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International Science and Investigation Journal
ISSN: 2251-8576 2016, 5(5)
Journal homepage: www.isijournal.info
On the Cancer of Wild Animals
Somayeh Zaminpira
*1
, Sorush Niknamian
2
*1
Ph.D. in Cellular and Molecular Biology, University of Cambridge, United Kingdom
2
Ph.D. in Cellular and Molecular Biology, University of Cambridge, United Kingdom
Abstract
Cancer affects all animals containing eukaryotic cells. Less is known about the cancers that
affect wild animals, since they move around and may not be easily observed for a long period of
time. This review about cancers in wild animals may have useful data for the study of human
cancers as well. Certain cancers in dinosaurs show that this metabolic disease is primitive and
may have been around since the beginning of the multicellular organisms.
Keywords
Cancer, Wild Animals, Eukaryotic Cells, Multicellular Organisms
Introduction
Cancer
Cancer is a group of diseases that involve abnormal cell division and growth, with the potential
to invade or spread to other parts of the body which is called metastasis. [28] Not all
169
International Science and Investigation Journal Vol. 5(5)
tumors are cancerous. Benign tumors do not spread to other parts of the body. Possible
symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a
change in bowel movements. Although these symptoms may indicate cancer, they may have
other causes. [30] Over 100 kinds of cancers affect humans and also mammalians. [29]
Tobacco use is the cause of around 22 percent of cancer deaths. Another 10 percent is due
to obesity, poor diets, lack of physical activity and drinking alcohol. [31] Other factors
include certain infections, exposure to ionizing radiation and environmental pollutants and
also certain viruses and parasites. [32] In the developing world, nearly 20% of cancers are
due to infections like hepatitis B, hepatitis C and human papillomavirus (HPV). These
factors act by changing the genes of a cell. Typically many genetic changes are required
before cancer develops. [33] Approximately 5 to 10 percent of cancers are because of
inherited genetic defects from a person's parents. [34]
Materials and Methods
Cancer in Dinosaurs
Cancer is a disease that has been around for millions of years. In a 2003 study, researchers
used fluoroscopy and computed tomography (CT) to screen over 10,000 dinosaur vertebrae
specimens for tumors. They found tumors in approximately 3% of the Cretaceous
hadrosaurs specimens, but did not find tumors in any other dinosaur species. The tumors
included hemangiomas, desmoplastic fibroma, and osteoblastoma. [2]
In a research article conducted in 1999, metastatic cancer was found in only 1 out of 548
Edmontosaurus vertebrae sampled and was absent in all remaining samples. Hemangioma
was present in 20 out of 669 Edmontosaurus vertebrae sampled and was absent in all 286
Corythosaurus vertebrae sampled as well as all 7,475 sauropods, ceratopsians, stegosaurs,
theropoda, ornithomimids, and ankylosaurs vertebrae sampled. [3][4]
The statistically significant higher occurrence of hemangiomas found in hadrosaurs than in
other dinosaur species suggests a genetic or environmental basis behind the pattern of
tumor incidence. An example of an environmental factor could be the carcinogenic tannins,
phenols, and resins found in the leaves consumed by these types of dinosaurs. [4]
Tasmanian devil Facial Tumor
Tasmanian Devils were driven to extinction on the Australian mainland thousands of years
ago, after humans introduced dingoes to the continent. The remainder of the wild
population has since inhabited the Australian island-state of Tasmania. In the mid 1990's
the population reached an estimated 150,000 devils.[5] Nowadays, the animals are plagued
by an infectious cancer known as Tasmanian devil facial tumor disease (DFTD). Since the
emergence of the disease in 1996, the population has declined by more than 60 percent. [6]
This type of cancer is very unusual. The great majority of cancer cases in humans and
animals arise from a series of mutations in a single precursor cell and its daughter cells. The
process occurs over a period of years and does not involve contact with any other
individuals. DFTD develops differently. It's transmitted from animal to animal and the
cancer cells themselves are the infectious agent.
