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

doi:10.1007/s00251-005-0077-y

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

Journal article

Peer reviewed

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 and George J Weiner

Immunogenetics (New York), Vol.58(1), pp.1-8

02/2006

DOI: 10.1007/s00251-005-0077-y

PMID: 16465510

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Abstract

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.

Genetic Predisposition to Disease

Humans

Middle Aged

Bone Neoplasms - secondary

Complement C1q - genetics

Receptors, Progesterone - metabolism

Neoplasm Metastasis - genetics

Brain Neoplasms - secondary

Time Factors

Breast Neoplasms - pathology

Lymphatic Metastasis - genetics

Aged, 80 and over

Breast Neoplasms - blood

Adult

Estrogen Receptor alpha - metabolism

Female

Aged

Polymorphism, Single Nucleotide

Carcinoma - pathology

Liver Neoplasms - secondary

Details

Title: Subtitle: The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement
Creators: Emilian Racila - Holden Comprehensive Cancer Center at the University of Iowa, 5216MERF, University of Iowa, Iowa, IA 52242, USA. emil-racila@uiowa.edu
Doina M Racila
Justine M Ritchie
Christiana Taylor
Christopher Dahle
George J Weiner
Resource Type: Journal article
Publication Details: Immunogenetics (New York), Vol.58(1), pp.1-8
DOI: 10.1007/s00251-005-0077-y
PMID: 16465510
ISSN: 0093-7711
eISSN: 1432-1211
Grant note: R21-CA90822 / NCI NIH HHS
Language: English
Date published: 02/2006
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
Record Identifier: 9984094550302771

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