Several parasitic species are well known to have carcinogenic properties, namely; Schistosoma hematobium (squamous cell carcinoma of the bladder) and the liver flukes Opisthorchis and Chlonorchis (cholangiocarcinoma). A large number of parasites are known to colonize the gastrointestinal tract. We sought to review the evidence that implicates these parasites in gastrointestinal neoplasia. Schistosoma japonicum, which is endemic primarily in east Asia, has been shown in multiple studies to convey a mildly increased risk of colorectal adenocarcinoma. The data supporting a causative role for Schistosoma mansoni in colorectal or other neoplastic processes are less convincing, limited primarily to small case-control studies and case series. Reports of possible associations between other gastrointestinal parasites (e.g., E. histolytica and A. lumbricoides) and neoplasia may be found in the literature but are limited to individual cases. We conclude that, other than S. japonicum and to a lesser extent S. mansoni, there is little evidence of an association between gastrointestinal parasites and neoplasia. 1. Introduction A wide variety of parasites are known to cause disease in the human gastrointestinal tract, including some species that are very prevalent over a large geographical area. Human parasites are traditionally divided into two broad groups, protozoa and helminths. The phylum protozoa includes a number of gastrointestinal parasites, with some notable members such as Entamoeba histolytica, Giardia lamblia, Cryptosporidia, and Trypansoma cruzi. The multi cellular helminths are further divided into three groups, cestodes/tapeworms (e.g., Taenia solium and Diphyllobothrium latum), nematodes/round worms (e.g., Ascaris lumbricoides, Strongyloides stercoralis, and Enterobius vermicularis), and trematodes/flukes (e.g., Schistosoma japonicum and Schistosoma mansoni). There has long been scientific interest in exploring the possibility of infectious causes of cancer, including bacterial, viral, and parasitic causes. Mathematical modeling has estimated that approximately 16% of cancers throughout the world may be attributable to infection [1]. The fraction of this that is attributable to parasitic infection is currently unknown. Historically, one of the first proposed links between parasitosis and cancer garnered Dr. J. A. G. Fibiger the Nobel Prize in 1926 for his work demonstrating that mice infected with the nematode Spiroptera later developed stomach cancer. This work was later debunked on at least two levels. It was shown that the risk of “cancer” was only
References
[1]
P. Pisani, D. M. Parkin, N. Mu？oz, and J. Ferlay, “Cancer and infection: estimates of the attributable fraction in 1990,” Cancer Epidemiology Biomarkers & Prevention, vol. 6, no. 6, pp. 387–400, 1997.
[2]
I. M. Modlin, M. Kidd, and T. Hinoue, “Of Fibiger and Fables: a cautionary tale of cockroaches and Helicobacter pylori,” Journal of Clinical Gastroenterology, vol. 33, no. 3, pp. 177–179, 2001.
[3]
B. Gryseels, K. Polman, J. Clerinx, and L. Kestens, “Human schistosomiasis,” The Lancet, vol. 368, no. 9541, pp. 1106–1118, 2006.
[4]
A. Yosry, “Schistosomiasis and neoplasia,” Contributions to Microbiology, vol. 13, pp. 81–100, 2006.
[5]
A. Fenwick, L. Savioli, D. Engels, N. R. Bergquist, and M. H. Todd, “Drugs for the control of parasitic diseases: current status and development in schistosomiasis,” Trends in Parasitology, vol. 19, no. 11, pp. 509–515, 2003.
[6]
S. Salem, R. E. Mitchell, A. El-Alim El-Dorey, J. A. Smith, and D. A. Barocas, “Successful control of schistosomiasis and the changing epidemiology of bladder cancer in Egypt,” BJU International, vol. 107, no. 2, pp. 206–211, 2011.
[7]
D. Ziech, R. Franco, A. G. Georgakilas et al., “The role of reactive oxygen species and oxidative stress in environmental carcinogenesis and biomarker development,” Chemico-Biological Interactions, vol. 188, no. 2, pp. 334–339, 2010.
[8]
H. Tanaka and M. Tsuji, “From discovery to eradication of Schistosomiasis in Japan: 1847–1996,” International Journal for Parasitology, vol. 27, no. 12, pp. 1465–1480, 1997.
[9]
A. G. P. Ross, P. B. Bartley, A. C. Sleigh et al., “Schistosomiasis,” The New England Journal of Medicine, vol. 346, no. 16, pp. 1212–1220, 2002.
[10]
R. M. Dimmette, A. M. Elwi, and H. F. Sproat, “Relationship of schistosomiasis to polyposis and adenocarcinoma of large intestine,” American Journal of Clinical Pathology, vol. 26, pp. 266–276, 1959.