This phenomenon is called allograft transmission. An allograft is the term for the transfer of
cells or tissue from one individual to another. An example in humans is organ
170
International Science and Investigation Journal Vol. 5(5)
transplantation. The movement of cancer cells between animals has been confirmed by
cellular and molecular studies. A normal devil cell contains 14 chromosomes.[7] DFTD
tumor cells contain several very distinctive genetic changes and have only 13
chromosomes. Importantly, the tumors from every animal tested appear identical.[7]
Researchers in Tasmania also found a devil with an unusual chromosomal abnormality in
its non-tumorous tissue that did not appear in its tumor cells.[7] These findings strongly
suggest that the cancer did not arise from the animals' own cells.[9][10]
A cancer similar to DFTD occurs in dogs, and is known as Canine Transmissible Venereal
Tumor (CTVT). The immune system of dogs is capable of overcoming the disease, but
devils do not seem to be able to do so. Low genetic diversity among Tasmanian devils
results in close kinship and reduces their immune responses. In conclusion, transplanted
cancer cells are more likely to survive, grow, and spread. [8][11]
Transmission can occur by biting, feeding on the same material, aggressive mating, and
other social interactions. DFTD tumors mostly form on the face and/or in the oral cavity.
The cancer can also metastasize to other areas of the body. Nearly 100% of infected devils
die within 6 months of the onset of clinical signs.[8] Death results from an inability to feed,
secondary infection, or symptoms associated with metastases.
Cancer in Sharks
George Washington University Medical Center researchers reported over thirty tumors
found in elasmobranchs, a group of animals that includes sharks, rays, and skates. [13]
Cancer in Wild Fish
In August of 2012, an article was published that described the discovery of melanoma
affecting a population of wild fish. Plectropomus leopardus which commonly called coral
trout live along the Great Barrier reef. Because the reef is located directly under the largest
known ozone hole, it is thought that the cancer is due to increased exposure of the fish to
ultraviolet (UV) radiation. Ozone normally absorbs the damaging UV rays, but ozone
depletion allows the rays to reach the surface of the earth and the fish. No other causes of
the cancer were identified in this study. UV light is the single greatest risk factor for the
development of melanoma in humans. [23]
Cancer in Naked Mole Rats
Naked mole rats live up to thirty years which is a long life in this species. [24] Although
cancer incidence increases with age, this disease was not observed in this species. By
studying naked mole rats, researchers hoped to discover the keys to cancer resistance.
Ironically, then, cases of cancer have been reported in naked mole rats. [25][26] These case
reports indicate that naked mole rats are not resistant to cancer. One reason for this reported
to be , hyaluronic acid, which was found to be much larger in naked mole rats than in other
mammals. [27]
Conclusion
Almost all animals containing eukaryotic cells can get cancer. There has been some reports
of cancer in Cretaceous hadrosaurs specimens, and this means cancer has been affecting
dinosaurs as well. Tasmanian Devil Facial Tumor is an unusual cancer which is contagious
171
International Science and Investigation Journal Vol. 5(5)
and it's transmitted from animal to animal, and the cancer cells themselves are the infectious
agent. There have been some reports of cancer in sharks and wild fish which shoes this disease
can affect submarine animals too. The most eye catching cancer in wild animals is the type in
naked mole rats which due to the high concentration of hyaluronic acid in their tissues and cell
membranes, which can be of an important issue in human cancer treatment as well.
References
[1] Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2017).
Campbell Biology (11th ed.). Pearson.
[2] Rothschild BM, Tanke DH, Helbling M 2nd, Martin LD. Epidemiologic study of
tumors in dinosaurs. Naturwissenschaften. 2003 Nov; 90(11):495-500. Epub 2003 Oct 14.
[PUBMED]
[3] Rothschild BM, Witzke BJ, Hershkovitz I. Metastatic cancer in the Jurassic. Lancet.
1999 Jul 31;354(9176):398. [PUBMED]
[4] Rehemtulla A. Dinosaurs and ancient civilizations: reflections on the treatment of
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[5] Hawkins et al., Emerging disease and population decline of an island endemic, the
Tasmanian devil Sarcophilus harrisii, Conserv. 131 (2006), pp. 307-324.
