Vitamin D and Cancer - Research Paper Example

Role of Vitamin D in the Prevention of Cancers: Contents Role of Vitamin D in the Prevention of Cancers 1.0.Introduction: 3 1.Background: 3 1.1.1.Vitamin D and the Colon Cancer: 5 1.1.2.Vitamin D and Breast Cancer: 6 1.2.Approach: 7 2.0.Methods: 8 2.1.Collection of Literature: 8 3.0.Results: 9 3.1.Studies regarding CRC: 10 3.2.Studies about Breast Cancer: 11 3.3.Studies regarding Prostate Cancer: 12 3.4.Studies regarding Pancreatic Cancer: 12 4.0.Discussion: 13 5.0.Conclusion: 14 Figure 1: chemical structure of vitamin D [20] 5 1.0. Introduction: 1.1. Background: Vitamin D is an essential constituent of the diet and it is mandatory for the formation, growth and repair of the bones and it also plays an important role in the absorption of calcium as well as the defense system of the body; it is mainly obtained through the exposure of the body to the ultraviolet radiations of the sun and in minor quantities it can also be derived from some foods and selected diet. There are some studies which showed that increase intake of foods and dietary supplements containing high vitamin D content is associated with decrease incidence of different malignancies for instance colorectal carcinoma, the fact whether vitamin D decreases the incidence of other cancers for example breast, pancreatic or prostate cancer is still unclear. [1] Calcitriol, the hormonally active form of this vitamin have been tested and proven in many of the animal models that it has got growth inhibitory as well as favorable effects on the differentiation of the tumor cells resulting in the slowing down of the tumor cells. So there are several trials which have used vitamin D as an anticancer agent and the main mechanisms of action of this vitamin include inhibition of cell proliferation, decreases inflammation in tumor cells, stimulate the process of apoptosis (the programmed cell death) and it also causes inhibition of the tumor angiogenesis (development of the blood vessels which provide nutrition to the tumor cells), oppose the invasion by the tumor cells and also inhibit metastasis (spread of tumor from one site to the other). [2] The 1st observation which supported this belief that vitamin D prevents cancer came in the mid of the 20th century from the fact that people which were living in the areas with increase sun exposures suffered from a skin cancer usually Squamous Cell Carcinoma (S.C.C) which is not a fatal one usually due to its less likelihood to metastasize but these people showed decrease incidence of serious internal malignancies like breast, prostate or colorectal cancers which supported the fact that vitamin D has a protective effect by decreasing the incidence of malignancies. The role of the vitamin D remains unclear until in the late 1980s when two epidemiologists named Garland brothers stated that adequate sunlight decreased the incidence of Colon Cancer. They also observed that women who were exposed to adequate sunlight have fifty percent less mortality from breast cancer then the women who has relatively less sun exposure and afterwards another researcher named Gary Schwartz observed the same to be true for the prostate cancer and they all were of the view that vitamin D is the main agent behind this observation. The Garlands also showed that low levels of vitamin D also relates with the development of colorectal cancers which also explained their earlier observation in which they showed that people who developed S.C.C were at decreased risk of developing cancers like prostatic carcinoma or colorectal carcinoma and it is due to the increase blood level of Calcitriol in these patients owing to increase exposure to sunlight. Figure 1: chemical structure of vitamin D [20] 1.1.1. Vitamin D and the Colon Cancer: The colon cancer is one of the deadliest and the prevalent form of solid malignancy. In 1980’s Garland Brothers showed that colon cancer has got a decreased incidence in people living in the sunny areas and this was possibly due to increase concentration of Calcitriol in their blood. In 1985, scientists discovered in a study which include more than 2000 men that the incidence of colon cancer was more than double in the patients who were deficient in vitamin D consumption and as a matter of fact most of the Vitamin D comes from the sunlight so minor amounts of vitamin D in the diet can have a protective effect in preventing this lethal malignancy. In 1989, these two researchers showed a direct correlation between the colon cancer and the blood Calcitriol levels and the persons who have their Calcitriol level ranging from 33-41ng/ml were at five times less risk of developing colon cancer. [3] Vitamin D whether as a dietary constituent or as a supplement has a protective role in the colon cancer and in 1999 it was shown by a group of researchers that the cancer cells themselves also secrete Calcitriol which causes the cells to differentiate thus