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The epidemiology of non-Hodgkin's lymphoma

Abstract

The incidence of non-Hodgkin's lymphoma (NHL) has doubled over the past two decades in the US and most other westernized countries. While improved cancer reporting, changes in lymphoma classification, and increases in AIDS-associated lymphomas have contributed to the startling escalation of disease incidence, these factors are estimated to account for only about 50% of the increase in observed incidence. The elucidation of etiologic factors and their mechanistic role in the pathogenesis of this malignancy are critical to advancements in disease prevention and treatment. Current evidence suggests that factors/conditions that precipitate either chronic antigenic stimulation or immunosuppression may provide a preferential milieu for development of NHL. High rates of lymphoma have been observed among individuals with autoimmune disease, organ transplants, and primary or acquired immunodeficiencies. Ultraviolet radiation, previously demonstrated to have an immunosuppressive effect, has also been suggested as a possible risk factor for NHL. Several pathogens have been linked to the risk of lymphoma, including Epstein–Barr virus, human immunodeficiency virus, human T-cell lymphotropic virus-1, Helicobacter pylori, hepatitis C, and simian virus 40. Whether these microbes are responsible for specific genetic mutations that initiate tumor growth, antigenic stimulation leading to B-cell proliferation, and increased potential of random cell replication errors, or immunosuppression, which thereby promotes tumor growth, has not been clearly delineated. Other exogenous factors which have been implicated in lymphomagenesis are chemicals and agricultural exposures, hair dyes, and blood transfusions. We must build on our current knowledge regarding the etiology of NHL in order that prevention, treatment, and ultimately, cure of this malignancy becomes a reality.

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References

  • Ambinder RF, Lemas MV, Moore S, Yang J, Fabian D and Krone C . (1999). Cancer Treat. Res., 99, 27–45.

  • American Cancer Society (2001). Cancer Facts and Figures. American Cancer Society: Atlanta.

  • American Cancer Society (2004). Cancer Facts and Figures. American Cancer Society: Atlanta.

  • Baecklund E, Ekbom A, SparĂ©n P, Feltelius N and Klareskog L . (1998). Br. Med. J., 317, 180–181.

  • Banks PM . (1992). Cancer Res., 52 (Suppl), 5453s–54535s.

  • Biggar RJ, Frisch M, Engels EA and Goedert JJ . (2001). J. Acquir. Immune Defic. Syndrome, 26, 371–376.

  • Blair A and Zahm SH . (1991). Med. State Art. Rev., 6, 335–354.

  • Blomberg J, Möller T, Olsson H, Anderson H and Jonsson M . (1993). Eur. J. Cancer, 29A, 2101–2105.

  • Breslin P, Kang HK, Lee Y, Burt V and Shepard BM . (1988). J. Occup. Med., 30, 412–419.

  • Cerhan JR, Wallace RB, Dick F, Kemp J, Parker AS, Zheng W, Sellers TA and Folsom AR . (2001). Cancer Epidemiol. Biomarkers Prev., 10, 361–368.

  • Cerhan JR, Wallace RB, Folsom AR, Potter JD, Munger RG and Prineas RJ . (1993). Ann. Intern. Med., 119, 8–15.

  • Chiu BCH, Cerhan JR, Gapstur SM, Sellers TA, Zheng W, Lutz CT, Wallace RB and Potter JD . (1999). Br. J. Cancer, 80, 1476–1482.

  • Cinque P, Brytting M, Wahren B, Linde A, Cinque P, Castagna A, Lazzarin A, Vago L, Parravicini C, Zanchetta N and Monforte AD . (1993). Lancet, 342, 398–401.

  • Cleary ML and Sklar J . (1984). Lancet, ii, 489–493.

  • Cleghorn FR, Manns A, Falk R, Hartge P, Hanchard B, Jack N, Williams E, Jaffe E, White F and Bartholomew C . (1995). J. Natl. Cancer Inst., 87, 1009–1014.

  • D'Amore F, Hasle H and Hansen KS . (1992). Hematol. Rev., 6, 183–199.

  • David H, Mendoza S, Konishi T and Miller C . (2001). Cancer Lett., 162, 57–64.

  • Del Maso L and Franceschi S . (2003). Lancet Oncol., 4, 110–116.

  • De Re V, De Vita S, Marzotto A, Rupolo M, Gloghini A, Pivetta B, Gasparotto D, Carbone A and Boiocchi M . (2000). Blood, 96, 3578–3584.

  • Devesa SS and Fears T . (1992). Cancer Res., 52 (Suppl), 5432s–54340s.

