Innate immunity gene polymorphisms and the risk of colorectal neoplasia

Cindy M. Chang; Victoria M. Chia; Marc J. Gunter; Krista A. Zanetti; Bríd M. Ryan; Julie E. Goodman; Curtis C. Harris; Joel Weissfeld; Wen Yi Huang; Stephen Chanock; Meredith Yeager; Richard B. Hayes; Sonja I. Berndt

doi:10.1093/carcin/bgt228

Innate immunity gene polymorphisms and the risk of colorectal neoplasia

Cindy M. Chang, Victoria M. Chia, Marc J. Gunter, Krista A. Zanetti, Bríd M. Ryan, Julie E. Goodman, Curtis C. Harris, Joel Weissfeld, Wen Yi Huang, Stephen Chanock, Meredith Yeager, Richard B. Hayes, Sonja I. Berndt

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (OR_{per T allele} = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10^-5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (OR_{per T allele} = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10^-9) than for adenoma (OR_{per T allele} = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (OR_{per T allele} = 0.5, 95% CI: 0.37-0.69 and OR_{per T allele} = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammationrelated genes may be related to the risk of colorectal neoplasia.

Original language	English (US)
Pages (from-to)	2512-2520
Number of pages	9
Journal	Carcinogenesis
Volume	34
Issue number	11
DOIs	https://doi.org/10.1093/carcin/bgt228
State	Published - Nov 2013
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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10.1093/carcin/bgt228

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@article{d56cf2820b7749ed81697720d6818440,

title = "Innate immunity gene polymorphisms and the risk of colorectal neoplasia",

abstract = "Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10-5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10-9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37-0.69 and ORper T allele = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammationrelated genes may be related to the risk of colorectal neoplasia.",

author = "Chang, {Cindy M.} and Chia, {Victoria M.} and Gunter, {Marc J.} and Zanetti, {Krista A.} and Ryan, {Br{\'i}d M.} and Goodman, {Julie E.} and Harris, {Curtis C.} and Joel Weissfeld and Huang, {Wen Yi} and Stephen Chanock and Meredith Yeager and Hayes, {Richard B.} and Berndt, {Sonja I.}",

note = "Funding Information: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and the Center for Cancer Research at the National Cancer Institute, National Institutes of Health; National Institutes of Health (U01 CA137088, R01 CA059045) to The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Funding for participating studies from GECCO follows: ARCTIC: National Institutes of Health (U01 CA074783); a GL2 grant from the Canadian Institutes of Health Research; and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Fran{\c c}aises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne G{\'e}n{\'e}tique and the Ligue R{\'e}gionale Contre le Cancer (LRCC). COLO2&3: National Institutes of Health (R01 CA60987). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1) and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). VITAL: National Institutes of Health (K05 CA154337). WHI: National Institutes of Health, NHLBI and HHS (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C).",

year = "2013",

month = nov,

doi = "10.1093/carcin/bgt228",

language = "English (US)",

volume = "34",

pages = "2512--2520",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "11",

}

TY - JOUR

T1 - Innate immunity gene polymorphisms and the risk of colorectal neoplasia

AU - Chang, Cindy M.

AU - Chia, Victoria M.

AU - Gunter, Marc J.

AU - Zanetti, Krista A.

AU - Ryan, Bríd M.

AU - Goodman, Julie E.

AU - Harris, Curtis C.

AU - Weissfeld, Joel

AU - Huang, Wen Yi

AU - Chanock, Stephen

AU - Yeager, Meredith

AU - Hayes, Richard B.

AU - Berndt, Sonja I.

N1 - Funding Information: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and the Center for Cancer Research at the National Cancer Institute, National Institutes of Health; National Institutes of Health (U01 CA137088, R01 CA059045) to The Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Funding for participating studies from GECCO follows: ARCTIC: National Institutes of Health (U01 CA074783); a GL2 grant from the Canadian Institutes of Health Research; and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC). COLO2&3: National Institutes of Health (R01 CA60987). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1) and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). VITAL: National Institutes of Health (K05 CA154337). WHI: National Institutes of Health, NHLBI and HHS (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C).

PY - 2013/11

Y1 - 2013/11

N2 - Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10-5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10-9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37-0.69 and ORper T allele = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammationrelated genes may be related to the risk of colorectal neoplasia.

AB - Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10-5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10-9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37-0.69 and ORper T allele = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammationrelated genes may be related to the risk of colorectal neoplasia.

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U2 - 10.1093/carcin/bgt228

DO - 10.1093/carcin/bgt228

M3 - Article

C2 - 23803696

AN - SCOPUS:84887007144

SN - 0143-3334

VL - 34

SP - 2512

EP - 2520

JO - Carcinogenesis

JF - Carcinogenesis

IS - 11

ER -

Innate immunity gene polymorphisms and the risk of colorectal neoplasia

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