Pinheiro Simone P, Gates Margaret A, De Vivo Immaculata, Rosner Bernard A, Tworoger Shelley S, Titus-Ernstoff Linda, Hankinson Susan E, Cramer Daniel W
Int J Mol Epidemiol Genet. 2010 Sep 3;1(4):320-31.
Inflammation and non-steroidal anti-inflammatory agents (NSAIDs) may play important role in ovarian cancer. However, epidemiologic data are inconsistent, possibly reflecting inter-individual genetic differences affecting the metabolism of NSAIDs. We examined whether common polymorphisms affecting the metabolism of NSAIDs modify the association between NSAIDs and ovarian cancer risk. We genotyped 1,353 DNA samples from women who developed ovarian cancer and 1,823 samples from matched controls participating in the New England Case-Control study and the Nurses' Health Studies. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with regular use of NSAIDs and with relevant polymorphisms on ovarian cancer risk. Multivariable unconditional logistic regression estimated the association of NSAID use across stratum of each genotype. Regular use of NSAIDs was not associated with ovarian cancer risk. Multivariable OR (95% CI) associated with use NSAIDs was 0.85 (95% CI: 0.71-1.02). Associations between NSAID use and ovarian cancer risk did not differ significantly across strata of genotypes. None of the studied polymorphisms was associated with ovarian cancer risk. The multivariable ORs (95% CI) associated with CYP2C9 and UGT1A6 variant genotypes were 0.99 (0.90-1.08) and 0.93 (0.82-1.05), respectively. The multivariable ORs (95% CI) associated with PPAR-γ, COX-2 -765G>C, and COX-2 Ex10+837T>C polymorphisms were 1.02 (0.87-1.20), 0.87 (0.75-1.00), and 0.97 (0.87-1.09), respectively. In this relatively large study, we found no convincing evidence supporting an association between NSAIDs use and ovarian cancer risk. Furthermore, data did not suggest interaction between selected polymorphisms and use of NSAIDs in relation to ovarian cancer risk.
炎症和非甾体抗炎药（NSAIDs）可能在卵巢癌中发挥重要作用。然而，流行病学数据并不一致，这可能反映了影响NSAIDs代谢的个体间遗传差异。我们研究了影响NSAIDs代谢的常见多态性是否会改变NSAIDs与卵巢癌风险之间的关联。我们对参与新英格兰病例对照研究和护士健康研究的1353例卵巢癌女性的DNA样本以及1823例匹配对照的样本进行了基因分型。条件逻辑回归估计了与定期使用NSAIDs以及与卵巢癌风险相关的多态性相关的优势比（OR）和95%置信区间（CI）。多变量无条件逻辑回归估计了每种基因型分层中NSAIDs使用的关联。定期使用NSAIDs与卵巢癌风险无关。与使用NSAIDs相关的多变量OR（95%CI）为0.85（95%CI：0.71 - 1.02）。NSAIDs使用与卵巢癌风险之间的关联在各基因型分层中无显著差异。所研究的多态性均与卵巢癌风险无关。与CYP2C9和UGT1A6变异基因型相关的多变量OR（95%CI）分别为0.99（0.90 - 1.08）和0.93（0.82 - 1.05）。与PPAR - γ、COX - 2 - 765G>C和COX - 2 Ex10 + 837T>C多态性相关的多变量OR（95%CI）分别为1.02（0.87 - 1.20）、0.87（0.75 - 1.00）和0.97（0.87 - 1.09）。在这项相对较大的研究中，我们没有发现支持NSAIDs使用与卵巢癌风险之间存在关联的令人信服的证据。此外，数据并未表明所选多态性与NSAIDs使用在卵巢癌风险方面存在相互作用。
