Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7435, USA.
Environ Health Perspect. 2010 Apr;118(4):511-8. doi: 10.1289/ehp.0901233. Epub 2009 Nov 18.
Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology.
We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number.
We examined this possibility in a population-based case-control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing.
We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH-DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation-negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11-2.15] but not p53 mutation-positive (OR = 0.77; 95% CI, 0.43-1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C-->A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects.
These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation.
先前的研究表明，多环芳烃（PAHs）可能与乳腺癌有关。然而，PAHs 对人类乳房的致癌性尚不清楚。某些致癌物质可能与 p53 肿瘤抑制基因的特定突变模式有关，从而提供有关疾病病因的信息。
我们假设 PAH 相关暴露与乳腺癌的关联会因肿瘤 p53 突变状态、效应、类型和数量而异。
我们使用多项逻辑回归在一项基于人群的病例对照研究中检验了这种可能性。如前所述，使用 Surveyor 核酸酶在 859 个肿瘤中鉴定了 151 个 p53 突变，并通过测序进行了验证。
我们发现，与未发生 p53 突变的参与者相比，发生 p53 突变的参与者不太可能接触到 PAHs（通过对 859 例病例和 1556 例对照进行吸烟状况评估，对 822 例病例和 1475 例对照进行烤/熏肉摄入量评估，对 487 例病例和 941 例对照进行外周血单核细胞中 PAH-DNA 加合物评估）。例如，主动和被动吸烟与 p53 突变阴性（比值比 [OR] = 1.55；95%置信区间 [CI]，1.11-2.15）相关，但与 p53 突变阳性（OR = 0.77；95% CI，0.43-1.38）癌症（OR 比值 = 0.50，p < 0.05）无关。然而，移码突变、突变数量、CpG 位点的 G:C-->A:T 转换以及插入/缺失在暴露组中始终升高。
这些发现表明，PAHs 可能与特定的乳腺癌 p53 突变亚组相关，而不是与总体 p53 突变相关，并且可能通过 p53 突变以外的机制与乳腺癌相关。