[6] Department of Primary Industries and Water (2008) Save the Tasmanian devil
[7] A.M. Pearse and K. Swift, Allograph theory: Transmission of the devil facial-tumor
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[8] R. Frankham et al., A Primer of Conservation Genetics, Cambridge University Press
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[9] P.W. Hedrick and S.T. Kalinowski, Inbreeding depression in conservation biology,
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[10] S.J. OBrien and J.F. Evermann, Interactive influence of infectious disease and genetic
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[11] S. Lachish, H. McCallum, and M. Jones, Demography, disease and the devil: life-
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[12] Holt S: Shark cartilage and nutriceutical update. Altern Complement Ther 1: 414-16,
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[13] Harshbarger JC. 1999 (pers. comm.). Registry of Tumors in Lower Animals. Department
of Pathology, George Washington University Medical Center, Washington, D.C.
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International Science and Investigation Journal Vol. 5(5)
[14] D. J. Prieur, J. K. Fenstermacher, A. M. Guarino, J. Natl. Cancer Inst. 56. 1207 (1976);
S. R. Wellings, Natl. Cancer Inst. Monogr. 31, (1969), p. 59/ J. C. Harshbarger, Activities
Report of The Registry of Tumors In Lower Animals, 1965-1973 (Smithsonian Institution,
Washington, D.C., 1974)
[15] M. L. Moss, Am. Zool. 17, 335 (1977)
[16] O'Reilly MS, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor
growth. Cell. 24;88(2): 277-285, 1997. [PUBMED]
[17] Davis PF, He Y, Furneaux RH, et al.: Inhibition of angiogenesis by oral ingestion of
powdered shark cartilage in a rat model. Microvasc Res 54 (2): 178-82, 1997. [PUBMED]
[18] Lee, Anne, and Robert Langer. "Shark Cartilage Contains Inhibitors of Tumor
Angiogenesis." Science 221 (Sep. 16 1983): 1185-187. [PUBMED]
[19] Leitner SP, Rothkopf MM, Haverstick L, et al.: Two phase II studies of oral dry shark
cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to
standard treatment. [Abstract] Proceedings of the American Society of Clinical Oncology
17: A-240, 1998.
[20] Miller DR, Anderson GT, Stark JJ, et al.: Phase I/II trial of the safety and efficacy of
shark cartilage in the treatment of advanced cancer. J Clin Oncol 16 (11): 3649-55, 1998.
[PUBMED]
[21] Lu C, Lee JJ, Komaki R, et al.: A phase III study of AE-941 with induction
chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell
lung cancer (NSCLC) (NCI T99-0046, RTOG 02-70, MDA 99-303). [Abstract] J Clin
Oncol 25 (Suppl 18): A-7527, 391s, 2007.
[22] Escudier B, Choueiri TK, Oudard S, et al.: Prognostic factors of metastatic renal cell
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[23] Sweet M, Kirkham N, Bendall M, Currey L, Bythell J, et al. (2012) Evidence of
Melanoma in Wild Marine Fish Populations. PLoS ONE 7(8): e41989.
[24] Piersigilli A, Meyerholz DK. The "Naked Truth": Naked Mole-Rats Do Get Cancer.
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[25] Delaney MA, Ward JM, Walsh TF, Chinnadurai SK, Kerns K, Kinsel MJ, Treuting
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[26] Taylor KR, Milone NA, Rodriguez CE. Four Cases of Spontaneous Neoplasia in the
Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species. J Gerontol
A Biol Sci Med Sci. 2016 Apr 29. [PUBMED]
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[27] Gary J. Fisher. Cancer resistance, high molecular weight hyaluronic acid, and
longevity. J Cell Commun Signal. 2015 Mar; 9(1): 91-92.
[28] Cancer Fact sheet N°297. World Health Organization. February 2014. Retrieved 10
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[29] Defining Cancer. National Cancer Institute. Retrieved 10 June 2014.
[30] Cancer - Signs and symptoms. NHS Choices. Retrieved 10 June 2014.
