Dataset Information

Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer.

ABSTRACT: Proinflammatory cytokines are associated with age-related diseases including arthritis and heart disease. IL6 and TNF also play key roles in estrogen modulation in older women. We explored whether variation in IL6 and TNF genes influenced the risk of breast cancer in samples that differed by age group: <44 years (228 cases and 271 controls), 45-64 years (426 cases and 396 controls), and 65+ years (228 cases and 239 controls). Samples were drawn from population-based case-control studies conducted in Seattle. Age-adjusted odds ratios (ORs) were calculated to evaluate the risk associated with variants in IL6, IL6R, TNF, and TNFRSF1A. There was a significantly increased risk of breast cancer associated with one or more C>T alleles at IL6 rs2069861 among subjects in the oldest age group (OR 1.8, 95% CI 1.1-2.9), but no overall increased risk of breast cancer associated with any IL6 or IL6R variants in the combined data. There were significantly elevated risks of breast cancer among women 45-64 years old associated with a UTR 5' flanking SNP LTA rs2009658 C>G allele (OR 1.5, 95% CI 1.1-1.9) and a nonsynonomous coding SNP TNFRSF1A rs767455 T>C allele (OR 1.3, 95% CI 1.1-1.6); these two variants were also elevated in the combined data (OR 1.3, 95% CI 1.1-1.5 and OR 1.2, 95% CI 1.1-1.4, respectively). This study supports a modest association between a variant in IL6 and breast cancer among older women and TNF-related variants and breast cancer among middle-aged women. Further evaluation of these genes in other studies is warranted.

SUBMITTER: Madeleine MM

PROVIDER: S-EPMC3164911 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer.

Madeleine Margaret M MM Johnson Lisa G LG Malkki Mari M Resler Alexa J AJ Petersdorf Effie W EW McKnight Barbara B Malone Kathleen E KE

Breast cancer research and treatment 20110427 3

Proinflammatory cytokines are associated with age-related diseases including arthritis and heart disease. IL6 and TNF also play key roles in estrogen modulation in older women. We explored whether variation in IL6 and TNF genes influenced the risk of breast cancer in samples that differed by age group: <44 years (228 cases and 271 controls), 45-64 years (426 cases and 396 controls), and 65+ years (228 cases and 239 controls). Samples were drawn from population-based case-control studies conducte ...[more]

PMID: 21523452

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Project description:BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with very preterm birth. The major risk factors include lung inflammation and lung immaturity. In addition, genetic factors play an important role in susceptibility to moderate-to-severe BPD. In this study, the aim was to investigate whether common polymorphisms of specific genes that are involved in inflammation or differentiation of the lung have influence on BPD susceptibility. METHODS: Genes encoding interleukin-6 (IL6) and its receptors (IL6R and IL6ST), IL-10 (IL10), tumor necrosis factor (TNF), and glucocorticoid receptor (NR3C1) were assessed for associations with moderate-to-severe BPD susceptibility. Five IL6, nine IL6R, four IL6ST, one IL10, two TNF, and 23 NR3C1 single nucleotide polymorphisms (SNPs) were analyzed in very preterm infants born in northern Finland (56 cases and 197 controls) and Canada (58 cases and 68 controls). IL-6, TNF and gp130 contents in umbilical cord blood, collected from very preterm infants, were studied for associations with the polymorphisms. Epistasis (i.e., interactions between SNPs in BPD susceptibility) was also examined. SNPs showing suggestive associations were analyzed in additional replication populations from Finland (39 cases and 188 controls) and Hungary (29 cases and 40 controls). RESULTS: None of the studied SNPs were associated with BPD nor were the IL6, TNF or IL6ST SNPs associated with cord blood IL-6, TNF and gp130, respectively. However, epistasis analysis suggested that SNPs in IL6ST and IL10 were associated interactively with risk of BPD in the northern Finnish population; however, this finding did not remain significant after correction for multiple testing and the finding was not replicated in the other populations. CONCLUSIONS: We conclude that the analyzed SNPs within IL6, IL6R, IL6ST, IL10, TNF, and NR3C1 were not associated with BPD. Furthermore, there was no evidence that the studied SNPs directly contribute to the cord blood protein contents.

Project description:BACKGROUND: The interaction of tumor necrosis factor-? (TNF-?) with its receptors: TNFRSF1A and TNFRSF1B is critical for the promotion of tumor growth, invasion and metastasis. To better understand the roles of single nucleotide polymorphisms (SNPs) in the TNF-?, TNFRSF1A and TNFRSF1B genes in the development of breast cancer, we explored the associations between SNPs in these three genes and breast cancer susceptibility in northeast Chinese Han women. METHODOLOGY/PRINCIPAL FINDINGS: This case-control study was conducted among 1016 breast cancer patients and 806 age-matched healthy controls. Seven SNPs in the TNF-? (rs1800629, rs361525), TNFRSF1A (rs767455, rs4149577 and rs1800693) and TNFRSF1B (rs1061622 and rs1061624) genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In TNFRSF1B, the rs1061622 GT genotype and the G allele conferred a reduced susceptibility to breast cancer (P?=?0.000662, OR?=?0.706, 95% CI: 0.578-0.863; P?=?0.002, OR?=?0.769, 95% CI; 0.654-0.905, respectively). Moreover, the AG genotype, the AA genotype and the A allele in rs1061624 conferred an increased risk of breast cancer (P?=?0.007, OR?=?1.470, 95% CI:1.112-1.943; P?=?0.00109, OR?=?1.405 95% CI:1.145-1.724; P?=?0.001, OR?=?1.248 95% CI:1.092-1.426, respectively). These two SNPs also had associations with breast cancer risk under the dominant model. In haplotype analysis, the CTA (rs767455 C-rs4149577 T-rs1800693 A) haplotype in TNFRSF1A and the TA (rs1061622 T-rs1061624 A) haplotype in TNFRSF1B had higher frequencies in breast cancer patients (P?=?0.00324; P?=?0.000370, respectively), but the frequency of GG (rs1061622 G-rs1061624 G) haplotype in TNFRSF1B was lower in breast cancer patients (P?=?0.000251). The associations of the three haplotypes remained significant after correcting for multiple testing. In addition, significant associations were also observed between TNFRSF1A polymorphisms and lymph node metastasis, P53, estrogen receptor (ER) and progesterone receptor (PR) statuses. CONCLUSIONS: Our results suggest that rs1061622 and rs1061624 in TNFRSF1B may affect breast cancer risk, and SNPs in TNFRSF1A are associated with the clinical features of breast cancer.

Dataset Information

Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer.

Publications

Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer.

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