title: Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. The late stage of MPM diagnosis and the long latency that exist between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects.
  
  
  METHODS
  This manuscript is a review of current literature about the pathogenesis of malignant mesothelioma. In this overview, current published studies concerning pathogenesis of malignant mesothelioma are reviewed, with insights into its etiology and pathogenesis. We searched pubmed using the following subjects: mesothelioma, radiation, genetics, pediatric malignant mesothelioma, SV40 virus, and growth factors. We selected 350 valuable articles of which 152 sources were used to complete this review.
  
  
  CONCLUSIONS
  Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. In this review, we discuss the current molecular and genetic contributors to MPM pathogenesis and the risk factors associated with these carcinogenic processes.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH, USA.
authors.forename: Shoshana J
authors.initials: SJ
authors.lastname: Weiner
authors.forename: Siyamek
authors.initials: S
authors.lastname: Neragi-Miandoab
mesh_terms: D004777:Environment; D020022:Genetic Predisposition to Disease; D006801:Humans; D008654:Mesothelioma / Q000209:etiology* / Q000235:genetics; D016066:Pleural Effusion, Malignant / Q000209:etiology* / Q000235:genetics
references.citation: J Cutan Pathol. 2000 Sep;27(8):419-22
references.pmid: 10955690
references.citation: Cell. 1999 Jun 11;97(6):684-6; discussion 686-8
references.pmid: 10380921
references.citation: J Pathol. 2001 Apr;193(4):468-75
references.pmid: 11276005
references.citation: J Mol Med (Berl). 1996 Oct;74(10):589-607
references.pmid: 8912180
references.citation: Cancer Control. 2006 Oct;13(4):255-63
references.pmid: 17075562
references.citation: Crit Rev Toxicol. 2006 Feb;36(2):165-87
references.pmid: 16736942
references.citation: Nat Rev Mol Cell Biol. 2004 Nov;5(11):897-907
references.pmid: 15520809
references.citation: Ann N Y Acad Sci. 1991 Dec 31;643:258-70
references.pmid: 1809138
references.citation: J Natl Cancer Inst. 1972 Mar;48(3):797-821
references.pmid: 5058974
references.citation: Cancer. 2007 Apr 15;109(8):1454-61
references.pmid: 17348013
references.citation: Rev Environ Health. 1999 Jan-Mar;14(1):11-20
references.pmid: 10372416
references.citation: Hum Pathol. 1998 Dec;29(12):1382-92
references.pmid: 9865823
references.citation: Oncogene. 2002 Jun 20;21(27):4340-4
references.pmid: 12082623
references.citation: Genes Chromosomes Cancer. 2000 Jul;28(3):337-41
references.pmid: 10862040
references.citation: Oncogene. 1994 Jun;9(6):1781-90
references.pmid: 8183577
references.citation: Med Lav. 1995 Sep-Oct;86(5):426-34
references.pmid: 8684292
references.citation: Cancer. 1988 May 15;61(10):2019-21
references.pmid: 3282640
references.citation: Thorax. 1991 Jun;46(6):463-4
references.pmid: 1858091
references.citation: Int J Cancer. 2007 Jul 1;121(1):12-20
references.pmid: 17354240
references.citation: Am J Ind Med. 2007 May;50(5):357-69
references.pmid: 17407142
references.citation: Biochem Biophys Res Commun. 2004 Oct 29;323(4):1246-50
references.pmid: 15451431
references.citation: Biochem Biophys Res Commun. 2006 Apr 21;342(4):1228-32
references.pmid: 16516163
references.citation: Curr Opin Pulm Med. 2007 Jul;13(4):334-8
references.pmid: 17534182
references.citation: Br J Cancer. 2003 May 19;88(10):1553-9
references.pmid: 12771921