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[32] Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Harikumar KB,
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On the cancer of wild animals somayeh zaminpira - sorush niknamian

  • 1. International Science and Investigation Journal ISSN: 2251-8576 2016, 5(5) Journal homepage: www.isijournal.info On the Cancer of Wild Animals Somayeh Zaminpira *1 , Sorush Niknamian 2 *1 Ph.D. in Cellular and Molecular Biology, University of Cambridge, United Kingdom 2 Ph.D. in Cellular and Molecular Biology, University of Cambridge, United Kingdom Abstract Cancer affects all animals containing eukaryotic cells. Less is known about the cancers that affect wild animals, since they move around and may not be easily observed for a long period of time. This review about cancers in wild animals may have useful data for the study of human cancers as well. Certain cancers in dinosaurs show that this metabolic disease is primitive and may have been around since the beginning of the multicellular organisms. Keywords Cancer, Wild Animals, Eukaryotic Cells, Multicellular Organisms Introduction Cancer Cancer is a group of diseases that involve abnormal cell division and growth, with the potential to invade or spread to other parts of the body which is called metastasis. [28] Not all 169
  • 2. International Science and Investigation Journal Vol. 5(5) tumors are cancerous. Benign tumors do not spread to other parts of the body. Possible symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements. Although these symptoms may indicate cancer, they may have other causes. [30] Over 100 kinds of cancers affect humans and also mammalians. [29] Tobacco use is the cause of around 22 percent of cancer deaths. Another 10 percent is due to obesity, poor diets, lack of physical activity and drinking alcohol. [31] Other factors include certain infections, exposure to ionizing radiation and environmental pollutants and also certain viruses and parasites. [32] In the developing world, nearly 20% of cancers are due to infections like hepatitis B, hepatitis C and human papillomavirus (HPV). These factors act by changing the genes of a cell. Typically many genetic changes are required before cancer develops. [33] Approximately 5 to 10 percent of cancers are because of inherited genetic defects from a person's parents. [34] Materials and Methods Cancer in Dinosaurs Cancer is a disease that has been around for millions of years. In a 2003 study, researchers used fluoroscopy and computed tomography (CT) to screen over 10,000 dinosaur vertebrae specimens for tumors. They found tumors in approximately 3% of the Cretaceous hadrosaurs specimens, but did not find tumors in any other dinosaur species. The tumors included hemangiomas, desmoplastic fibroma, and osteoblastoma. [2] In a research article conducted in 1999, metastatic cancer was found in only 1 out of 548 Edmontosaurus vertebrae sampled and was absent in all remaining samples. Hemangioma was present in 20 out of 669 Edmontosaurus vertebrae sampled and was absent in all 286 Corythosaurus vertebrae sampled as well as all 7,475 sauropods, ceratopsians, stegosaurs, theropoda, ornithomimids, and ankylosaurs vertebrae sampled. [3][4] The statistically significant higher occurrence of hemangiomas found in hadrosaurs than in other dinosaur species suggests a genetic or environmental basis behind the pattern of tumor incidence. An example of an environmental factor could be the carcinogenic tannins, phenols, and resins found in the leaves consumed by these types of dinosaurs. [4] Tasmanian devil Facial Tumor Tasmanian Devils were driven to extinction on the Australian mainland thousands of years ago, after humans introduced dingoes to the continent. The remainder of the wild population has since inhabited the Australian island-state of Tasmania. In the mid 1990's the population reached an estimated 150,000 devils.[5] Nowadays, the animals are plagued by an infectious cancer known as Tasmanian devil facial tumor disease (DFTD). Since the emergence of the disease in 1996, the population has declined by more than 60 percent. [6] This type of cancer is very unusual. The great majority of cancer cases in humans and animals arise from a series of mutations in a single precursor cell and its daughter cells. The process occurs over a period of years and does not involve contact with any other individuals. DFTD develops differently. It's transmitted from animal to animal and the cancer cells themselves are the infectious agent. This phenomenon is called allograft transmission. An allograft is the term for the transfer of cells or tissue from one individual to another. An example in humans is organ 170