[11]
“Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7–14 June 1994,” IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, International Agency for Research on Cancer, vol. 61, pp. 1–241, 1994.
[12]
F. Al-Mashat, A. Sibiany, A. Radwi et al., “Rectal cancer associated with schistosomiasis: report of two cases and review of the literature,” Annals of Saudi Medicine, vol. 21, no. 1-2, pp. 65–67, 2001.
[13]
W. C. Li, Z. G. Pan, and Y. H. Sun, “Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum: a case report,” World Journal of Gastroenterology, vol. 12, no. 37, pp. 6077–6079, 2006.
[14]
A. R. Bharti, N. Weidner, and S. Ramamoorthy, “Chronic schistosomiasis in a patient with rectal cancer,” The American Journal of Tropical Medicine and Hygiene, vol. 80, no. 1, pp. 1–2, 2009.
[15]
M. Canepa, P. T. Fanta, N. Weidner, and M. R. Peterson, “Schistosomiasis and signet ring cell carcinoma of the rectum,” Annals of Diagnostic Pathology. In press.
[16]
Z. R. Guo, Y. C. Ni, and J. L. Wu, “Epidemiological study on relationship between schistosomiasis and colorectal cancer,” Jiangsu Medical Journal, vol. 4, p. 35, 1984.
[17]
B. Q. Liu, Z. P. Rong, X. T. Sun, Y. P. Wu, and R. Q. Gao, “Geographical correlation between colorectal cancer and schistosomiasis in China,” Acta Academiae Medicinae Sinicae, vol. 5, no. 3, pp. 173–177, 1983.
[18]
Z. Xu and D. L. Su, “Schistosoma japonicum and colorectal cancer: an epidemiological study in the People's Republic of China,” International Journal of Cancer, vol. 34, no. 3, pp. 315–318, 1984.
[19]
Y. Li, “Geographical correlation analysis between schistosomiasis and large intestine cancer,” Zhonghua Liu Xing Bing Xue Za Zhi, vol. 9, no. 5, pp. 265–268, 1988.
[20]
J. S. Chen, T. C. Campbell, J. Y. Li, and R. Peto, Diet, Life-Style and Mortality in China: A Study of the Characteristics of 65 Chinese Counties, Oxford University Press, 1990.
[21]
T. Amano, “Clinicopathological studies on the gastro-intestinal schistosomiasis in the endemic area of Yamanashi prefecture, with special reference to the carcinogenicity of schistosome infection,” Japanese Journal of Parasitology, vol. 29, no. 4, pp. 305–312, 1980.
[22]
D. C. Qiu, A. E. Hubbard, B. Zhong, Y. Zhang, and R. C. Spear, “A matched, case-control study of the association between Schistosoma japonicum and liver and colon cancers, in rural China,” Annals of Tropical Medicine and Parasitology, vol. 99, no. 1, pp. 47–52, 2005.
[23]
K. Shindo, “Significance of Schistosomiasis japonica in the development of cancer of the large intestine: report of a case and review of the literature,” Diseases of the Colon and Rectum, vol. 19, no. 5, pp. 460–469, 1976.
[24]
M. C. Chen, C. Y. Chuang, P. Y. Chang, and J.-C. Hu, “Evolution of colorectal cancer in schistosomiasis. Transitional mucosal changes adjacent to large intestinal carcinoma in colectomy specimens,” Cancer, vol. 46, no. 7, pp. 1661–1675, 1980.
[25]
M. C. Chen, C. Y. Chuang, F.-P. Wang, et al., “Colorectal cancer and schistosomiasis,” The Lancet, vol. 1, no. 8227, pp. 971–973, 1981.
[26]
M. P. Rosin, W. A. Anwar, and A. J. Ward, “Inflammation, chromosomal instability, and cancer: the schistosomiasis model,” Cancer Research, vol. 54, no. 7, supplement, pp. 1929s–1933s, 1994.
[27]
A. Ishii, H. Matsuoka, T. Aji et al., “Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review,” Mutation Research, vol. 305, no. 2, pp. 273–281, 1994.
[28]
A. Ishii, H. Matsuoka, T. Aji et al., “Evaluation of the mutagenicity and the tumor-promoting activity of parasite extracts: Schistosoma japonicum and Clonorchis sinensis,” Mutation Research, vol. 224, no. 2, pp. 229–233, 1989.
[29]
K. R. Zalata, W. A. Nasif, S. C. Ming et al., “p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt,” Cellular Oncology, vol. 27, no. 4, pp. 245–253, 2005.
