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. 2006 Jul 14:6:188.
doi: 10.1186/1471-2407-6-188.

Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

S P Balasubramanian  1 , I A F Azmy, S E Higham, A G Wilson, S S Cross, A Cox, N J Brown, M W Reed
Affiliations

Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

S P Balasubramanian et al. BMC Cancer. .

Abstract

Background: Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity.

Methods: Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer.

Results: None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised.

Conclusion: Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.

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Figures

Figure 1
Figure 1
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL1A +4845 polymorphism. Log Rank test statistic = 1.52; df = 2; p = 0.47 (n = 482).
Figure 2
Figure 2
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL1B -511 polymorphism. Log Rank test statistic = 5.07; df = 2; p = 0.08 (n = 484).
Figure 3
Figure 3
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL1B +3954 polymorphism. Log Rank test statistic = 2.71; df = 2; p = 0.26 (n = 479).
Figure 4
Figure 4
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL1RN +2018 polymorphism. Log Rank test statistic = 4.32; df = 2; p = 0.12 (n = 481).
Figure 5
Figure 5
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL4R +1902 polymorphism. Log Rank test statistic = 2.07; df = 2; p = 0.35 (n = 528).
Figure 6
Figure 6
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL6 -174 polymorphism. Log Rank test statistic = 0.16; df = 2; p = 0.92 (n = 333).
Figure 7
Figure 7
shows the time to death or metastases in invasive breast cancer for the genotypes of the IL10 -1082 polymorphism. Log Rank test statistic = 1.34; df = 2; p = 0.51 (n = 332).
Figure 8
Figure 8
shows the linkage disequilibrium plot (obtained using Haploview) showing pairwise D' values (in percentage) between the four polymorphisms on chromosome 2q13. The markers 1, 2, 3 and 4 are IL1A +4845G>T, IL1B +3954C>T, IL1B -511 C>T and IL1RN +2018T>C respectively.
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