Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 16, Issue 4, Pages 747-755Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-06-0667
Keywords
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Funding
- DIVISION OF CANCER CONTROL &POPULATION SCIENCE [N01PC067000] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [R01CA078762, R01CA078802, R01CA078682, R01CA078552] Funding Source: NIH RePORTER
- NCI NIH HHS [N01-PC-67000, CA078552, CA078682, CA078762, R01 CA078682-07, R01 CA078682, CA078802] Funding Source: Medline
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Interleukin-6 is a cytokine thought to be involved in inflammation, insulin, and estrogen-related pathways. We evaluate genetic variation in the IL6 gene with risk of breast cancer. We also evaluate breast cancer associations with aspirin and nonsteroidal anti-inflammatory drugs. A breast cancer case-control study (n = 1,527 non-Hispanic white cases, 1,601 non-Hispanic white controls, 798 Hispanic/ Native American cases, and. 924 Hispanic/Native American controls) was conducted among women living in the southwestern United Stales (4-Corner's Breast Cancer Study). Five IL6 single nucleotide polymorphisms (SNP) and IL6 haplotypes based on these SNPs were evaluated. Allele frequencies were significantly different between non-Hispanic white and Hispanic/Native American women. Among postmenopausal women not recently exposed to hormones, the AG/GG genotypes of rs1800797 (-596A > G) and the GC/CC genotypes of rs1800795 (-174G > C) significantly reduced risk of breast cancer among non-Hispanic white women [odds ratio (OR), 0.69; 95% confidence interval (95% CD, 0.48-1.00 and OR, 0.68; 95% Cl, 0.47-0.99, respectively] and Hispanic/Native American women (OR, 0.48; 95% Cl, 0.28-0.83 and OR, 0.44; 95% Cl, 0.26-0.99, respectively). Haplotypes of the five IL6 SNPs further defined these associations. Recent aspirin use significantly decreased risk of breast cancer among postmenopausal Hispanic/Native American women not recently exposed to hormones (OR, 0.56; 95% Cl, 0.33-0.96). Among non-Hispanic white, the inverse association with aspirin was not statistically significant. IL6 genotype and haplotype significantly modified the association between aspirin and breast cancer, with the greatest effect modification being among women not recently exposed to hormones [P interaction = 0.06 (for non-Hispanic white) and 0.04 (for Hispanic/Native American) and SNP rs1800796 or -572G > C]. These data suggest that IL6 is associated with breast cancer risk and modifies the association between estrogen and aspirin and breast cancer risk.
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