references.citation: Lab Invest. 1999 Apr;79(4):427-38
references.pmid: 10211995
references.citation: Am J Physiol. 1997 Nov;273(5):L1029-35
references.pmid: 9374731
references.citation: Eur J Cardiothorac Surg. 2006 Jan;29(1):14-9
references.pmid: 16343925
references.citation: Cancer Res. 1987 Mar 15;47(6):1681-6
references.pmid: 3028612
references.citation: Cancer Res. 2006 Mar 15;66(6):2970-9
references.pmid: 16540645
references.citation: Semin Oncol. 2002 Feb;29(1):2-17
references.pmid: 11836664
references.citation: Br J Cancer. 1998 Apr;77(7):1052-9
references.pmid: 9569039
references.citation: J Pathol. 1987 Aug;152(4):309-16
references.pmid: 3668733
references.citation: Cancer. 1985 Jul 15;56(2):273-6
references.pmid: 2988741
references.citation: Semin Cancer Biol. 2001 Feb;11(1):23-30
references.pmid: 11243896
references.citation: Cancer. 1996 Apr 1;77(7):1379-85
references.pmid: 8608519
references.citation: Cell Cycle. 2005 Dec;4(12):1862-9
references.pmid: 16319530
references.citation: Dev Biol Stand. 1998;94:23-32
references.pmid: 9776222
references.citation: Ind Health. 2001 Apr;39(2):183-5
references.pmid: 11341549
references.citation: Thorax. 1996 Nov;51(11):1074-6
references.pmid: 8958887
references.citation: Mutat Res. 2005 Dec 30;592(1-2):36-44
references.pmid: 15993904
references.citation: Semin Thorac Cardiovasc Surg. 1997 Oct;9(4):347-55
references.pmid: 9352951
references.citation: J Cell Physiol. 1999 Aug;180(2):150-7
references.pmid: 10395284
references.citation: J Clin Pathol. 2003 Oct;56(10):728-30
references.pmid: 14514773
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10214-9
references.pmid: 10954737
references.citation: Mutat Res. 2006 Jul 25;599(1-2):124-34
references.pmid: 16564556
references.citation: J Pathol. 1997 Jan;181(1):67-74
references.pmid: 9072005
references.citation: Nat Rev Cancer. 2005 Oct;5(10):773-85
references.pmid: 16195750
references.citation: Genes Chromosomes Cancer. 1995 Feb;12(2):87-96
references.pmid: 7535092
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12032-7
references.pmid: 11572935
references.citation: Oncol Rep. 2005 Sep;14(3):743-50
references.pmid: 16077986
references.citation: Ann Occup Hyg. 2001 Oct;45(7):513-8
references.pmid: 11583653
references.citation: J Pathol. 2000 Jan;190(1):80-5
references.pmid: 10640996
references.citation: Dev Biol Stand. 1998;94:127-36
references.pmid: 9776233
references.citation: J Surg Oncol. 2000 Sep;75(1):42-50
references.pmid: 11025461
references.citation: Int J Cancer. 2001 Mar 1;91(5):638-43
references.pmid: 11267973
references.citation: Cancer Res. 1993 Jan 15;53(2):388-92
references.pmid: 8417831
references.citation: Clin Cancer Res. 2003 Jun;9(6):2108-13
references.pmid: 12796375
references.citation: Cancer Res. 2006 Jan 1;66(1):352-61
references.pmid: 16397249
references.citation: Respir Med. 2007 Mar;101(3):503-9
references.pmid: 16919927
references.citation: J Surg Oncol. 1976;8(5):369-72
references.pmid: 994503
references.citation: Oncogene. 2003 Jan 9;22(1):81-9
references.pmid: 12527910
references.citation: Cancer. 1995 Aug 1;76(3):437-41
references.pmid: 8625125
references.citation: J Thorac Cardiovasc Surg. 1998 Nov;116(5):854-9
references.pmid: 9806392
references.citation: Am J Clin Pathol. 1984 Jul;82(1):15-23
references.pmid: 6588749
references.citation: Am J Med. 2003 Jun 1;114(8):675-84
references.pmid: 12798456
references.citation: Tumori. 2002 Jan-Feb;88(1):1-9
