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Single Nucleotide Polymorphisms Associated With Colorectal Cancer Preventive Effect of Aspirin or NSAIDs in Persons of European Descent

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Key Points

  • Regular aspirin/NSAID use was associated with a 34% reduction in risk of colorectal cancer among persons with the rs2965667-TT genotype at chromosome 12 (96% of the population).
  • Regular use was associated with a 34% reduction in risk among persons with the rs16973225-AA genotype at chromosome 15 (91% of the population).

In a study reported in JAMA, Nan et al found that two single nucleotide polymorphisms (SNPs) were associated with a reduced risk of colorectal cancer with regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use by persons of European descent.

Study Details

The case-control study involved analysis of gene × environment interactions in data from five case-control and five cohort studies started between 1976 and 2003 in the United States, Canada, Australia, and Germany, including 8,634 colorectal cancer cases and 8,553 matched controls. All persons were of European descent.

Regular use of aspirin/NSAIDs, defined differently for the individual studies included in the analysis, was associated with a lower risk of colorectal cancer vs nonregular use (regular use prevalence = 28% among cases vs 38% among controls, odds ratio [OR] = 0.69, P = 6.2 × 10−28).

SNP at Chromosome 12

The SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin/NSAID use (P = 4.6 × 10−9 for interaction) in logistic regression analysis. Regular aspirin/NSAID use was associated with a lower risk of colorectal cancer in persons with the highly common (96% of the population) rs2965667-TT genotype (prevalence = 28% vs 38%, OR = 0.66, P = 7.7 × 10−33) but with an increased risk among those with TA or AA genotypes (4% of the population; prevalence = 35% vs 29%, OR = 1.89, P = .002).

SNP at Chromosome 15

The SNP rs16973225 at chromosome 15q25.2 near the IL16 gene also showed a genome-wide significant interaction with aspirin/NSAID use (P = 8.2 × 10−9 for interaction) on case-only interaction analysis. Regular use was associated with a lower risk of colorectal cancer among persons with the highly common (91% of the population) rs16973225-AA genotype (prevalence = 28% vs 38%, OR = 0.66, P = 1.9 x 10−30) but did not affect the risk among those with the AC or CC genotype (9% of the population; prevalence = 36% vs 39%, OR = 0.97, P = .76).

The investigators concluded: “In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with a 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.”

Li Hsu, PhD, of Fred Hutchinson Cancer Research Center, and Andrew T. Chan, MD, MPH, of Massachusetts General Hospital, are the corresponding authors of the JAMA article.

The study was supported by the National Cancer Institute, National Institutes of Health, and others. For full disclosures of the study authors, visit jama.jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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