Current Investigations In Cancer Cell Biology Part I: Understanding Relative vs. Absolute Risk

“Science literacy empowers you to know when someone else is full of shit.” - Dr. Neil deGrasse Tyson

As I begin my senior year at UConn, most of my course load consists of graduation requirements, one of which is a writing course on a topic that is outside of my major (Allied Health Sciences). In order to fulfill this requirement, I am taking MCB3842W: Current Investigations In Cancer Cell Biology, in which I will write about cancer biology breakthroughs to meet the 15-page graduation obligation. To my knowledge and delight, my professor is taking an unorthodox approach by breaking these 15 pages into multiple 3-5 page essays, in which myself and my classmates will translate cancer research to the public through lay-style articles. After getting the green light from my professor, I decided that I would share these articles here because they fill a similar role to my other deep dives (check out this one for Immunology 101), in that they will break down complex biology into understandable terms. I plan to use these essays, as well as more deep dives, to explain pivotal and interesting scientific concepts, such as the importance of relative risk vs. absolute risk that I discuss in this first essay. Both my understanding of this topic and my inspiration for this first essay come from Dr. Peter Attia’s emphasis on how comprehending relative risk vs. absolute risk is vital to analyzing and assessing scientific studies. For more on this topic, as well as additional insights into scrutinizing scientific research, check out Attia’s Studying Studies series here.

Misinterpreting Science: Relatively Ground-Breaking Results That Are Absolutely Trivial 

In today’s polarized and decisive world, science often acts like a parent dealing with their disagreeable children, in that it provides the final say in who is “right” and who is “wrong”. Although I believe as much in the power of science as the next person in line, I recognize that this power can cause more harm than good when taken out of context or irresponsibly overexaggerated. 

For example, we have all heard or said something along the lines of, “the research says” or, “according to the science,” with the intention of definitively supporting a claim; however, how often do we use these phrases with appropriate confidence? How often do we actually analyze and dissect research papers, rather than simply taking their headlines or abstracts as concrete facts? 

You may be thinking that you don’t need to scrutinize the articles published in big-name journals, like The New England Journal of Medicine, or by prestigious PhD’s and MD’s because there is no way that such esteemed entities and people could intentionally or accidentally misconstrue data; nonetheless, amidst our modern and media-driven world, I find that scientific data is often misinterpreted.

For example, the authors of this study, published in Gastroenterology this July, claim that their results demonstrate a significant decrease of early-onset colorectal cancer (CRC) associated with higher vitamin D consumption. On the surface, these seem like great results that we can easily implement to reduce our risk of early-onset CRC; however, after digging deeper into the study, you will find that its impact is not so significant.

The researchers conducted a prospective cohort study — meaning that they took a group of similar individuals, divided them into subgroups based on one trait, and followed those subgroups over a period of time — involving 116,429 female nurses between the ages of 25 and 42, all of whom did not have inflammatory bowel syndrome, previous diagnosis of CRC, baseline energy intake below 600 or above 3500 calories per day, or missing baseline data for vitamin D intake. Every 2 years, these individuals completed a questionnaire regarding their demographics, lifestyle, medical information, and other health information; additionally, every 4 years they completed a frequent food questionnaire (FFQ) that covered a week of their dietary intake. Using the results from these questionnaires, the researchers divided their subjects into the following cohorts based on their daily vitamin D consumption: less than 300 IU per day, 300 to 450 IU per day, and greater than 450 IU per day. 

After analyzing their results, the researchers touted a roughly 50% decrease in risk of early-onset CRC for those in the two groups consuming more than 300 IU per day; however, they failed to recognize that this was a change in relative risk, not in absolute risk. 

Relative risk describes the difference in outcomes between groups in a study — in this case, it was the difference in outcomes between groups consuming different amounts of vitamin D. For example, if Group 1 has a 5% risk of developing early-onset CRC and Group 2 has a 10% risk of developing early-onset CRC, then Group 1 has a 50% decrease in relative risk in comparison to Group 2. 

Absolute risk, on the other hand, depicts the net change in total risk between groups. Continuing with the example above, if Group 1 has a 5% risk of developing early-onset CRC and Group 2 has a 10% risk of developing early-onset CRC, then Group 1 has a 5% decrease in absolute risk in comparison to Group 2. As you can see, there can be a large discrepancy in quantity and impact depending upon which of these measurements you are looking at. 

In terms of the study mentioned earlier, this discrepancy is important, as the results demonstrate a roughly 50% change in relative risk but only a measly 0.005% change in absolute risk. Specifically, after crunching the numbers, the study reveals that the risk of developing early-onset CRC decreased from roughly 0.01211% when consuming less than 300 IU of vitamin D per day to roughly 0.00632% when consuming between 300 and 450 IU of vitamin D per day and to roughly 0.00665% when consuming greater than 450 IU of vitamin D per day. 

Despite these trivial results, the authors of the study still expressed that, “Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC”, claiming that their, “results further support that avoiding low vitamin D status is important in younger adults for health and possibly CRC prevention.” (Kim et al., 2021)

In addition, these statements led to the production of overly exuberant review articles, like this one that echoes the same misleading claims. (O'Neill, 2021) If you give the researchers the benefit of the doubt and assume that they genuinely mistook their results as clinically significant, then you are likely not surprised that journalists covering the study also made this error. Yet, it is often through such review articles that research findings and scientific discoveries meet the public eye, so these journalists are equally responsible for assuring that their stories portray both scientifically and statistically accurate information.

This study is one of many examples of how headlines and abstracts can lead us down slippery slopes of inaccurate and irresponsible interpretations of data, or even a lack of interpretation altogether. In this case, the repercussions are less severe, as the study’s claims would only lead to minor dietary changes; however, in other cases, similar misinterpretations of research findings could lead to more harmful interventions or lifestyle changes.   

For this reason, it is important to listen to the famous Neil deGrasse Tyson and improve our scientific literacy, so we can discern truly actionable significance in research findings from trivial outcomes and make better decisions in our lives.