Mul$ple'pes$cide'exposures'and' the'risk'of'mul$ple'myeloma'in' - - PowerPoint PPT Presentation

Mul$ple'pes$cide'exposures'and' the'risk'of'mul$ple'myeloma'in' Canadian'men'

Linda&Kachuri,&Paul&Demers,&Aaron&Blair,&John&Spinelli,& Manisha&Pahwa,&John&McLaughlin,&Punam&Pahwa,& James&Dosman,&Shelley&Harris&

&

UICC&World&Cancer&Congress& August&28,&2012&

Background'

• MulGple&myeloma&(MM)&is&the&2nd&most&common&hematological&

cancer&worldwide,&with&2400&cases&expected&in&Canada&in&20121&

• EGology&of&MM&is&poorly&understood&

– Risk&factors&include:&older&age,&male&gender,&ethnicity& &

• Higher&risk&of&MM&in&agricultural'occupa$ons3,4,5:&

– Excess&risks&partly&aSributed&to&pes$cide'exposure4,5,6& – PosiGve&associaGons&observed&for&certain&herbicides4,5,7&&& – and&insecGcides,&specifically&organochlorines&and& carbamates&4,6,7&

1&Canadian&Cancer&Society:&Canadian&Cancer&StaGsGcs&2012& 2&Alexander&DD,&Mink&PJ,&Adami&HO,&&et&al.&Int&J&Cancer.&2007;120&Suppl&12:40\61.& 3&Lope&V,&Perez\Gomez&B,&Aragones&N,&et&al.&Cancer&Epidemiol&Biomarkers&Prev.&2008;&17(11):3123\7.&& 4&Eriksson&M,&Karlsson&M.&Br&J&Ind&Med.&1992;&49(2):95\103.&& 5&Baris&D,&Silverman&DT,&Brown&LM&et&al.&Scand&J&Work&Environ&Health.&2004;&30(3):215\22.& 6&Nanni&O,&Falcini&F,&Buiad&E&et&al.&Cancer&Causes&Control.&1998;&9(3):277\83& 7&Pahwa&P,&Karunanayake&CP,&Dosman&JA.&J&Agromedicine.&2012;&17(1):40\50&&

Background'

• Why&focus&on&mulGple&pesGcide&exposures?

&&

– More&accurately&reflects&how&exposures&occur&in& agricultural&sedngs& – Focusing&only&on&individual&pesGcides&might&miss&addiGve& effects&from&mulGple&pesGcide&use& – Studies&have&examined&risks&of&non\Hodgkin&lymphoma& from&exposure&to&mulGple&pesGcides&and&pesGcide& combinaGons1,2,&but&this&has&not&been&done&for&MM&

1&De&Roos&AJ,&Zahm&SH,&Cantor&KP&et&al.&Occup&Environ&Med.&2003;&60(9):E11.& 2&Hohenadel&K,&Harris&SA,&McLaughlin&JR&et&al.&Int&J&Environ&Res&Public&Health.&2011;&8(6):2320\30.&&&

&

Objec$ves'

• This&study&extends&previous&analyses&that&examined&risks&of&MM&

among&men&from&exposure&to&individual&pesGcides1&&

• 1. To&invesGgate&the&associaGon&between&self\reported&use&of&

mul$ple'pes$cides'and&the&risk&of&MM&among&men&

• 2. To&examine&commonly&used&pes$cide'combina$ons'with&

the&goal&of&assessing&interacGve&joint&effects&

&

1&Pahwa&P,&Karunanayake&CP,&Dosman&JA.&J&Agromedicine.&2012;&17(1):40\50&

Study'Popula$on'

• Cross\Canada&Study&of&PesGcides&and&Health&(CCSPH):&case@

control'study&conducted&on&males&aged&19&years&and&older&in& six&provinces&between&1991&and&1994&

• Incident'MM'cases'recruited&from&provincial&cancer&registries&

and&hospitals&

• Popula$on'controls'were&idenGfied&through&health&insurance&

records&and&frequency\matched&by&age&(±2&years)&and& province&

QC' ON' MB' SK' AB' BC'

Data'Collec$on'

• Stage'1:'Postal'ques$onnaires''

– informaGon&on&pesGcide&use&& – demographic&characterisGcs& – medical&and&occupaGonal&history&

&

• Stage'2:'Telephone'interviews'with&subjects&reporGng&&≥10&

hours/year&of&pesGcide&use&and'15%&random&sample&of&the& remainder' – detailed&informaGon&on&individual&pesGcide&use&

Mul$ple'Pes$cide'Exposures'

• PesGcides&were&grouped&in&the&following&categories:&&
• 1. Type:'herbicides,&insecGcides,&fungicides&
• 2. Chemical'class:'phenoxy&herbicides,&organochlorines,&
• rganophosphates,&carbamates&
• 3. Carcinogenic'poten$al:'pesGcides&rated&as&“probably&

carcinogenic”&(IARC&2A&or&higher),&and&“possibly& carcinogenic”&(IARC&2B&or&higher)&

• Pes$cide'combina$ons:&2&pesGcides&used&by&the&same&subject&&

Note:&a&composite&carcinogenicity&score&was&created&using&assessments&from&the& IARC&Monographs,&US&Environmental&ProtecGon&Agency&(EPA)&Integrated&Risk& InformaGon&System&(IRIS),&and&the&US&EPA&Office&of&PesGcides&Program&(OPP)&

Sta$s$cal'Analyses'

• LogisGc&regression&was&used&to&calculate&odds&raGos&(OR)&and&

95%&confidence&intervals&(CI)&and&to&obtain&ptrend&

– Models&were&adjusted&for&age,&province&of&residence,&use&of&a&proxy& respondent,&and&smoking&status&

