IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry.
Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31-3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk.
Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia.|Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
María Carolina
MC
Sanabria-Salas
Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia.
Gustavo
G
Hernández-Suárez
Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
Adriana
A
Umaña-Pérez
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Konrad
K
Rawlik
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.|MRC-Human Genetics Unit, University of Edinburgh, UK.
Albert
A
Tenesa
Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia.|Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
Martha Lucía
ML
Serrano-López
Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
Myriam
M
Sánchez de Gómez
Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia.
Martha Patricia
MP
Rojas
Escuela de Salud Pública, Universidad del Valle, Cali, Colombia.
Luis Eduardo
LE
Bravo
Servicio de Gastroenterología, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia.
Rosario
R
Albis
Fundación Oftalmológica de Santander, Bucaramanga, Colombia.
José Luis
JL
Plata
Ochsner Clinic Foundation, New Orleans, LA, US.
Heather
H
Green
Ochsner Clinic Foundation, New Orleans, LA, US.
Theodor
T
Borgovan
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US.
Li
L
Li
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US.
Sumana
S
Majumdar
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US.
Jone
J
Garai
Department of Pathology &Cancer Center, Howard University College of Medicine, Washington, D.C., US.
Edward
E
Lee
Department of Pathology &Cancer Center, Howard University College of Medicine, Washington, D.C., US.
Hassan
H
Ashktorab
Department of Pathology &Cancer Center, Howard University College of Medicine, Washington, D.C., US.
Hassan
H
Brim
Ochsner Clinic Foundation, New Orleans, LA, US.
Li
L
Li
Ochsner Clinic Foundation, New Orleans, LA, US.
David
D
Margolin
Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, US.
Laura
L
Fejerman
Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US.|Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA, US.
Jovanny
J
Zabaleta
D000328:Adult; D000368:Aged; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003105:Colombia; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D001741:Black or African American
C508585:IL1B protein, human; D053583:Interleukin-1beta