, Volume 58, Issue 1, pp 1–8

The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement

  • Emilian Racila
  • Doina M. Racila
  • Justine M. Ritchie
  • Christiana Taylor
  • Christopher Dahle
  • George J. Weiner
Original Paper


Complement is one of primary defense mechanisms against intravascular microorganisms and could play a role in the immune response to malignancy and hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA associates with outcome in patients with breast carcinoma. Genotyping for C1qA[276A/G] was performed in 63 breast cancer subjects with localized tumor and compared with that in 38 breast cancer subjects with metastasis. Established risk factors for clinical outcome were considered and evaluated in multivariable analysis. Breast cancer subjects with heterozygous or homozygous C1qA[276G] genotype had a higher rate of metastasis than subjects with the homozygous C1qA[276A] genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1–4.1]. This association was stronger when only metastatic sites associated with hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR 3.5, 95% CI 1.4–5.6) and remained statistically significant after adjustment for the number of positive lymph nodes, estrogen receptor status, and progesterone receptor status. There was no statistical difference in the C1qA[276A/G] allelic distribution between all subjects with breast cancer and controls. These results suggest there could be an association of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites linked to hematogenous spread of disease. The C1qA polymorphism associated with decreased distant metastasis has also been correlated with an increased incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an altered immune response may play a role in the observed association.


Complement Single nucleotide polymorphism (SNP) Breast cancer Metastasis 


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Emilian Racila
    • 1
  • Doina M. Racila
    • 2
  • Justine M. Ritchie
    • 3
  • Christiana Taylor
    • 1
  • Christopher Dahle
    • 1
  • George J. Weiner
    • 1
    • 2
  1. 1.Holden Comprehensive Cancer Center at the University of Iowa, 5216MERFUniversity of IowaIowaUSA
  2. 2.Department of Internal MedicineUniversity of IowaIowaUSA
  3. 3.Department of BiostatisticsUniversity of IowaIowa CityUSA

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