[30]
R. Zhang, S. Takahashi, S. I. Orita et al., “p53 gene mutations in rectal cancer associated with Schistosomiasis japonica in Chinese patients,” Cancer Letters, vol. 131, no. 2, pp. 215–221, 1998.
[31]
A. H. Abd El Hameed, O. E. Negm, O. M. El-Gamal, H. E. Hamouda, K. A. El Nouby, and G. M. Ismail, “Genetic polymorphism of glutathione S-transferases M1 and T1 in Egyptian patients with bilharzial bladder cancer,” Urologic Oncology: Seminars and Original Investigations, vol. 28, no. 3, pp. 296–301, 2010.
[32]
E. S. El Desoky, Y. M. AbdelSalam, R. H. Salama et al., “NAT2*5/*5 genotype (341T>C) is a potential risk factor for schistosomiasis-associated bladder cancer in Egyptians,” Therapeutic Drug Monitoring, vol. 27, no. 3, pp. 297–304, 2005.
[33]
F. Iida, R. Iida, H. Kamijo et al., “Chronic Japanese schistosomiasis and hepatocellular carcinoma: ten years of follow-up in Yamanashi Prefecture, Japan,” Bulletin of the World Health Organization, vol. 77, no. 7, pp. 573–581, 1999.
[34]
T. Amano and T. Oshima, “Hepatoma formation in ddY mice with chronic Schistosomiasis japonica,” Japanese Journal of Cancer Research, vol. 79, no. 2, pp. 173–180, 1988.
[35]
P. Zanger, W. Habscheid, P. G. Kremsner, and H. H. Dahm, “Schistosoma japonicum infection and rectal carcinoid tumour: underreported coincidence or neglected association?” Epidemiology and Infection, vol. 138, no. 9, pp. 1289–1291, 2010.
[36]
Y. Jiang, H. Liu, H. Long, Y. Yang, D. Liao, and X. Zhang, “Goblet cell carcinoid of the appendix: a clinicopathological and immunohistochemical study of 26 cases from Southwest China,” International Journal of Surgical Pathology, vol. 18, no. 6, pp. 488–492, 2010.
[37]
N. Ohtake, O. Takayama, A. Uno, Y. Kubota, S. Shimada, and K. Tamaki, “A case of cutaneous squamous cell carcinoma associated with sporadic porphyria cutanea tarda due to liver disorder after Schistosoma japonicum infection,” Journal of Dermatology, vol. 18, no. 4, pp. 240–244, 1991.
[38]
D. A. Schwartz, “Malignant schwannoma occurring with Schistosoma japonicum: a case report,” The Southeast Asian Journal of Tropical Medicine and Public Health, vol. 13, no. 4, pp. 601–605, 1982.
[39]
A. Sekiguchi, G. Shindo, H. Okabe, N. Aoyanagi, A. Furuse, and T. Oka, “A case of metastatic lung tumor of the colon cancer with ova of Schistosoma japonicum in the resected lung specimen,” Kyobu Geka, vol. 42, no. 12, pp. 1025–1028, 1989.
[40]
K. M. Zhou, “Breast cancer associated with breast schistosomiasis. A case report,” National Medical Journal of China, vol. 63, p. 375, 1983.
[41]
S. Uthman, B. Farhat, S. Farah, and M. Uwayda, “Association of Schistosoma mansoni with colonic carcinoma,” The American Journal of Gastroenterology, vol. 86, no. 9, pp. 1283–1284, 1991.
[42]
E. A. Ameh and P. T. Nmadu, “Colorectal adenocarcinoma in children and adolescents: a report of 8 patients from Zaria, Nigeria,” West African Journal of Medicine, vol. 19, no. 4, pp. 273–276, 2000.
[43]
O. E. H Salim, H. K. S. Hamid, S. O. Mekki, S. H. Suleiman, and S. Z. Ibrahim, “Colorectal carcinoma associated with schistosomiasis: a possible causal relationship,” World Journal of Surgical Oncology, vol. 8, article no. 68, 2010.
[44]
A. R. E. S. Mohamed, M. A. Al Karawi, and M. I. Yasawy, “Schistosomal colonic disease,” Gut, vol. 31, no. 4, pp. 439–442, 1990.
[45]
K. M. Madbouly, A. J. Senagore, A. Mukerjee et al., “Colorectal cancer in a population with endemic Schistosoma mansoni: is this an at-risk population?” International Journal of Colorectal Disease, vol. 22, no. 2, pp. 175–181, 2007.
[46]
A. S. Soliman, M. L. Bondy, S. A. El-Badawy et al., “Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients,” British Journal of Cancer, vol. 85, no. 7, pp. 1037–1046, 2001.