  • De Vita S, Sacco C, Sanconno D, Gloghini A, Dammacco F, Crovatto M, Santini G, Dolcetti R, Boiocchi M, Carbone A and Zagonel V . (1997). Blood, 90, 776–782.

  • Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS and Biggar RJ . (2002). J. Natl. Cancer Inst., 94, 1204–1210.

  • Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell'Oro S, Fleischhauer K, Caggiari L, Lettini AA, Dal Cin E, Ieri R, Freschi M, Villa E, Boiocchi M and Dolcetti R . (2004). J. Nat. Cancer Inst., 96, 586–594.

  • Filipovich AH, Mathur A, Kamat D and Shapiro RS . (1992). Cancer Res., 52, 5465s–5467s.

  • Fisher MS and Kripke ML . (1982). Science, 216, 1133–1134.

  • Gaidano G and Dalla-Favera R . (1997). Cancer Principles & Practice of Oncology Vol. 3. DeVita V Jr, Hellman S and Rosenberg SA. (eds). Lippincott-Raven: Philadelphia, NY, pp. 2131–2145.

    Google Scholar 

  • Garabrant DH and Philbert MA . (2002). Crit. Rev. Toxicol., 32, 233–257.

  • Gisbert JP, Garcia-Buey L, Pajares JM and Moreno-Otero R . (2003). Gastroenterology, 125, 1723–1732.

  • Goedert JJ . (2000). Semin. Oncol., 27, 390–401.

  • Greenlee R, Hill-Harmon M, Murray T and Thun M . (2001). CA: Cancer J. Clin., 51, 15–36.

  • Grogan T and Miller T . (1995). Cancer Treatment Haskell CM (ed). WB Saunders: Philadelphia, 979–1005.

    Google Scholar 

  • Groves FD, Linet MS, Travis LB and Devesa SS . (2000). J. Natl. Cancer Inst., 92, 1240–1251.

  • Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA and Bloomfield CD . (1999). Ann. Oncol., 10, 1419–1432.

  • Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B and Gatter KC . (1994). Blood, 84, 1361.

  • Harris OD, Cooke WT, Thompson H and Waterhouse JAH . (1967). Am. J. Med., 42, 899.

  • Hartge P and Devesa SS . (1992). Cancer Res., 52, 5566s–5569s.

  • Hayes HM, Tarone RE and Cantor KP . (1991). J. Natl. Cancer Inst., 83, 1226–1231.

  • Hoar SK, Blair A and Holmes FF . (1986). JAMA, 256, 1141–1147.

  • Holford TR, Zheng T, Mayne ST and McKay LA . (1992). Cancer Res., 52, 5443s–5446s.

  • Holly EA, Lele C, Bracci PM and McGrath MS . (1999). Am. J. Epidemiol., 150, 375–389.

  • Hoover RN . (1992). Cancer Res., 52, 5477S.

  • Hussell T, Isaacson P, Crabtree J and Spencer J . (1993). Lancet, 342, 571.

  • Hussell T, Isaacson PG, Crabtree JE and Spencer J . (1996). J. Pathol., 178, 122–127.

  • International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans (1978). Some Aromatic Amines and Related Nitro Compounds – Hair Dyes, Colouring Agents and Miscellaneous Industrial Chemicals. Monograph 16. International Agency for Research on Cancer: Lyon, France.

  • International Agency for Research on Cancer Working Group on the Evaluation of Carcinogenic Risks to Humans (1996). Human Immunodeficiency Viruses and Human T-cell Lymphotropic Viruses. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 67 IARC Press: Lyon, pp. 67.

  • International Agency for Research on Cancer (1997). Epstein–Barr Virus and Kaposi's Sarcoma Herpesvirus/Herpesvirus 8. Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC: Lyon.

  • Jacobson LP, Yamashita TE, Detels R, Margolick JB, Chmiel JS, Kingsley LA, Melnick S and Munoz A . (1999). J. Acquir. Immune Defic. Syndrome, 21 (Suppl 1), S34–S41.

  • Jeevan A and Kripke ML . (1990). Cell Immunol., 130, 32–41.

  • Jonsson V, Wiik A, Hou-Jensen K, Christiansen M, Ryder LP, Madsen HO, Geisler C, Hansen MM, Thomsen K, Vorstrup S and Svejgaard A . (1999). J. Intern. Med., 245, 277–286.

  • Kamel OW, van de Rijn M, Hanasono MM and Warnke RA . (1995). Leukemia Lymph., 16, 363.

  • Kast WM, Schreiber H and Velders MP . (1998). Encyclopedia of Life Sciences. Macmillan Reference Ltd: UK.