references.pmid: 12004841
references.citation: Am J Med. 1994 Oct;97(4):379-82
references.pmid: 7942942
references.citation: Cancer Res. 1993 Jun 15;53(12):2858-64
references.pmid: 7684950
references.citation: Thorax. 2003 Mar;58(3):198-203
references.pmid: 12612292
references.citation: Lung Cancer. 2006 Feb;51(2):207-15
references.pmid: 16384623
references.citation: Ind Health. 2001 Apr;39(2):57-64
references.pmid: 11341559
references.citation: Oncogene. 1988 Jun;2(6):601-5
references.pmid: 3290807
references.citation: Anticancer Res. 2000 Nov-Dec;20(6C):4745-9
references.pmid: 11205211
references.citation: Oncol Rep. 2002 Sep-Oct;9(5):955-9
references.pmid: 12168054
references.citation: Am J Physiol. 1995 Mar;268(3 Pt 1):L471-80
references.pmid: 7900829
references.citation: Cancer Res. 2005 Sep 15;65(18):8090-5
references.pmid: 16166281
references.citation: J Natl Cancer Inst. 2002 Feb 6;94(3):229-30
references.pmid: 11830615
references.citation: Am J Respir Cell Mol Biol. 1998 Aug;19(2):226-36
references.pmid: 9698594
references.citation: Cancer Res. 1995 Feb 15;55(4):792-8
references.pmid: 7850791
references.citation: Oncogene. 2002 Feb 21;21(9):1434-42
references.pmid: 11857086
references.citation: Lung Cancer. 2002 Nov;38(2):131-6
references.pmid: 12399123
references.citation: Cancer Lett. 2006 Aug 8;239(2):183-9
references.pmid: 16216411
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10397-10402
references.pmid: 16798876
references.citation: Virology. 2004 Jan 5;318(1):1-9
references.pmid: 15015494
references.citation: Carcinogenesis. 2007 Sep;28(9):2047-52
references.pmid: 17434931
references.citation: Cancer Res. 1999 Jan 15;59(2):450-4
references.pmid: 9927061
references.citation: Cancer. 1984 Jul 15;54(2):367-9
references.pmid: 6327010
references.citation: J Pathol. 2003 Nov;201(3):355-62
references.pmid: 14595746
references.citation: Cancer Lett. 2004 Nov 8;215(1):1-20
references.pmid: 15374627
references.citation: Chest. 2005 Nov;128(5):3382-7
references.pmid: 16304288
references.citation: Exp Lung Res. 2001 Oct-Nov;27(7):605-16
references.pmid: 11597120
references.citation: J Clin Oncol. 1996 Jul;14(7):2098-100
references.pmid: 8683242
references.citation: Int J Cancer. 2007 Jun 15;120(12):2739-43
references.pmid: 17290392
references.citation: N Engl J Med. 2005 May 5;352(18):1929-30
references.pmid: 15872213
references.citation: Am J Ind Med. 1988;13(6):639-57
references.pmid: 2839031
references.citation: Int J Biochem Cell Biol. 2006;38(12):2000-4
references.pmid: 16963313
references.citation: Ind Health. 2007 Jun;45(3):379-87
references.pmid: 17634686
references.citation: Chem Biol Interact. 1987;62(1):89-97
references.pmid: 3034439
references.citation: Int J Cancer. 2003 May 1;104(5):603-10
references.pmid: 12594815
references.citation: Nat Cell Biol. 2002 May;4(5):E131-6
references.pmid: 11988758
references.citation: Anticancer Res. 2004 May-Jun;24(3a):1625-30
references.pmid: 15274332
references.citation: Lung Cancer. 2004 Aug;45 Suppl 1:S125-7
references.pmid: 15261445
references.citation: Ann Diagn Pathol. 2006 Aug;10(4):241-50
references.pmid: 16844568
references.citation: Ind Health. 2004 Apr;42(2):235-9
references.pmid: 15128174
references.citation: Cancer Res. 2007 Apr 15;67(8):3637-45
references.pmid: 17440075
references.citation: Semin Cancer Biol. 2001 Feb;11(1):31-8
references.pmid: 11243897
references.citation: Cancer Res. 2005 Apr 1;65(7):2602-9
references.pmid: 15805256
