Genetic variants affect the relationship between the risk of colorectal cancer and the use of Aspirin
Members of the Colon Cancer Family Registry (CCFR) and Genetics and Epidemiology projects of the Colorectal Cancer Consortium (GECCO) collected genetic and other data from more than 8,600 cases of colorectal cancer and 8,500 controls enrolled through studies in the USA, Canada, Australia, and Germany more than approximately three decades.
As shown in the past, the team determined that the regular use of aspirin or other NSAIDs corresponded to the risk of decreased colorectal cancer – down by about 30 percent compared to the risk of colorectal cancer in the general population.
But the protective effect vanished in individuals carrying low frequency alleles at the SNP sites on chromosome 12 and chromosome 15, suggesting that such variants may eventually prove useful in guiding the use of aspirin / NSAIDs.
“Because these medications are known to have serious side effects – especially gastrointestinal bleeding – determining whether certain groups of the population may not benefit is important for our ability to adapt recommendations for individual patients”
“This study suggests that the addition of information on a genetic profile could help in making that decision.”
“However, it is premature to recommend genetic screening to guide clinical care, since our results must be validated in other populations.”
The investigators relied on information from 8,634 individuals with colorectal cancer and 8,553 unaffected controls who had been included in the sample for the case-control study of the CCFR through nine case-control or cohort studies conducted by the GECCO between 1976 and 2011.
He then performs a gene-environment analysis that directly considers genotype and imputed SNPs of individuals, along with diagnoses of colorectal cancer and regular use of aspirin, to other NSAIDs, or both.
In general, the team found that aspirin and / or NSAID use regularly was associated with a prevalence of 28 percent of colorectal cancer – below the prevalence of 38 percent is described in the general population. However, the analysis highlights cases in which the drugs do not seem to confer a benefit.
For example, the regular use of aspirin / NSAIDs was linked to lower than normal rates of colorectal cancer in individuals with two copies of the thymine allele on chromosomes 12 rs2965667 SNP. But for those who have the rarer thymine-adenine or adenine-adenine genotypes, the risk of colorectal cancer appeared somewhat higher after regular use of aspirin / NSAIDs.
Similarly, in an analysis that specifically focused on cases of colorectal cancer, the researchers did not see the aspirin / dip associated with NSAIDs in the risk of colorectal cancer among individuals who were homozygous for the cytosine or had a copy of the cytosine and one of adenine on chromosome 15 rs16973225 SNP.
In contrast, individuals with the genotype-adenine adenine more common in rs16973225 seemed to get some benefit risk of colorectal cancer from the drugs.
The study authors cautioned that more research is needed to verify the results in individuals from other populations. In addition, it remains to be seen whether the responses of other impact or risk variants associated with the regular use of the drugs.
“An equally important question to be investigated is whether there are genetic influences on the likelihood that someone may be harmed by aspirin and NSAIDs.”