• CombinaGons&of&pesGcides&used&by&20&or&more&parGcipants&

were&tested&for&interacGon&on&the&addiGve&scale&using&the& Interac$on'Contrast'Ra$o'(ICR)1:'

ICR'='ORboth&pesGcides&–&ORpesGcide&1&–&ORpesGcide&2+1&

ICR'>'0.5'indicates'super@addi$ve'joint'effects'

1&De&Roos&AJ,&Zahm&SH,&Cantor&KP&et&al.&Occup&Environ&Med.&2003;&60(9):E11.&&

Results''

• 342&MM&cases,&1506&controls&
• Response&rate:&58%&for&cases,&48%&for&controls&
• Compared&to&controls,&MM&cases:&

– Were&older&(64&vs.&54&years)& – Had&higher&use&of&proxy&respondents&(30&%&vs.&15%)&& – Had&a&higher&proporGon&of&ever&smokers&(74%&vs.&64%)&

&

Results'@'Carcinogenicity'

&

&

Note:&a&composite&carcinogenicity&score&was&created&using&assessments&from&the& IARC&Monographs,&US&Environmental&ProtecGon&Agency&(EPA)&Integrated&Risk& InformaGon&System&(IRIS),&and&the&US&EPA&Office&of&PesGcides&Program&(OPP)&

Number'of'pes$cides'used' Cases'N'(%)' Controls'N'(%)' ORadj'(95%'CI)' Possibly&carcinogenic&\&IARC&2B&or&higher& 0& 1& 2\4& 5&or&more& 248&(72.51)& 29&(8.48)& 46&(13.45)& 19&(5.56)& 1162&(77.16)& 107&(7.10)& 171&(11.35)& 66&(4.38)& 1.00& 1.51&(0.95,&2.39)& 1.24&(0.84,&1.82)& 1.45&(0.85,&2.47)& ptrend=0.07& Probably&carcinogenic&&\&IARC&2A&or&higher& 0& 1& 2& 3&or&more& 279&(81.58)& 37&(10.82)& 16&(4.68)& 10&(2.92)& 1317&(87.45)& 112&(7.44)& 54&(3.59)& 23&(1.53)& 1.00& 1.59'(1.03,'2.44)' 1.33&(0.76,&2.33)& 1.96'(0.96,'4.01)' ptrend=0.01'

Results'–'Chemical'Class'

&

&

Number'of'pes$cides'used' Cases'N'(%)' Controls'N'(%)' ORadj'(95%'CI)' Phenoxy&herbicides& 0& 1& 2\4& 5&or&more& 248&(72.51)& 29&(8.48)& 46&(13.45)& 19&(5.56)& 1188&(78.88)& 183&(12.15)& 86&(5.71)& 49&(3.25)& 1.00& 1.53'(1.08,'2.18)' 0.85&(0.47,&1.51)& 1.61&(0.85,&3.05)& ptrend=0.14& Organochlorines& 0& 1& 2& 3&or&more& 279&(81.58)& 37&(10.82)& 16&(4.68)& 10&(2.92)& 1317&(87.45)& 112&(7.44)& 54&(3.59)& 23&(1.53)& 1.00& 1.18&(0.80,&1.74)& 1.00&(0.55,&1.82)& 2.10'(1.03,'4.31)' ptrend=0.11& Carbamates& 0& 1&or&more& 315&(92.11)& 27&(7.89)& 1444&(95.88)& 62&(4.12)& 1.00& 2.08'(1.26,'3.42)'

.&

Results'–'Pes$cide'Combina$ons'

&

&

Pes$cide'Pair' Cases'N'(%)' Controls'N'(%)' ORadj'(95%'CI)' ICR' Glyphosate&and&2,4\D& Glyphosate&only& 2,4\D&only& Both& & 3&(0.88)& 51&(14.91)& 29&(8.48)& & 28&(1.86)& 188&(12.48)& 105&(6.97)& & 0.50&(0.15,&1.74)& 1.17&(0.82,&1.66)& 1.46&(0.92,&2.31)& 0.79' Chlordane&and&Mecoprop& Mecoprop&only& Chlordane&only& Both& & 13&(3.80)& 11&(3.22)& 14&(4.09)& & 43&(2.86)& 67&(4.45)& 38&(2.52)& & 1.44&(0.73,&2.81)& 0.78&(0.40,&1.53)& 2.00'(1.04,'3.86)' 0.79'

Note:&ICR>&0.5&indicates&that&the&joint&effect&exceeds&what&would&be&expected&

• n&the&addiGve&scale&

Conclusions'

• Focusing&on&occupaGonal&exposures&can&uncover&disGnct&risk&

factors&and&contribute&to&the&understanding&of&MM&eGology&&

• PosiGve&associaGons&observed&for&increasing&numbers&of&
• rganochlorine&pesGcides,&pesGcides&with&carcinogenic'

poten$al,&and&carbamate&pesGcides&suggest&that&these&may&be& risk&factors&for&MM&

• SynergisGc&effects&observed&for&certain&pesGcide&combinaGons&

suggest&that&addiGonal&research&is&needed&to&clarify&the&effects'

• f'pes$cide'mixtures''

Acknowledgments'

Cancer&Care&Ontario& OccupaGonal&Cancer&Research&Centre:&

• Paul'Demers,'Aaron'Blair,'Manisha'Pahwa,'Shelley'Harris'

Cross\Canada&Study&of&PesGcides&and&Health&invesGgators:&

• John'Spinelli,'John'McLaughlin,'Punam'Pahwa,'James'

Dosman'

&

For&more&informaGon:&& hSp://occupaGonalcancer.ca&& Linda.Kachuri@occupaGonalcancer.ca&&