    Google Scholar 

  • Kinlen L . (1992). Cancer Res., 52, 5474s–5476s.

  • Kirkley SA, Cowles J, Pellegrini Jr VD, Harris CM, Boyd AD and Blumberg N . (1995). Lancet, 345, 527.

  • Klein HG . (1999). Anesthesiology, 91, 861–865.

  • Kripke ML . (1994). Cancer Res., 54, 6102–6105.

  • Landers DF, Hill GE, Wong KC and Fox IJ . (1996). Anesth. Analg., 82, 187–204.

  • Lecuit M, Abachin E, Martin A, Poyart C, Pochart P, Suarez F, Bengoufa D, Feuillard J, Lavergne A, Gordon JI, Berche P, Guillevin L and Lortholary O . (2004). N. Engl. J. Med., 350, 239–248.

  • Levi F, Randimbison L, Te VC and La Vecchia C . (1996). Br. J. Cancer, 74, 1847–1850.

  • Levine AM . (1994). Ann. Oncol., 5, 29.

  • Linet MS and Pottern LM . (1992). Cancer Res., 52, 5468s–5473s.

  • Luppi M, Longo G, Ferrari MG, Ferrara L, Marasca R, Barozzi P, Morselli M, Emilia G and Torelli G . (1996). Br. J. Haematol., 94, 373–375.

  • McMichael AJ and Giles GG . (1996). Br. J. Cancer, 73, 945–950.

  • Melbye M, Adami HO, Hjalgrim H and Glimelius B . (1996). Acta Oncol., 35, 655–657.

  • Melbye M and Trichopoulos D . (2002). Textbook of Cancer Epidemiology Vol. 25. Adami H-O, Hunter D and Trichopoulos D (eds). Oxford University Press: Oxford, pp. 535–555.

    Google Scholar 

  • Memon A and Doll R . (1994). Int. J. Cancer, 58, 366–368.

  • Moore RD and Chiasson RE . (1999). AIDS, 13, 1933–1942.

  • Morrow RH, Kisuule A, Pike MC and Smith PG . (1976). J. Nat. Cancer Inst., 56, 479–483.

  • Morton LM, Hartge P, Cerhan JR, Holly EA, Holford TR, Mayne ST and Zheng T . (2004). Proc. AACR, 45, 490.

  • Mueller NE, Mohar A and Evans A . (1992). Cancer Res., 52 (Suppl), 5479s–5481s.

  • Murphy EL, Figueroa JP, Gibbs WN, Holding-Cobham M, Cranston B, Malley K, Bodner AJ, Alexander SS and Blattner WA . (1991). Am. J. Epidemiol., 133, 1114–1124.

  • Nakatsuka S, Lin A, Dong Z, Nomura S, Takakuwa T, Miyazato H, Aozasa K and Osaka Lymphoma Study Group. (2003). Cancer Res., 63, 7606–7608.

  • Nelson RA, Levine AM, Marks G and Berstein L . (1997). Br. J. Cancer, 76, 1532–1537.

  • Offit K, Wong G, Filippa DA, Tao Y and Chaganti RSK . (1991). Blood, 77, 1508.

  • Opelz G and Henderson R . (1993). Lancet, 342, 1514–1516.

  • Opelz G, Sengar DP, Mickey MR and Terasaki PI . (1973). Transplant. Proc., 5, 253–259.

  • Palackdharry CS . (1994). Oncology, 8, 67–73.

  • Palella Jr FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ and Holmberg SD . (1998). N. Engl. J. Med., 338, 853–860.

  • Paltiel O, Schmit T, Adler B, Rachmilevitz EA, Polliack A, Cohen A, Haim N, Shachar MB, Epelbaum R, Barchana M, Cohen R and Ben Yehuda D . (2000). Cancer, 88, 2357–2366.

  • Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH and Friedman GD . (1994). N. Engl. J. Med., 330, 1267–1271.

  • Pearce N . (1989). Br. J. Ind. Med., 46, 143–144.

  • Pettersson T, Pukkala E, Teppo L and Friman C . (1992). Ann. Rheum. Dis., 51, 437–439.

  • Pimental D, McLaughlin L and Zepp A . (1993). Handbook of Pest Management in Agriculture Pimental D (ed), Vol. 1 CRC Press: Boca Rotan, pp. 679–680.

    Google Scholar 

  • Rabkin CS, Biggar RJ and Horm JW . (1991). Int. J. Cancer, 47, 692–696.

  • Reed DM . (1902). Johns Hopkins Hosp. Rev., 10, 133.

  • Ries L, Eisner M, Kosary C, Hankey B, Miller B, Clegg L and Edwards B (eds) (2001). SEER Cancer Statistics Review. National Cancer Institute: Bethesda, MD, 1973–1998.

