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Research Articles

Inflammation-Related Gene Polymorphisms and Colorectal Adenoma

Marc J. Gunter, Federico Canzian, Stefano Landi, Stephen J. Chanock, Rashmi Sinha and Nathaniel Rothman
Marc J. Gunter
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Federico Canzian
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Stefano Landi
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Stephen J. Chanock
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Rashmi Sinha
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Nathaniel Rothman
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DOI: 10.1158/1055-9965.EPI-06-0042 Published June 2006
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Tables

  • Table 1.

    List of studied genes and SNPs

    GeneFunctionPolymorphismdbSNP no.Variant phenotype
    IL1BProinflammatory, primary initiator of inflammatory response−31C>Trs1143627C allele: increased expression (2)
    Ex5+14C>Trs1143634
    IL4Regulates antibody production, attenuates inflammatory response−584C>Trs2243250T allele: Increased transcriptional activity (29, 30)
    −1098G>Trs2243248
    IL5Hematopoietic growth factor, promotes growth and differentiation of eosinophils−745C>Trs2069812
    IL6Proinflammatory, initiator of inflammatory response, growth factor for cancer cells−174C>Grs1800795G allele: increased expression (31)
    IL8Proinflammatory chemokine, activates neutrophils−251A>Trs4073A allele: increased expression (22)
    IL10Anti-inflammatory, regulates T-cell and macrophage function−819C>Trs1800871In LD with −592 C>A SNP which is linked to reduced expression (27, 28)
    −1082A>Grs1800896A allele: reduced expression
    IL13Anti-inflammatory, suppresses IL1, IL6, and IL8 production−1069C>Trs1800925T allele: increased expression (32)
    IVS3−24T>Crs1295686
    LTAProinflammatory, stimulates prostaglandin synthesis, induces reactive oxygen species production in neutrophilsIVS1−82G>Crs746868
    IVS1+90G>Ars909253
    TNFProinflammatory, key immunomediator−308A>Grs1800629A allele: higher transcriptional activation (33, 34)
    PPARGAnti-inflammatory, tumor suppressor and promoter propertiesEx4−49C>G (Pro12Ala)rs1801282Ala allele: reduced ligand binding (35)
    PTGS2Converts arachidonic acid to prostaglandins, thereby promoting inflammatory response−765C>Grs20417C allele: reduced expression (36)
    (COX2)Ex3−8G>Crs5277
    IVS5−275G>Trs20432
    Ex10+837C>Trs5275
  • Table 2.

    Characteristics of the study population

    CharacteristicCases (n = 244)Controls (n = 231)P*
    Females (%)22.536.40.0009†
    Age (y)60 (55.5-74.5)57 (43-71)0.07
    Non-White (%)11.19.10.48†
    Body mass index (kg/m2)26.5 (21.9-31.2)25.8 (21.1-30.5)0.04
    Smoking status
        Current smoker (%)11.14.80.01†
        Regular smoker (y)26 (6-46)18 (0-36)0.0001
        Cigarettes per day20 (0.8-39.2)20 (0-40)0.012
    NSAID use‡ (%)51.665.40.002†
    Family history of colon cancer (%)16.811.90.13†
    • NOTE: All values are medians (interquartile range) unless otherwise indicated.

    • ↵* Ps derived from the Wilcoxon signed rank sum test unless otherwise indicated.

    • ↵† P derived from the χ2 test.

    • ↵‡ Denotes regular use of aspirin or other NSAIDs.

  • Table 3.

    Genotype distributions and genotypic risks for association with colorectal adenoma for cytokine and other inflammation-related genes