  • 3. International Science and Investigation Journal Vol. 5(5) transplantation. The movement of cancer cells between animals has been confirmed by cellular and molecular studies. A normal devil cell contains 14 chromosomes.[7] DFTD tumor cells contain several very distinctive genetic changes and have only 13 chromosomes. Importantly, the tumors from every animal tested appear identical.[7] Researchers in Tasmania also found a devil with an unusual chromosomal abnormality in its non-tumorous tissue that did not appear in its tumor cells.[7] These findings strongly suggest that the cancer did not arise from the animals' own cells.[9][10] A cancer similar to DFTD occurs in dogs, and is known as Canine Transmissible Venereal Tumor (CTVT). The immune system of dogs is capable of overcoming the disease, but devils do not seem to be able to do so. Low genetic diversity among Tasmanian devils results in close kinship and reduces their immune responses. In conclusion, transplanted cancer cells are more likely to survive, grow, and spread. [8][11] Transmission can occur by biting, feeding on the same material, aggressive mating, and other social interactions. DFTD tumors mostly form on the face and/or in the oral cavity. The cancer can also metastasize to other areas of the body. Nearly 100% of infected devils die within 6 months of the onset of clinical signs.[8] Death results from an inability to feed, secondary infection, or symptoms associated with metastases. Cancer in Sharks George Washington University Medical Center researchers reported over thirty tumors found in elasmobranchs, a group of animals that includes sharks, rays, and skates. [13] Cancer in Wild Fish In August of 2012, an article was published that described the discovery of melanoma affecting a population of wild fish. Plectropomus leopardus which commonly called coral trout live along the Great Barrier reef. Because the reef is located directly under the largest known ozone hole, it is thought that the cancer is due to increased exposure of the fish to ultraviolet (UV) radiation. Ozone normally absorbs the damaging UV rays, but ozone depletion allows the rays to reach the surface of the earth and the fish. No other causes of the cancer were identified in this study. UV light is the single greatest risk factor for the development of melanoma in humans. [23] Cancer in Naked Mole Rats Naked mole rats live up to thirty years which is a long life in this species. [24] Although cancer incidence increases with age, this disease was not observed in this species. By studying naked mole rats, researchers hoped to discover the keys to cancer resistance. Ironically, then, cases of cancer have been reported in naked mole rats. [25][26] These case reports indicate that naked mole rats are not resistant to cancer. One reason for this reported to be , hyaluronic acid, which was found to be much larger in naked mole rats than in other mammals. [27] Conclusion Almost all animals containing eukaryotic cells can get cancer. There has been some reports of cancer in Cretaceous hadrosaurs specimens, and this means cancer has been affecting dinosaurs as well. Tasmanian Devil Facial Tumor is an unusual cancer which is contagious 171
  • 4. International Science and Investigation Journal Vol. 5(5) and it's transmitted from animal to animal, and the cancer cells themselves are the infectious agent. There have been some reports of cancer in sharks and wild fish which shoes this disease can affect submarine animals too. The most eye catching cancer in wild animals is the type in naked mole rats which due to the high concentration of hyaluronic acid in their tissues and cell membranes, which can be of an important issue in human cancer treatment as well. References [1] Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2017). Campbell Biology (11th ed.). Pearson. [2] Rothschild BM, Tanke DH, Helbling M 2nd, Martin LD. Epidemiologic study of tumors in dinosaurs. Naturwissenschaften. 2003 Nov; 90(11):495-500. Epub 2003 Oct 14. [PUBMED] [3] Rothschild BM, Witzke BJ, Hershkovitz I. Metastatic cancer in the Jurassic. Lancet. 