Functional single-nucleotide polymorphisms in the BRCA1 gene and risk of salivary gland carcinoma
ABSTRACT Polymorphic BRCA1 is a vital tumor suppressor gene within the DNA double-strand break repair pathways, but its association with salivary gland carcinoma (SGC) has yet to be investigated.
In a case-control study of 156 SGC patients and 511 controls, we used unconditional logistical regression analyses to investigate the association between SGC risk and seven common functional single-nucleotide polymorphisms (A1988G, A31875G, C33420T, A33921G, A34356G, T43893C and A55298G) in BRCA1.
T43893C TC/CC genotype was associated with a reduction of SGC risk (adjusted odds ratio=0.55, 95% CI: 0.38-0.80, Bonferroni-adjusted p=0.011), which was more pronounced in women, non-Hispanic whites, and individuals with a family history of cancer in first-degree relatives. The interaction between T43893C and family history of cancer was significant (p=0.009). The GATGGCG and AACAACA haplotypes, both of which carry the T43893C minor allele, were also associated with reduced SGC risk.
Our results suggest that polymorphic BRCA1, particularly T43893C polymorphism, may protect against SGC.
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ABSTRACT: BACKGROUND: The p14(ARF)/MDM2/p53 pathway plays an important role in modulation of DNA damage and oxidative stress responses. The aim of this study was to determine whether genetic variants in MDM2 and p14(ARF) are associated with risk of salivary gland carcinoma (SGC). METHODS: Four single nucleotide polymorphisms (SNPs) in MDM2 and p14(ARF) (MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440) were genotyped in 156 patients with SGC and 511 cancer-free controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: MDM2-rs2279744 was significantly associated with a moderately increased risk of SGC (OR, 1.5, 95% CI, 1.1-2.2). There was a trend toward significantly increased SGC risk with increasing number of risk genotypes of the four polymorphisms (P(trend) = 0.004). Individuals carrying 3-4 risk genotypes in MDM2 and p14(ARF) were at increased SGC risk (OR, 2.0, 95% CI, 1.1-2.7) compared with individuals carrying 0-2 risk genotypes. Moreover, the combined effect of risk genotypes of MDM2 and p14(ARF) was more pronounced among young subjects (≤45 years), female subjects, subjects with race/ethnicity other than non-Hispanic white, ever-smokers, and ever-drinkers. CONCLUSION: Our results support the involvement of SNPs of MDM2 and p14(ARF), either alone or more likely in combination, in susceptibility to SGC. Larger studies are needed to validate our findings.PLoS ONE 11/2012; 7(11):e49361. DOI:10.1371/journal.pone.0049361 · 3.53 Impact Factor