decreasing their malignant potential and they also found that the concentration of Calcitriol was quite high in less aggressive colon carcinomas as compared to advanced metastatic colon cancer in which the Calcitriol concentration was quite low which showed that it may be considered as a natural defense mechanism of the body to prevent from colon cancer. [4] 1.1.2. Vitamin D and Breast Cancer: It has been a long time since the discussion about the role of vitamin D in breast cancer is taking place till a large French study published their results and they included about 67,721 post menopausal women in their studies and they came to conclusion the dietary vitamin D decreases the incidence of breast cancer (CA) and if it is combined with adequate sun exposure then the risk can further be reduced. They observed in the study that the women who are living in the sunny parts of the country have less incidence of breast CA than those living in the less sunny areas. They also concluded that women who are taking less amount of dietary vitamin D but residing in areas with adequate sun exposure had about 32% less chances of developing breast CA then those living at a higher altitudes and the group of women who has sufficient dietary intake of vitamin D along with adequate sun exposure are at least risk of developing this malignancy comparatively. [5] 1.2. Approach: As already mentioned that vitamin d has a protective role in different malignancies specifically colon, prostate and breast cancer. So in order to testify these observations one may plan to conduct a study in which multiple groups of population may be taken representing a sample which is predisposed to develop a certain type of cancer for example in one group, post menopausal women can be taken to assess the development of breast cancer, 2nd group may comprise of men above 70years of age for prostate cancer and a 3rd group for the colon cancer, then in all of the above groups, two sub groups are formed; one with cancer and the other without cancer and then the serum Calcitriol levels are performed in both groups and then the statistical tools are applied on the results to state whether these results are significant or not. 2.0. Methods: 2.1. Collection of Literature: A prospective study was carried out on 15 cases of recurrent prostate cancer and they were given 2000IU of vitamin D per day and they reached to a conclusion that in 9 of these patients who were having treatment refractory prostate cancer, the tumor marker Prostate Specific Antigen (PSA) either declined or remained stable for a period of as long as 21 months. So this can give us a clue that vitamin D may have a role in the treatment of the prostate cancer. On the other hand there was a large prospective trial which measured the level of vitamin D in the patients of prostate cancer and also in the same age group without the malignancy and they found higher levels of vitamin D in the blood of prostate cancer and there was a finding which was though statistically insignificant that the patients with more aggressive tumors have very high levels of vitamin D in the blood. So this negates any role of vitamin D in the prevention of prostate cancer. [6] Chemoprophylaxis is much discussed topic in colorectal carcinoma (CRC) and other gastrointestinal cancers but no specific agent has yet been isolated for this. Aspirin is the best studied chemo preventive agent for CRC but other agents like vitamin D, folic acid and calcium are also studied but they still awaits confirmation and strong evidence. There are studies which showed that using combination of these agents rather than using single agent confers an advantage in chemoprevention for example aspirin is more effective in protecting from CRC if used along with calcium or vitamin D than when it is used alone. [7] 2.1.1. Collection of Literature: 1. Pubmed.gov 2. New England Journal of Medicine (NEJM) 3. Clinical Cancer Prevention - Page 103 Hans-Jorg Senn, Florian Otto – 2011 4. Cancer Nursing: Principles and Practice; Connie Henke Yarbro, Debra Wujcik, Barbara Holmes Gobel – 2010 5. Early Detection and Prevention of Colorectal Cancer-2009 6. Pharmacology for Women's Health; Tekoa L King, Mary C. Brucker – 2009 7. Fundamentals of Cancer Prevention; David S. Alberts, Lisa M. Hess – 2008 8. Trends in cancer prevention research; Frank H. Columbus – 2007 9. Vitamin D and Cancer; Donald L. Trump, Candace S. Johnson – 2010 10. Clinical nutrition in gastrointestinal disease; Alan Buchman – 2006 11. National Cancer Institute 3.0. Results: In this section, different studies will be considered and commented upon to assess the role of vitamin D in the prevention and the treatment of different type of cancers. A study was carried out on about 1200 healthy post menopausal patients who were given Calcium in a dose of 1400mg to 1500mg and vitamin D was given in a dose of 25 micrograms and the other group was given placebo and