references.citation: J Thorac Cardiovasc Surg. 1999 Jan;117(1):54-63; discussion 63-5
references.pmid: 9869758
references.citation: BMC Genomics. 2007 Mar 01;8:62
references.pmid: 17331233
references.citation: Cancer Res. 1996 Dec 1;56(23):5334-8
references.pmid: 8968079
references.citation: Br J Cancer. 2003 Feb 10;88(3):388-95
references.pmid: 12569381
references.citation: Oncogene. 2004 Aug 26;23(39):6672-6
references.pmid: 15221014
references.citation: Cancer. 1998 Jan 1;82(1):8-34
references.pmid: 9428476
references.citation: Cancer Res. 2006 Nov 15;66(22):10786-94
references.pmid: 17108115
references.citation: Cancer Res. 1998 Oct 15;58(20):4505-9
references.pmid: 9788590
references.citation: Genes Dev. 2000 Aug 1;14(15):1837-51
references.pmid: 10921899
references.citation: Pediatr Pathol. 1992 May-Jun;12(3):333-47
references.pmid: 1384016
references.citation: Ann Plast Surg. 1999 Sep;43(3):313-7
references.pmid: 10490187
references.citation: Cancer Res. 2003 Aug 1;63(15):4547-51
references.pmid: 12907630
references.citation: Int J Oncol. 2001 Feb;18(2):425-33
references.pmid: 11172613
references.citation: Eur Respir J. 1998 Oct;12(4):972-81
references.pmid: 9817178
references.citation: J Cell Biochem. 1999 Dec;76(2):189-93
references.pmid: 10618636
references.citation: Thorax. 1997 Jun;52(6):496-7
references.pmid: 9227712
references.citation: Nat Genet. 1993 Aug;4(4):415-20
references.pmid: 8401592
references.citation: Cancer Res. 2005 Apr 15;65(8):3049-52
references.pmid: 15833832
references.citation: Pediatr Hematol Oncol. 1994 Jul-Aug;11(4):399-408
references.pmid: 7947012
references.citation: Clin Imaging. 1997 May-Jun;21(3):189-94
references.pmid: 9156307
references.citation: Cancer. 1988 Aug 15;62(4):838-47
references.pmid: 3293765
references.citation: Can Assoc Radiol J. 1990 Dec;41(6):384-6
references.pmid: 2257515
references.citation: Toxicol Sci. 2002 Aug;68(2):331-8
references.pmid: 12151629
references.citation: Oncogene. 2006 Sep 28;25(44):5960-8
references.pmid: 16652148
references.citation: J Cell Physiol. 2006 May;207(2):540-52
references.pmid: 16447244
references.citation: Ind Health. 2002 Apr;40(2):175-81
references.pmid: 12064559
references.citation: Cancer Res. 2005 Feb 1;65(3):743-8
references.pmid: 15705870
references.citation: Br J Cancer. 1997;75(4):523-7
references.pmid: 9052404
references.citation: Med Electron Microsc. 2002 Mar;35(1):16-23
references.pmid: 12111403
references.citation: Arch Environ Health. 2003 Apr;58(4):229-32
references.pmid: 14655903
references.citation: Am J Respir Cell Mol Biol. 2002 Feb;26(2):189-93
references.pmid: 11804869
references.citation: Eur J Pediatr Surg. 1993 Dec;3(6):362-5
references.pmid: 8110720
references.citation: J Natl Cancer Inst. 2003 Apr 2;95(7):532-9
references.pmid: 12671021
references.citation: Mutat Res. 2000 Jun 22;468(1):87-92
references.pmid: 10863160
references.citation: Radiographics. 2000 Jan-Feb;20(1):67-81
references.pmid: 10682772
references.citation: Oncogene. 2002 Feb 14;21(8):1141-9
references.pmid: 11850833
references.citation: Am J Clin Pathol. 1986 Aug;86(2):227-30
references.pmid: 3017091
references.citation: Cancer Res. 2005 Jun 15;65(12):5256-62
references.pmid: 15958571
references.citation: Cancer Res. 2002 Nov 1;62(21):6065-9
references.pmid: 12414630
references.citation: Br J Ind Med. 1990 Sep;47(9):615-20
references.pmid: 2169860
references.citation: IARC Sci Publ. 1980;(30):237-46
references.pmid: 7239642