凋亡相关单核苷酸多态性与女性非小细胞肺癌风险

Apoptosis-Related Single Nucleotide Polymorphisms and the Risk of Non-Small Cell Lung Cancer in Women.

作者信息

Pathak Anand, Wenzlaff Angela S, Hyland Paula L, Cote Michele L, Keele Greg R, Land Susan, Boulton Matthew L, Schwartz Ann G

机构信息

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850.

Population Studies and Disparities Research Program, Karmanos Cancer Institute, Wayne State University, 4100 John R., Mail Code: MM04EP, Detroit, MI 48201.

出版信息

J Cancer Ther Res. 2014;3(1). doi: 10.7243/2049-7962-3-1.

BACKGROUND

Germline apoptosis-related single nucleotide polymorphisms (SNPs) have been shown to contribute to the risk of developing non-small cell lung cancer (NSCLC). However, very few studies have looked specifically at apoptosis-related SNPs in a racially-stratified analysis of white and African-American women.

METHODS

We examined the risk of developing NSCLC associated with 98 germline SNPs in 32 apoptosis-related genes among women in a population-based case-control study from the Detroit metropolitan area. We examined 453 cases of NSCLC and 478 control subjects. We used an unconditional logistic regression with a dominant model, stratified by race, and adjusted for age, pack-years smoked, ever/never smoking status, family history of lung cancer, history of COPD, BMI and education.

RESULTS

Our logistic regression identified 3 significant apoptosis-related SNPs in whites ( rs1007573; rs3765459, and rs1535045), and 7 significant SNPs ( rs1801516; rs513349; rs1800629; rs6790167; rs7613791, rs35592567 and rs3856775 in African-Americans. In a downstream analysis, these SNPs were further prioritized utilizing the False Positive Report Percentage (FPRP) methodology and backwards elimination. In whites, rs1007573), rs3765459) and (rs1535045) were all found to be significant by FPRP. In African-Americans, SNPs rs6790167 and rs7613791 were found to have a significant FPRP. In parallel, a backward elimination procedure was used on the 3 significant SNPs in whites and 7 significant SNPs in African-Americans. This procedure identified rs1007573 (OR=1.86, 95% CI: 1.17-2.95) and rs1535045 (OR=0.58, 95% CI: 0.40-0.84) as significant independent predictors of risk among whites, and rs1801516 (OR=24.15, 95% CI: 3.50-166.55), rs1800629 (OR= 0.42, 95% CI: 0.18-0.99) and rs6790167 (OR: 2.85, 95% CI: 1.33-6.09) as significant, independent predictors in African-Americans.

CONCLUSION

In whites, only SNPs rs1007573 and rs1535045 were significant by both FPRP and backwards elimination, while in African-Americans, only rs6790167 was significant by both methodologies. Thus, we have identified three promising variants associated with increased risk of NSCLC that warrant additional investigation in future studies.

背景

种系凋亡相关单核苷酸多态性（SNP）已被证明与非小细胞肺癌（NSCLC）的发病风险有关。然而，很少有研究专门针对白人和非裔美国女性进行种族分层分析的凋亡相关SNP。

方法

在一项基于底特律大都市区人群的病例对照研究中，我们检测了32个凋亡相关基因中98个种系SNP与女性患NSCLC风险的关联。我们研究了453例NSCLC病例和478例对照受试者。我们采用优势模型的无条件逻辑回归，按种族分层，并对年龄、吸烟包年数、曾经/从未吸烟状态、肺癌家族史、慢性阻塞性肺疾病（COPD）史、体重指数（BMI）和教育程度进行了调整。

结果

我们的逻辑回归在白人中确定了3个与凋亡相关的显著SNP（rs1007573、rs3765459和rs1535045），在非裔美国人中确定了7个显著SNP（rs1801516、rs513349、rs1800629、rs6790167、rs7613791、rs35592567和rs3856775）。在下游分析中，利用假阳性报告率（FPRP）方法和向后剔除法对这些SNP进行了进一步排序。在白人中，rs1007573、rs3765459和rs1535045经FPRP分析均被发现具有显著性。在非裔美国人中，SNP rs6790167和rs7613791经FPRP分析具有显著性。同时，对白人中的3个显著SNP和非裔美国人中的7个显著SNP采用向后剔除法。该方法确定rs1007573（比值比[OR]=1.86，95%置信区间[CI]：1.17 - 2.95）和rs1535045（OR=0.58，95% CI：0.40 - 0.84）是白人中显著的独立风险预测因子；rs1801516（OR=24.15，95% CI：3.5-1）。

结论

在白人中，只有SNP rs1007573和rs1535045经FPRP和向后剔除法分析均具有显著性，而在非裔美国人中只有rs6790167经两种方法分析均具有显著性。因此，我们确定了三个与NSCLC风险增加相关的有前景的变异体，值得在未来研究中进一步研究。 66.55）、rs1800629（OR=0.42，95% CI：0.18 - 0.99）和rs6790167（OR：2.）。