Aspirin in the 21st century
Why doesn’t aspirin protect everyone from colorectal cancer?
Dr Hongmei Nan – Indiana University–Purdue University Indianapolis, Indiana, USA
I received the Junior Investigator Award from the International Aspirin Foundation. As you know, aspirin use can prevent colorectal cancer risk but it does not work for everyone. So probably there are some genetic markers that can define people who may or may not get the exact benefit by aspirin use. So my research has been focussed on identifying those genetic markers that can define population groups who can get the benefit from aspirin use. We did this kind of research using the Gene Environment Interaction Study for Colorectal Cancer and we examined around more than 2.7 million SNPs, that is the single nucleotide polymorphism, in genetic environments across the whole human genome with the interaction for aspirin use and other non-steroidal anti-inflammatory use for colorectal cancer. Very interestingly, we found a genetic variant in a small group of the population, 9% of the population, who have a genetic variant on chromosome 15 that will have no benefit by use of aspirin for colorectal cancer.
What’s more is that a small number of the population, like 4% of participants, who have the rare chromosome 12, if this small population group use aspirin it can increase the risk of colorectal cancer. So, in other words, the aspirin may have even adverse effects for colorectal cancer prevention in this small group of population. So this is our major finding.
Can you outline the population of patients that was studied in the research?
In my genome wide gene environment interaction study, we included more than 8.500 colorectal cancer case controlled pairs that have been on-going more than four decades in four different countries. So this is the big population group in colorectal cancer from the colorectal cancer consortium.
What is the clinical relevance of your findings and what needs to be done next?
Of course, by genotyping of this one single nucleotide polymorphism that we identified in our study is unlikely sufficient to do the clinical care for colorectal cancer. But the advantage of our study is that if our findings are validated in additional studies it may promote the prevention of colorectal cancer. And based on our study we can further develop the additional investigations and we can identify more genes related to aspirin and colorectal cancer prevention. So I think our study can motivate the future investigations and in the future the clinicians may use a panel of genes, not like only one gene, a panel of genes to better decide their recommendation for individual patients. So this study can contribute to the precedent, the precise medicine strategy.
What further research plans do you have?
We have several plans about that. So first, because we just identified a single polymorphism related to aspirin and colorectal cancer but we do not know the exact underlying mechanism of this SNP for the colorectal cancer pathway. So probably we can do a further functional study to document if this SNP is related to or may alter some specific genes that are further related to aspirin and colorectal cancer. On the other hand, now with a number of new technologies that enable analysis, the whole genome analysis, so we can further conduct some individual analyses. For example, we can incorporate the data and the whole genome gene expression data and identify some biological pathways that are related to colorectal cancer and further examine the interaction between this kind of identified pathway and environment, like aspirin use on risk of colorectal cancer. So one of the benefits of this kind of study is that, because they identify the biological pathways, they may include multiple genes, not only one gene. So having identified these pathways we can help the clinician to better decide the recommendation or tailor the recommendation for individual patients.
Another future plan we can do is that, as I mentioned earlier, probably we can now confirm our findings in additional studies. So, in other words, we can conduct another validation study and once we have confirmed our results we can consider to use this finding for clinical care.
Do you have a final take-home message on the use of aspirin?
Aspirin use, many epidemiological studies and randomised clinical trials suggest that aspirin use may prevent colorectal cancer. But, as you know, aspirin has side effects like bleeding so this kind of hazard of aspirin is also very important to consider when you want to use aspirin. So I think in the future we can make a balance and take into account both benefit and hazard of aspirin use and based on that balance we can decide if a patient is better to use aspirin or not. So I think our study is just the beginning for a personalised prevention strategy. So in the future we need to do more studies, as I mentioned earlier, to better make decisions for patient care.