    GenotypeCases, n (%)Controls, n (%)OR* (95% CI)
    IL1B −31
        T/T74 (37.6)92 (48.2)1.0
        C/T99 (50.2)68 (35.6)1.8 (1.2-2.9)
        C/C24 (12.2)31 (16.2)0.9 (0.5-1.7)
        Ptrend = 0.01
    C-carrier123 (62.4)99 (49.8)1.5 (1.0-2.3)
    IL1B Ex5 +14
        C/C131 (59.0)129 (61.7)1.0
        C/T78 (35.1)66 (31.6)1.1 (0.7-1.7)
        T/T13 (5.9)14 (6.7)0.9 (0.4-2.0)
        Ptrend = 0.82
        T-carrier91 (41.0)80 (38.3)1.1 (0.7-1.6)
    IL4 −584
        T/T132 (68)114 (64.8)1.0
        C/T53 (27.3)53 (30.1)0.9 (0.5-1.4)
        C/C9 (4.6)9 (5.1)0.8 (0.3-2.6)
        Ptrend = 0.86
        C-carrier60 (31.9)62 (35.2)0.8 (0.5-1.4)
    IL4 −1098
        T/T177 (84.3)156 (82.1)1.0
        G/T33 (15.7)32 (16.8)0.9 (0.5-1.5)
        G/G0 (0)2 (1.1)
        Ptrend = 0.91
        G-carrier33 (15.7)34 (17.9)0.9 (0.5-1.5)
    IL5 −74
        C/C94 (44.8)82 (43.2)1.0
        C/T92 (43.8)85 (44.7)0.9 (0.6-1.5)
        T/T24 (11.4)23 (12.1)0.8 (0.4-1.8)
        Ptrend = 0.90
        T-carrier116 (55.2)108 (56.8)0.9 (0.6-1.4)
    IL6 −174
        G/G79 (38.7)83 (43.7)1.0
        C/G90 (44.1)81 (42.6)1.1 (0.7-1.8)
        C/C35 (17.2)26 (13.7)1.5 (0.8-2.9)
        Ptrend = 0.40
        C-carrier125 (61.3)107 (56.3)1.2 (0.8-1.9)
    IL8 −251
        T/T52 (25.4)65 (34.0)1.0
        A/T87 (42.4)94 (49.2)1.2 (0.7-1.9)
        A/A66 (32.2)32 (16.8)2.7 (1.5-4.9)
        Ptrend = 0.002
        A-carrier153 (74.6)126 (66.0)1.5 (1.0-2.4)
    IL10 −819
        C/C125 (56.3)117 (56.0)1.0
        C/T76 (34.2)79 (37.8)1.0 (0.6-1.5)
        T/T21 (9.5)13 (6.2)2.1 (0.9-4.8)
        Ptrend = 0.19
        T-carrier97 (43.7)92 (44.0)1.1 (0.7-1.6)
    IL10 −1082
        A/A61 (27.5)55 (26.6)1.0
        A/G114 (51.4)123 (59.4)0.8 (0.5-1.3)
        G/G47 (21.1)29 (14.0)1.3 (0.7-2.4)
        Ptrend = 0.17
        G-carrier161 (72.5)152 (73.4)0.9 (0.6-1.4)
    IL13 −1069
        C/C120 (61.5)102 (59.7)1.0
        C/T67 (34.4)58 (33.9)1.0 (0.6-1.6)
        T/T8 (4.1)11 (6.4)0.7 (0.2-1.8)
        Ptrend = 0.69
        T-carrier75 (38.5)69 (40.3)1.0 (0.6-1.5)
    IL13 IVS3 −24
        C/C128 (61.5)110 (57.0)1.0
        C/T70 (33.7)73 (37.8)0.8 (0.5-1.2)
        T/T10 (4.8)10 (5.2)0.8 (0.3-2.3)
        Ptrend = 0.55
        T-carrier80 (37.5)83 (43.0)0.8 (0.5-1.2)
    LTA IVS1 −82
        G/G85 (38.8)76 (37.1)1.0
        C/G107 (48.9)102 (49.8)1.0 (0.6-1.5)
        C/C27 (12.3)27 (13.1)0.9 (0.5-1.6)
        Ptrend = 0.91
        C-carrier134 (61.2)129 (62.9)1.0 (0.6-1.4)
    LTA IVS1+90
        A/A90 (39.8)88 (42.1)1.0
        A/G101 (44.7)92 (44.0)1.2 (0.8-1.8)
        G/G35 (15.5)29 (13.9)1.2 (0.7-2.2)
        Ptrend = 0.71
        G-carrier136 (60.2)114 (57.9)1.2 (0.8-1.7)
    TNF −308
        G/G146 (67.3)139 (68.8)1.0
        A/G59 (27.2)57 (28.2)1.0 (0.7-1.6)
        A/A12 (5.5)6 (3.0)1.9 (0.7-5.4)
        Ptrend = 0.46
        A-carrier71 (32.7)63 (31.2)1.1 (0.7-1.7)
    PPARG −Pro12Ala
        G/G153 (77.3)146 (79.4)1.0
        G/C41 (20.7)37 (20.1)1.1 (0.7-1.8)
        C/C4 (2.0)1 (0.5)3.2 (0.3-31.1)
        Ptrend = 0.56
        C-carrier45 (22.7)38 (21.5)1.2 (0.7-1.9)
    PTGS2 −765
        G/G151 (71.9)141 (71.9)1.0
        G/C54 (25.7)52 (26.5)0.9 (0.6-1.4)
        C/C5 (2.4)3 (1.5)1.3 (0.3-5.9)
        Ptrend = 0.85
        C-carrier59 (28.1)55 (28.0)0.9 (0.6-1.5)
    PTGS2 Ex3 −8
        G/G154 (73.3)142 (72.1)1.0
        G/C52 (24.8)51 (25.9)1.0 (0.6-1.6)
        C/C4 (1.9)4 (2.0)1.2 (0.3-5.1)
        Ptrend = 0.97
        C-carrier56 (26.7)55 (27.9)1.0 (0.6-1.6)
    PTGS2 IVS5 −275
        T/T149 (71.0)136 (69.0)1.0
        T/G54 (25.7)57 (28.9)0.8 (0.5-1.3)
        G/G7 (3.3)4 (2.1)1.4 (0.4-5.1)
        Ptrend = 0.53
        G-carrier61 (29.0)61 (31.0)0.9 (0.6-1.3)
    PTGS2 Ex10 +837
        C/C92 (43.8)77 (39.1)1.0
        T/C88 (41.9)102 (51.8)0.7 (0.5-1.1)
        T/T30 (14.3)18 (9.1)1.2 (0.6-2.4)
        Ptrend = 0.16
        T-carrier118 (56.2)120 (60.9)0.8 (0.5-1.2)
    • ↵* ORs adjusted for age, sex, and ethnicity.

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Cancer Epidemiology Biomarkers & Prevention: 15 (6)
June 2006
Volume 15, Issue 6
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Inflammation-Related Gene Polymorphisms and Colorectal Adenoma
Marc J. Gunter, Federico Canzian, Stefano Landi, Stephen J. Chanock, Rashmi Sinha and Nathaniel Rothman
Cancer Epidemiol Biomarkers Prev June 1 2006 (15) (6) 1126-1131; DOI: 10.1158/1055-9965.EPI-06-0042

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Inflammation-Related Gene Polymorphisms and Colorectal Adenoma
Marc J. Gunter, Federico Canzian, Stefano Landi, Stephen J. Chanock, Rashmi Sinha and Nathaniel Rothman
Cancer Epidemiol Biomarkers Prev June 1 2006 (15) (6) 1126-1131; DOI: 10.1158/1055-9965.EPI-06-0042
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