Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women.
OBJECTIVE
Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown.


METHODS
In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1alpha gene (IL1A), -511 C/T polymorphism of the IL1beta promoter (IL1B promoter), a polymorphism of IL1beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing.


RESULTS
Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables.


CONCLUSIONS
Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.
Hefler
Lukas A
LA
Department of Obstetrics and Gynecology, Medical University of Vienna, Austria. lukas.hefler@meduniwien.ac.at
Grimm
Christoph
C
Lantzsch
Tilmann
T
Lampe
Dieter
D
Leodolter
Sepp
S
Koelbl
Heinz
H
Heinze
Georg
G
Reinthaller
Alexander
A
Tong-Cacsire
Dan
D
Tempfer
Clemens
C
Zeillinger
Robert
R
D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D007375:Interleukin-1; D015850:Interleukin-6