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腾讯登录美称常服阿司匹林可降低结肠癌风险 对特定人群或无助
| 导读 | 日前刊登在国际杂志Journal of the American Medical Association上的一篇研究论文中，来自麻省总医院的研究人员通过研究表明，个体服用阿司匹林或其相关的非甾体抗炎药(NSAIDs)引发的结直肠癌风险的下降或许依赖于两种常见的单核苷酸多态性(Single Nucleotide Polymorph Sims，SNPs)的存在。 |
日前刊登在国际杂志Journal of the American Medical Association上的一篇研究论文中，来自麻省总医院的研究人员通过研究表明，个体服用阿司匹林或其相关的非甾体抗炎药(NSAIDs)引发的结直肠癌风险的下降或许依赖于两种常见的单核苷酸多态性(Single Nucleotide Polymorph Sims，SNPs)的存在。
此前研究中，研究者表明，阿司匹林及NSAIDs的有规律服用或许和个体患结直肠癌风险减小直接相关，相比正常人群患结直肠癌风险而言，这些个体患癌风险会降低30%；但在12号和15号染色体SNP位点上携带低频率等位基因的个体中这种患癌风险降低的效应却消失了，而这种突变或许最终会证明靶向服用阿司匹林及NSAIDs是有效的。
Andrew Chan教授指出，自从这些药物被认为具有严重副作用，尤其是引发胃肠道出血后，确定不会从这些药物中获益的人群将对于规范其治疗非常重要；而本文研究则表明，加入个体的遗传信息或许可以帮助研究者们制定决策，然而推荐进行遗传筛查来指导临床护理还为时过早，本文的研究还需要在其他人群中进行研究才可以证实。文章中，研究者依赖于在1976年至2011年间获取的8634名结直肠癌患者及8553名未受影响个体的研究信息进行分析，随后研究者进行了一项通过环境来分析基因的研究，其可以直接检测和估算个体机体的单核苷酸多态性，同时也进行了相关的结直肠癌诊断及个体阿司匹林的服用。
总的来讲，阿司匹林及NSAIDs的有规律的服用和人群中结直肠癌的流行率从38%下降至28%直接相关，而且12号染色体SNP rs2965667携带两个拷贝胸腺嘧啶等位基因的个体，如果有规律地服用阿司匹林及NSAIDs后会使得其患结直肠癌的风险比通常患癌风险要低。但对于携带罕见胸腺嘧啶-腺嘌呤或腺嘌呤-腺嘌呤基因型的个体而言，他们服用阿司匹林及NSAIDs后会增加患结直肠癌的风险。
研究者对结直肠癌患者进行分析后发现，在15号染色体的SNP rs16973225携带有胞嘧啶纯合子或单一拷贝的胞嘧啶-腺嘌呤的个体中并没有观察到个体服用阿司匹林及NSAIDs后引发的患癌风险下降。研究者表示，后期还需要进行更多研究来证实本文中所观察到的结果，后期还有待于观察是否其它突变会影响药物有规律服用引发的风险或效应。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：
JAMA doi:10.1001/jama.2015.1815
Hongmei Nan, MD, PhD1,2; Carolyn M. Hutter, MS, PhD3; Yi Lin, MS4; Eric J. Jacobs, PhD, MS5; Cornelia M. Ulrich, PhD4,6; Emily White, PhD4,7; John A. Baron, MD8; Sonja I. Berndt, PharmD, PhD9; Hermann Brenner, MD, MPH10,11; Katja Butterbach, PhD10; Bette J. Caan, DrPH12; Peter T. Campbell, PhD5; Christopher S. Carlson, PhD4; Graham Casey, PhD13; Jenny Chang-Claude, PhD14; Stephen J. Chanock, MD9; Michelle Cotterchio, PhD15; David Duggan, PhD16; Jane C. Figueiredo, PhD13; Charles S. Fuchs, MD, MPH17; Edward L. Giovannucci, MD18; Jian Gong, PhD4; Robert W. Haile, DrPH13; Tabitha A. Harrison, MPH4; Richard B. Hayes, DDS, PhD19; Michael Hoffmeister, PhD10; John L. Hopper, PhD20; Thomas J. Hudson, MD21,22; Mark A. Jenkins, PhD20; Shuo Jiao, PhD4; Noralane M. Lindor, MD23; Mathieu Lemire, PhD22; Loic Le Marchand, MD, PhD24; Polly A. Newcomb, PhD, MPH4; Shuji Ogino, MD, PhD17,25,26; Bethann M. Pflugeisen, PhD4; John D. Potter, MD, PhD4,27; Conghui Qu, PhD4; Stephanie A. Rosse, PhD4; Anja Rudolph, PhD14; Robert E. Schoen, MD, MPH28; Fredrick R. Schumacher, PhD13; Daniela Seminara, PhD, MPH3; Martha L. Slattery, PhD29; Stephen N. Thibodeau, PhD30,31; Fridtjof Thomas, PhD32; Mark Thornquist, PhD4; Greg S. Warnick4; Brent W. Zanke, MD, PhD, FRCPC33; W. James Gauderman, PhD13; Ulrike Peters, PhD, MPH4,7; Li Hsu, PhD4,34; Andrew T. Chan, MD, MPH18,35 ; for the CCFR and GECCO
Importance Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer.
Objective To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer.
Design, Setting, and Participants Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent.
Exposures Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors.
Main Outcomes and Measures Colorectal cancer.
Results Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10−28) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10−9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10−33) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10−9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10−30) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76).
Conclusions and Relevance In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.
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