both of these groups were given this treatment or the placebo for a period of 4 years. The results demonstrated that women who acquired calcium and vitamin D supplementation had a 60% overall low incidence of development of malignancy. But the drawback of this study was that there was no group who was given vitamin D alone and the main motive of the study was to calculate the incidence of fracture not the incidence of malignancy. [8] 3.1. Studies regarding CRC: In a study called the American Cancer Society’s Cancer Prevention Study (CPS) which was the 2nd study of its kind and they observed the diet patterns, medical history and the lifestyle of about 120,000 men and women and they came to a conclusion that the men who had high level of vitamin d intake both through diet and vitamin d supplementation has a slightly low incidence of CRC then the men who had a lower intake of vitamin D but this association was not found in the female group. When the data was collected from about 10 cohort studies including the study mentioned above, it showed a slightly lower incidence of CRC in population with high vitamin D intake as compared to one with low intake of Calcitriol but this difference was statistically insignificant. [9] A trial named Women Health Initiative randomized trial, took healthy women of postmenopausal age and these women were given calcium (1000mg) and vitamin D (400IU) supplementation and another group was given placebo for about 7 years but they reached to a conclusion that the supplementation did not cause any reduction in the incidence of CRC. But some of the researchers negated these results and raised the query that these results could be due to the low levels of vitamin D given to the patients or the duration of the patient follow-up may be inadequate. [10] A study named the Third National Health and Nutrition Examination Survey showed a positive and statistically significant relationship between high levels of Calcitriol and the incidence of deaths from CRC and according to this study, persons with high blood levels of vitamin D (?80nmol/L) had a 72% lower incidence of deaths from CRC than those having low blood levels of vitamin D in the blood (?50nmol/L). [11] 3.2. Studies about Breast Cancer: There are many studies which showed inverse relationship between the incidence of breast cancer and the vitamin D intake but there are studies which showed no association between the incidence and the intake of Calcitriol and there are studies which showed vitamin d to have a positive relationship with the causation of breast cancer. A meta-analysis 0f six studies was performed and it showed no association between the vitamin D intake and breast cancer incidence but in these studies most women were taking low amounts of vitamin D and when this analysis was performed on the women with highest Calcitriol intake (? 400IU/day), then it showed that the breast cancer incidence was lower in this group than the group with the lowest intake of vitamin D (? 50IU/day). [12] When a cohort of post menopausal women were examined who were a part of National Cancer Institute (NCI) Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, during the follow up of these women, 1,005 of these women develop breast cancer and when the vitamin D levels of these women were compared with the same number of women within the group who did not develop breast cancer, there proved to be no association between the risk of breast cancer and the vitamin D levels. [13] 3.3. Studies regarding Prostate Cancer: In one study, blood was drawn from the patient and they were diagnosed 1 to 8 years after drawing of their samples for Calcitriol. The results showed no lowering in the incidence of prostate cancer and the high vitamin D levels in the blood at all rather there were some cases that have high vitamin D levels in the blood and were having more aggressive disease than those having low levels of vitamin D in the blood. [14] 3.4. Studies regarding Pancreatic Cancer: In a study, about 120.000 men and women were taken from the Health Professionals Follow-Up study and the Nurses’ Health Study and this study showed there was a progressively low risk of development of pancreatic cancer in people who have highest intake of vitamin D as compared to those who have the lowest intake, the participants of the survey were followed for a period of about 16 years and total of 365 cases of pancreatic cancers were identified. [15] A study based on the participants of PLCO Screening Trial showed no association between the level of Calcitriol and the risk of pancreatic cancer and in this study they compared the blood’s vitamin D level of 184 patients who developed pancreatic cancer in about 12 years of follow-up and these were compared with 368 cancer free participants. [16] 4.0. Discussion: Now if we discuss the results then we can come to following observations in the light of the above mentioned studies; In case of