[47]
A. Bacelar, L. G. M. C. Castro, A. C. de Queiroz, and E. Cafe, “Association between prostate cancer and schistosomiasis in young patients: a case report and literature review,” The Brazilian Journal of Infectious Diseases, vol. 11, no. 5, pp. 520–522, 2007.
[48]
H. J. Kahn, B. J. Stroud, and A. V. Berry, “Schistosoma mansoni worm in ovarian cystic teratoma. A case report,” South African Medical Journal, vol. 54, no. 16, pp. 673–674, 1978.
[49]
R. M. Arruda, R. D. A. Castro, M. V. Tamura, J. M. Ruano, E. C. Baracat, and M. Gir？o, “Mansoni's schistosomiasis of a leiomyoma: case report,” Clinics, vol. 62, no. 4, pp. 529–530, 2007.
[50]
L. H. M. R. Coelho, G. Carvalho, and J. M. Carvalho, “Carcinoma in situ and invasive squamous cell carcinoma associated with schistosomiasis of the uterine cervix. A report of three cases,” Acta Cytologica, vol. 23, no. 1, pp. 45–48, 1979.
[51]
V. L. Pannain, J. V. Passos, A. da Rocha Filho, C. Villela-Nogueira, and A. Caroli-Bottino, “Agressive inflammatory myofibroblastic tumor of the liver with underlying schistosomiasis: a case report,” World Journal of Gastroenterology, vol. 16, no. 33, pp. 4233–4236, 2010.
[52]
P. Lewthwaite, G. V. Gill, C. A. Hart, and N. J. Beeching, “Gastrointestinal parasites in the immunocompromised,” Current Opinion in Infectious Diseases, vol. 18, no. 5, pp. 427–435, 2005.
[53]
F. H. Pilsczek, “Helminthic infections mimicking malignancy: a review of published case reports,” Journal of Infection in Developing Countries, vol. 4, no. 7, pp. 425–429, 2010.
[54]
B. R. Mhlanga, L. O. Lanoie, H. J. Norris, E. E. Lack, and D. H. Connor, “Amebiasis complicating carcinomas: a diagnostic dilemma,” American Journal of Tropical Medicine and Hygiene, vol. 46, no. 6, pp. 759–764, 1992.
[55]
R. Gupta, A. Khanduri, D. K. Agarwal, V. Sawlani, S. Baijal, and G. Choudhuri, “Biliary ascariasis associated with periampullary carcinoma,” Indian Journal of Gastroenterology, vol. 14, no. 3, pp. 102–103, 1995.
[56]
T. F. Toufeeq Khan and S. Muniandy, “Biliary ascariasis and extrahepatic cholangiocarcinoma,” Singapore Medical Journal, vol. 36, no. 5, p. 570, 1995.
[57]
T. K. Chowdhury and S. K. Dubey, “Periampullary carcinoma following biliary ascariasis—a case report,” Indian Journal of Cancer, vol. 34, no. 3, pp. 136–138, 1997.
[58]
S. Mineta, K. Shimanuki, A. Sugiura et al., “Chronic anisakiasis of the ascending colon associated with carcinoma,” Journal of Nippon Medical School, vol. 73, no. 3, pp. 169–174, 2006.
[59]
H. J. Yoo, S. H. Kim, J. M. Lee, M. A. Kim, J. K. Han, and B. I. Choi, “The association of anisakiasis in the ascending colon with sigmoid colon cancer: CT colonography findings,” Korean Journal of Radiology, vol. 9, supplement, pp. S56–S60, 2008.
[60]
M. Furukawa, L. Lee, T. Ikegami et al., “Giardiasis in the pancreas accompanied by pancreatic cancer,” Pancreas, vol. 40, no. 1, pp. 168–169, 2011.
[61]
A. Kurita, H. Maguchi, K. Takahashi et al., “Small pancreatic cancer with giardiasis: a case report,” Pancreas, vol. 39, no. 6, pp. 943–945, 2010.
[62]
G. D. Eslick, “Infectious causes of Esophageal cancer,” Infectious Disease Clinics of North America, vol. 24, no. 4, pp. 845–852, 2010.
[63]
N. M. Matsuda, S. M. Miller, and P. R. B. Evora, “The chronic gastrointestinal manifestations of chagas disease,” Clinics, vol. 64, no. 12, pp. 1219–1224, 2009.
[64]
H. Akgül, M. Tez, A. E. Unal, M. Ke？kek, I. Sayek, and T. Oz？elik, “Echinococcus against cancer: why not?” Cancer, vol. 98, no. 9, pp. 1999–2000, 2003.