1999 Jul 31;354(9176):398. [PUBMED] [4] Rehemtulla A. Dinosaurs and ancient civilizations: reflections on the treatment of cancer. Neoplasia. 2010 Dec;12(12):957-68. [PUBMED] [5] Hawkins et al., Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii, Conserv. 131 (2006), pp. 307-324. [6] Department of Primary Industries and Water (2008) Save the Tasmanian devil [7] A.M. Pearse and K. Swift, Allograph theory: Transmission of the devil facial-tumor disease, Nature. 439 (2006), pp. 549. [PUBMED] [8] R. Frankham et al., A Primer of Conservation Genetics, Cambridge University Press (2004). [9] P.W. Hedrick and S.T. Kalinowski, Inbreeding depression in conservation biology, Annu. Rev. Ecol. Syst. 31 (2000), pp. 139-162. [10] S.J. OBrien and J.F. Evermann, Interactive influence of infectious disease and genetic diversity in natural populations, Trends Ecol. Eval. 3 (1988), pp. 234-259. [11] S. Lachish, H. McCallum, and M. Jones, Demography, disease and the devil: life- history changes in a disease-affected population of Tasmanian devils (Sarcophilus harrisii), Journal of Animal Ecology. 78 (2009), pp.427-436. [PUBMED] [12] Holt S: Shark cartilage and nutriceutical update. Altern Complement Ther 1: 414-16, 1995. [13] Harshbarger JC. 1999 (pers. comm.). Registry of Tumors in Lower Animals. Department of Pathology, George Washington University Medical Center, Washington, D.C. 172
  • 5. International Science and Investigation Journal Vol. 5(5) [14] D. J. Prieur, J. K. Fenstermacher, A. M. Guarino, J. Natl. Cancer Inst. 56. 1207 (1976); S. R. Wellings, Natl. Cancer Inst. Monogr. 31, (1969), p. 59/ J. C. Harshbarger, Activities Report of The Registry of Tumors In Lower Animals, 1965-1973 (Smithsonian Institution, Washington, D.C., 1974) [15] M. L. Moss, Am. Zool. 17, 335 (1977) [16] O'Reilly MS, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 24;88(2): 277-285, 1997. [PUBMED] [17] Davis PF, He Y, Furneaux RH, et al.: Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res 54 (2): 178-82, 1997. [PUBMED] [18] Lee, Anne, and Robert Langer. "Shark Cartilage Contains Inhibitors of Tumor Angiogenesis." Science 221 (Sep. 16 1983): 1185-187. [PUBMED] [19] Leitner SP, Rothkopf MM, Haverstick L, et al.: Two phase II studies of oral dry shark cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to standard treatment. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-240, 1998. [20] Miller DR, Anderson GT, Stark JJ, et al.: Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 16 (11): 3649-55, 1998. [PUBMED] [21] Lu C, Lee JJ, Komaki R, et al.: A phase III study of AE-941 with induction chemotherapy (IC) and concomitant chemoradiotherapy (CRT) for stage III non- small cell lung cancer (NSCLC) (NCI T99-0046, RTOG 02-70, MDA 99-303). [Abstract] J Clin Oncol 25 (Suppl 18): A-7527, 391s, 2007. [22] Escudier B, Choueiri TK, Oudard S, et al.: Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941. J Urol 178 (5): 1901-5, 2007. [PUBMED] [23] Sweet M, Kirkham N, Bendall M, Currey L, Bythell J, et al. (2012) Evidence of Melanoma in Wild Marine Fish Populations. PLoS ONE 7(8): e41989. [24] Piersigilli A, Meyerholz DK. The "Naked Truth": Naked Mole-Rats Do Get Cancer. Vet Pathol. 2016 May;53(3):519-20. [PUBMED] [25] Delaney MA, Ward JM, Walsh TF, Chinnadurai SK, Kerns K, Kinsel MJ, Treuting PM. Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber). 2016 May;53(3):691-6. [PUBMED] [26] Taylor KR, Milone NA, Rodriguez CE. Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species. J Gerontol A Biol Sci Med Sci. 2016 Apr 29. [PUBMED] 173
  • 6. International Science and Investigation Journal Vol. 5(5) [27] Gary J. Fisher. Cancer resistance, high molecular weight hyaluronic acid, and longevity. J Cell Commun Signal. 2015 Mar; 9(1): 91-92. [28] Cancer Fact sheet N°297. World Health Organization. February 2014. Retrieved 10 June 2014. [29] Defining Cancer. National Cancer Institute. Retrieved 10 June 2014. [30] Cancer - Signs and symptoms. NHS Choices. Retrieved 10 June 2014. [31] Obesity and Cancer Risk. National Cancer Institute. January 3, 2012. Retrieved 4 July 2015. [32] Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB (September 2008). "Cancer is a preventable disease that requires major lifestyle changes". Pharm. Res. 25 (9): 2097– 116. doi:10.1007/s11095-008-9661-9. PMC 2515569. PMID 18626751. [33] World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 1.1. ISBN 9283204298. [34] Heredity and Cancer. American Cancer Society. Retrieved July 22, 2013. 174