CRC, increase vitamin D level can be a protective factor in preventing this lethal form of cancer so this can be a form of dietary modification along with diet with less cholesterol and it can be used as a dietary prophylactic measure to decrease the incidence of CRC in high risk population for this cancer. Regarding breast cancers, there are no sufficient studies available to support the protective effect of vitamin D and most of the studies showed no relation between the blood levels and the incidence of breast cancer but there are some studies which showed that highest intake of vitamin D can be a protective factor so high intake of vitamin D can be advised in post menopausal women as it may reduce the chances of malignancy as well as it decreases the chances of fracture due to decrease Bone Mineral density (BMD). The role of vitamin D in the prevention or lowering the risk of development of pancreatic and prostatic cancer is still unclear as on one side there are studies which showed it to be effective in lowering the risk of developing these malignancies, whereas on the other side there are trials showing no relation between the two and even there are studies which showed vitamin D to increase the risk of malignancy or to increase the aggressiveness of the tumor specifically prostatic carcinoma. 5.0. Conclusion: Vitamin D which is an essential part of the diet and the richest source of vitamin D is of course the Sunlight. It may be of valuable importance by protecting us from some of the very deadly form of malignancies like CRC, Breast CA, Pancreatic CA and Prostatic CA. But we should be keeping in mind that excessive exposure to sunlight can be a causative agent of skin cancers especially Squamous Cell Carcinoma (S.C.C). Further research and studies are required to ascertain the role of vitamin D in the cancer prevention and to check whether it has if any role in the treatment of cancers and it is only possible when extensive research is carried out on the possible mechanisms and the chemical pathways involved in the causation of cancers and the role of vitamin D in modification of these pathways. References: Books: 1. Michael F. Holick. Vitamin D: molecular biology, physiology, and clinical applications. 1999. 2. Jorg Reichrath, Michael Friedrich, Wolfgang Tilgen. Vitamin D analogs in cancer prevention and therapy; 2003 3. Ann M. Coulston, Carol Boushey. Nutrition in the prevention and treatment of disease. 2008 4. John D. Potter, Noralane M. Lindor. Genetics of Colorectal Cancer; 2008 5. Donald L. Trump, Candace S. Johnson. Vitamin D and Cancer; 2010 6. MD Facs Robert a Wascher. A Cancer Prevention Guide for the Human Race; 2010 7. Waun Ki Hong, Robert C. Bast, William Hait. Holland Frei cancer medicine eight: Volume 8; 2010 Journals: 8. Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. American Journal of Clinical Nutrition 2007; 85(6):1586–1591. 9. McCullough ML, Robertson AS, Rodriguez C, et al. Calcium, vitamin D, dairy products, and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States). Cancer Causes Control 2003; 14(1):1–12. 10. [Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine 2006; 354(7):684–696. 11. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. Journal of the National Cancer Institute 2007; 99(21):1594–1602. 12. Gissel T, Rejnmark L, Mosekilde L, Vestergaard P. Intake of vitamin D and risk of breast cancer--a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology 2008; 111(3–5):195–199. 13. Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(4):889–894. 14. Ahn J, Peters U, Albanes D, et al. Serum vitamin D concentration and prostate cancer risk: A nested case-control study. Journal of the National Cancer Institute 2008; 100(11):796–804. 15. Skinner HG, Michaud DS, Giovannucci E, et al. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiology, Biomarkers, and Prevention 2006; 15(9):1688–1695. 16. Stolzenberg-Solomon RZ, Hayes RB, Horst RL, et al. Serum vitamin D and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial. Cancer Research 2009; 69(4):1439–1447. Electronic Material: 17. Cannell MD. Vitamin D in Cancer Prevention and Treatment. 2006. [cited 2006 June 04]; [about 3 p.]. Available from: http://www.vitamindcouncil.org/cancerTreatment.shtml 18. Masterjohn C. Vitamin D is Synthesized from Cholesterol and found in Cholesterol- Rich Foods. 2006. [cited 2006 May 25]; [about 8 p.]. Available from: http://www.cholesterol-and-health.com/Vitamin-D.html 19. S. L. Baker. Breast cancer breakthrough: vitamin D in combination with sun exposure is key to prevention. 2011. [cited 2011 January 18]; [about 2 p.]. Available from http://www.naturalnews.com/031042_breast_cancer_sunshine.html 20. National Cancer Institute Fact Sheet. Vitamin D and Cancer Prevention: Strengths and Limits of the Evidence. 2010. [cited 2010 June 16]; [about 9 p.]. Available from http://www.cancer.gov/cancertopics/factsheet/prevention/vitamin-D#r25 Read More