenda? Sultan Qaboos Univ Med J. 2006;6: 3–9.
- Waly MI, Ali A, Essa MM, Al-Shuaibi Y, Al-Farsi YM. The global burden of type 2 diabetes: a review. International Journal of Biological and Medical Research 2010; 1(4): 326-329.
- Giovannucci E. Modifiable risk factors for colon cancer. Gastroenterology Clinics of North America 2002; 31(4):925-943.
- Harding S, Rosato M, Teyhan A. Trends in cancer mortality among migrants in England and wales, 1979-2003. Eur J Cancer 2009; 45(12): 2168-2179.
- Ronellenfitsch U, Kyobutungi C, Ott JJ, Paltiel A, Razum O, Schwarzbach M, Winkler V, Becher H. Stomach cancer mortality in two large cohorts of migrants from the former Soviet Union to Israel and Germany: are there implications for prevention? Eur J Gastroenterol Hepatol 2009; 21(4): 409-416.
- Sung JJ, Lau JY, Goh KL, Leung WK. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncology 2005; 6: 871–876.
- World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR). Food, Nutrition and the Prevention of Cancer; a Global Perspective. Washington, DC: American Institute for Cancer Research. 2008.
- Salim EI, Moore MA, Al-Kayed S. Cancer epidemiology in the Arab region-past, present and future. Asian Pac J Cancer Prev 2009; 10:27-44.
- Al-Hamdan N, Ravichandran, Al-Sayyad K, Al-Lawati J, Khazal Z, Al-Khateeb F, Abdulwahab A, Al-Asfour A. Incidence of cancer in Gulf Cooperation Council countries, 1998–2001. Cancer Epidemiol Biomarkers Prev 2008; 17(9):22-27.
- Bener A, Ayub H, Kakil R. Patterns of cancer incidence among the population of qatar: A worldwide comparative study. Asian Pac J Cancer Prev 2007; 9:19-24.
- Bener A, Moore MA, Ali R, El Ayoubi HR. Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar. Asian Pac J Cancer Prev 2010; 11:963-968.
- Bener A, El Ayoubi HR, Chouchane L. The impact of consanguinity on cancer in a highly endogamous population. Asian Pac J Cancer Prev 2009; 10:35-40.
- Choi S, Mason JB. Folate and carcinogenesis: An integrated scheme. Journal of Nutrition 2000; 130: 129-132.
- Waly MI, Arafa MA, Jriesat SB, Sallam SA. Folate and Vitamin B12 deficiency is associated with colorectal cancer in Jordan. International Journal of Nutrition, Pharmacology and Neurodegenerative Diseases 2012; 2: 57-60.
- Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat and fiber intake to the risk of colon cancer in a prospective study among women. New England Journal of Medicine 1990; 13: 1664–1672.
- Slattery ML, Berry TD, Potter J, Caan B. Diet diversity, diet composition and risk of colon cancer (United States). Cancer Causes and Control 1997; 8:872–882.
- Arafa MA, Waly MI, Jriesat SB, Al-Khafajei AM, Sallam SA. Dietary and lifestyle characteristics of colorectal cancer in Jordan: a case-control study. Asian Pacific Journal for Cancer Prevention 2011; 12:2007-2012.
- Yang WG, Chen CB, Wang ZX, Liu YP, Wen XY, Zhang SF, Sun TW. A case-control study on the relationship between salt intake and salty taste and risk of gastric cancer. World J Gastroenterol. 2011; 17(15):2049-2053.
- Zhou Y, Zhuang W, Hu W, Liu GJ, Wu TX, Wu XT. Consumption of large amounts of Allium vegetables reduces risk for gastric cancer in a meta-analysis. Gastroenterology. 2011; 141(1):80-89.
- Soerjomataram I, Oomen D, Lemmens V, Oenema A, Benetou V, Trichopoulou A, Coebergh JW, Barendregt J, de Vries E. Increased consumption of fruit and vegetables and future cancer incidence in selected European countries. Eur J Cancer. 2010; 46(14):2563-2580.
- Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. Journal of Nutrition 2002 (132): 3456S–3464S.
- Calle EE, Rodriguez C, Walker-Thrumind K , Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003; 348 (17):1625-1638.
- Frezza EE, Wachtel MS, Chiriva-Internati M. Influence of obesity on the risk of developing colon cancer. Gut 2006; 55: 285–291.
- Jass JR What is new in hereditary colorectal cancer? Archives of Pathology and Laboratory Medicine. 2005;129: 1380–1384.
- Heavy PM, McKenna D , Rowland IR Colorectal cancer and the relationship between genes and the environment. Nutrition and Cancer 2004; 48:124–141.
- Shimizu N, Nagata C, Shimizu H, Kametani M, Takeyama N, Ohnuma T , Matsushita S. Height, weight, and alcohol consumption in relation to the risk of colorectal cancer in Japan: a prospective study. Br J Cancer 2003; 7:1038-1043.
- Wu AH, Paganin-Hill A, Ross RK, Henderson BE. Alcohol, physical activity, and other risk factors for colorectal cancer: a prospective study. Br J Cancer 1987; 55: 687–694.
- Ulrich CM, Bigler J, Whitton JA, Bostick R, Fosdick L, Potter JD. Epoxide hydrolase Tyr113His polymorphism is associated with elevated risk of colorectal polyps in the presence of smoking and high meat intake. Cancer Epidemiolo Biomarkers Prev 2001; 10: 875–882.
- IARC Working groups on the Evaluation of Carcinogenic Risks to Humans. Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxin. Vol. 56. IARC monograph on the evaluation of carcinogenic risks to humans.1993.
- Irigaray P, Newby JA, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S , Belpomme D. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine and Pharmacotherapy 2007; 61: 640-658.
- Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. 10th edition. Edited by Lippincott Williams & Wilkins. USA; 2006; pp: 550-552.
- Sibani S, Melnyk S, Pogribny IP, Wang W, Hiou-Tim F, Deng L, Trasler J, James SJ, Rozen R. Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in min mice. Carcinogenesis, 2002; 23:61-65.
- Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 1985; 228:187-190.
- Baylin SB, Makos M, Wu JJ, Yen RW, de Bustros A, Vertino P, Nelkin BD. Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 1991; 3:382-390.
- Struzyńska L, Chalimoniuk M, Sulkowski G. The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity. Toxicology 2005; 212:185-194.
- Bain JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Rev 1997; 25:335-358.
- La Vecchia C, Altieri A, Tavani A. Vegetables, fruit, antioxidants and cancer: a review of Italian studies. Eur J Nutr 2001; 40: 261-267.
- Greenberg ER, Baron JA, Tosteson TD. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. New England Journal of Medicine 1994; 21:141-147.