Single nucleotide polymorphism in the interleukin 12B gene is associated with risk for breast cancer development.
We analysed the association of a single nucleotide polymorphism (SNP) in the gene encoding the IL-12 subunit p40 (IL12B, rs3212227, A>C) with breast cancer. The SNPs allelic and genotypic frequencies were compared between patients (n = 191) and healthy (n = 194) women in a case-control study from Croatia. The major allele (A) was associated with susceptibility to breast cancer (P = 0.003; OR = 1.67; 95% CI: 1.17-2.38). Likewise, the minor allele (C) was significantly correlated with protection (P = 0.003; OR = 0.60; 95% CI: 0.42-0.86). At the genotype level, AA homozygosity was significantly associated with predisposition to disease (P = 0.013; OR = 1.68, 95% CI: 1.09-2.59), whereas the minor allele homozygosity (CC) was correlated with protection to disease (P = 0.020, OR = 0.28, 95% CI: 0.09-0.91). The heterozygous genotype showed no significant correlation with disease. The product of the IL12B gene (IL-12 p40) can either form a homodimeric cytokine or be part of two pro-inflammatory (IL-12 and IL-23) cytokines. It is presently unclear whether the major allele is associated with higher or lower protein levels of IL-12 p40 and IL-12 p70, which are critical in inflammation and adaptive immune responses. However, as the A allele is high producer of IL12B (p40) mRNA, these results might imply that higher levels of IL-12 p40 (either as homodimers or joined with one or both of the other two subunits) predispose to breast cancer.
Molecular Genetics Laboratory, Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
M H
MH
Kaarvatn
J
J
Vrbanec
A
A
Kulic
J
J
Knezevic
B
B
Petricevic
S
S
Balen
D
D
Vrbanec
Z
Z
Dembic
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D017523:Croatia; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40