    Google Scholar 

  • Rivas JM and Ullrich SE . (1992). J. Immunol., 149, 3865–3871.

  • Rizzo P, Carbone M, Fisher SG, Matker C, Swinnen LJ, Powers A, Di Resta I, Alkan S, Pass HI and Fisher RI . (1999). Chest, 166 (Suppl), 470S–473S.

  • SEER (2003). Surveillance, Epidemiology & End Results Program Public-Use Data 1973–2000, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch (released May).

  • Selik RM, Starcher ET and Curran JW . (1987). AIDS, 1, 175–182.

  • Shipp MA, Mauch PM and Harris NL . (1997). Cancer Principles & Practice of Oncology Vol. 3. DeVita Jr V, Hellman S and Rosenberg SA (eds). Lippincott-Raven: Philadelphia, New York, pp. 2165–2220.

    Google Scholar 

  • Shivapurkar N, Harad K, Reddy J, Scheuermann RH, Xu Y, McDenna RW, Michgrub S, Kroft SH, Feng Z and Gasdar AF . (2002). Lancet, 359, 851–852.

  • Swinnen L, Costanzo-Nordin MR, Fisher SG, O'Sullivan EJ, Johnson MR, Heroux AL, Dizikes GJ, Pifarre R and Fisher RI . (1990). N. Engl. J. Med., 323, 1723.

  • Takatsuki K, Uchiyama T, Sagawa K and Yodoi J . (1976). Topics in Hematology, Adult T Cell Leukemia in Japan. Seno S, Takaku F, Iron S (eds). Excerpta Medica: Amsterdam, pp. 73–78.

    Google Scholar 

  • Tavani A, La Vecchia C, Franceschi S, Serraino D and Carbone A . (2000). Eur. J. Cancer Prev., 9, 59–64.

  • Tycko B and Sklar J . (1990). Cancer Cells, 2, 1.

  • Vermeer M and Streilein JW . (1990). Photodermatol. Photoimmunol./Photomed., 7, 258–265.

  • Vilchez RA, Madden CR, Kozinetz CA, Halvorson SJ, White ZS, Jorgensen JL, Finch CJ and Butel JS . (2002). Lancet, 359, 817–823.

  • Vink AA, Yarosh DB and Kripke ML . (1996). Photochem. Photobiol., 63, 383–386.

  • Wahl SM, Wilder RL, Katona IM, Wahl LM, Allen JB, Scher I and Decker JL . (1983). Arthritis Rheum., 26, 1076–1084.

  • Wiernik PH, Wang SQ, Hu XP, Marino P and Paietta E . (2000). Br. J. Haematol., 108, 72–79.

  • Wigle DT, Semenciw RM, Wilkins K, Riedel D, Ritter L, Morrison HI and Mao Y . (1990). J. Natl. Cancer Inst., 82, 575–582.

  • Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, Diaz-PerĂ©z JL, Geerts ML, Goos M, Knobler R, Ralfkiaer E, Santucci M, Smith N, Wechsler J, van Vloten WA and Meijer CJLM . (1997). Blood, 90, 354–371.

  • Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR and Isaacson PG . (1991). Lancet, 338, 1175–1176.

  • Ye BH . (2002). Cancer Investig., 18, 356–365.

  • Yosida M, Kiyokawa T, Watanabe T, Hattori S, Fujisawa J-I and Seiki M . (1985). Retroviruses in Human Lymphoma/Leukemia. Miwa M (ed). Scientific Societies Press: Tokyo, Japan, pp. 39–47.

    Google Scholar 

  • Zahm SH, Weisenburger DD and Babbitt PA . (1990). Epidemiology, 1, 349–356.

  • Zahm SH, Weisenburger DD, Holmes FF, Cantor KP and Blair A . (1997). Cancer Causes Control, 8, 159–166.

  • Zhang Y, Holford TR, Leaderer B, Boyle P, Zahm SH, Flynn S, Tallini G, Owens PH and Zheng T . (2004). Am. J. Epidemiol., 159, 148–154.

  • Zheng T, Mayne ST, Boyle P, Holford Tr, Liu WL and Flannery J . (1992). Cancer, 70, 840–849.

  • Zhu K, Levine RS, Gu Y, Brann EA, Hall I, Caplan LS and Baum MK . (1998). Cancer Causes Control, 9, 77–82.

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Fisher, S., Fisher, R. The epidemiology of non-Hodgkin's lymphoma. Oncogene 23, 6524–6534 (2004). https://doi.org/10.1038/sj.onc.1207843

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