Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.
Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.
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DOI：
10.1371/journal.pone.0125273
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hudson T
中科院分区：
文献类型：
--
作者：
Cotterchio M;Lowcock E;Bider-Canfield Z;Lemire M;Greenwood C;Gallinger S;Hudson T
许多流行病学研究报告称，过敏等特应性疾病与降低胰腺癌风险有关。这种关系的原因尚不清楚。这是第一项全面评估特应性相关候选基因变异与胰腺癌风险之间关系的研究。一项基于人群的病例对照研究对2011-2012年期间诊断的胰腺癌病例进行了研究(通过安大略省癌症登记中心)，并使用随机数字拨号招募了对照，利用了179例病例和566名对照的DNA。在查阅了详尽的文献后，使用DBGaP胰腺癌基因数据库对180个候选基因中的SNPs进行了预筛选；保留了56个变态反应相关免疫基因中的147个SNPs并进行了基因分型。用Logistic回归估计每个变异体的年龄调整奇比(AOR)，并用假发现率调整Wald P值进行多次测试。随后，根据具有统计学意义的变量得出风险等位基因得分。14个候选基因(CSF2、DENND1B、DPP10、FLG、IL13、IL13RA2、LRP1B、NOD1、NPSR1、ORMDL3、RORA、STAT4、TLR6、TRA)中的18个SNP与胰腺癌风险显著相关。在调整多重比较后，两个LRP1B SNP仍然具有统计学意义；例如，LRP1B rs1449477(AA与CC：AOR=0.37，95%CI：0.22-0.62；p(调整后)=0.04)。此外，风险等位基因得分与显著降低胰腺癌风险相关(p=0.0007)。初步研究结果表明，某些与特应性疾病相关的变异可能与胰腺癌风险有关。需要进一步的研究来重复这一点，并阐明越来越多的流行病学证据表明过敏可能降低胰腺癌风险背后的生物学。
Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants. 18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007). Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1158/1055-9965.epi-13-0965
发表时间：
2014-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Cotterchio M;Lowcock E;Hudson TJ;Greenwood C;Gallinger S
通讯作者：
Gallinger S