What’s the Risk?

Last week, we published a meta-analysis that found that high exposure to glyphosate-based herbicides was associated with an increased risk of non-Hodgkin Lymphoma (NHL). There was a lot of discussion about this paper in the news, on social media, and across internet forums (as expected, given the ongoing controversy and high stakes of this conclusion). Most articles focused on the specific risk estimate that we reported, with headlines such as:

Glyphosate exposure increases cancer risk up to 41%, study finds

Weedkiller raises risk of non-Hodgkin lymphoma by 41%”

Common weed killer increases cancer risk by almost half” 

A common critique of these headlines (and our article) was that they (and we) were being misleading, because we reported the 41% increased relative risk of NHL – which sounds very scary!—rather than a 0.8% increased absolute risk of NHL – which sounds less scary.

At the risk of more undue attention on the 41% number (which as I said in my previous post, is less important than the finding of a significant association itself), let me explain a few things about (1) how we report results in epidemiological research, (2) why small increases in risk matter, and (3) how agencies like the Environmental Protection Agency (EPA) regulate on risk.

Relative risks vs. absolute risks

In epidemiology, we are trying to understand whether an exposure is associated with a disease. To do this, we compare the disease rate in the exposed group with the disease rate in the unexposed group.  This ratio gives us the relative risk of disease between the two groups.

[Side note: this is why it is crucial for researchers to select an appropriate comparison group! The relative risk depends entirely on this decision! If your comparison group has an unusually high rate of cancer, you will get a very skewed (and wrong) answer about the effects of the exposure.]

This relative risk, however, does not give us any information on the absolute risk of the disease at the individual level. It only tells us whether the exposed group has a higher or lower chance of developing the disease than the comparison group. In our paper, we report that individuals with high exposure to glyphosate-based herbicides (for example, people who spray it daily for many years) have a 41% increased risk of developing NHL over their lifetimes, compared to those who were not highly exposed (infrequent or no history of use).

The absolute risk, by contrast, tells us the actual risk of the disease for a given level of exposure. This is much more intuitive. For example, on average in the US, approximately 2 out of every 100 people develop NHL during their lifetime. So, the absolute risk of NHL over a lifetime is 2%. Therefore, when our study reports a 41% increased risk for those who are highly exposed, that is equivalent to saying that these individuals now have an absolute risk of 2.8% risk of NHL.

These statistics are communicating the same basic information, but they sound very different. In our epidemiology courses, we learn that absolute risk is better for communicating to the public because it is easier to understand. But, because of the way that epidemiological studies are designed (comparing disease rates in one group vs. the other), our default is to report relative risks. And because we are used to thinking about these ratios, we don’t always realize that this information can be misinterpreted, misunderstood, and confusing. Maybe we should report both metrics in our abstracts.

Nevertheless, both ways of talking about risk give us the same answer to the central question of carcinogenicity: evidence suggests that glyphosate exposure is associated with an increased risk of cancer.

Why seemingly low risks are still important

Some environmental exposures have very high relative risks. Individuals exposed to high levels of asbestos in their homes, for example, have an 800% increased risk of developing mesothelioma, a very rare type of lung cancer.

Most common environmental exposures, however, are associated with relatively small increased relative risks. Let’s take a look at air pollution, a very common exposure. And more specifically, fine particulate matter (PM2.5), very tiny particles emitted from vehicles, industrial facilities, and fires. While exact estimates vary based on the population studied, an increased concentration (of 10 ug/m3, to be exact) in 24-hour average PM2.5 has been associated with a 0.4%-1.0% increased risk of death (mostly from cardiovascular disease). An increase (again, of 10 ug/m3) in long term average PM2.5 has been associated with an overall 10% increased risk of death.

Those seem like small changes in risk. So, can we stop worrying about air pollution?

No, definitely not.

Low relative risks applied to large populations can be extremely consequential. We are all exposed to air pollution. Everyday. And all of those exposures add up. In fact, PM2.5 was ranked as the 5th most important cause of death around the world in 2015, accounting for approximately 4.2 million deaths.

Glyphosate-based herbicides are the most heavily used herbicides in the world, with an estimated 1.8 billion pounds applied in 2014. Most of this usage is on commercial agricultural farms by workers with potentially high cumulative exposures over their lifetimes. Given the large number of people possibly exposed, any significant increase in risk – especially the 41% estimate that we report – is meaningful to consider at the population level.

Regulating risk

Finally, I want to bring up a point about cancer risk in relation to regulations. The US EPA and Food and Drug Administration (FDA), among other agencies, have to manage and regulate risks for the population. For most scenarios, they have decided that an “acceptable risk” for a carcinogen in the general population is between 1 in a million and 1 in 10,000 (over a lifetime).  In other words, EPA and FDA are supposed to take action to prevent exposure to carcinogens that would result in risks higher than those rates (the specific threshold depends on the scenario and, sometimes, technologic feasibility).

Our findings suggest that the absolute risk of NHL over a lifetime might shift from approximately 2% to 2.8% with high exposure to glyphosate-based herbicides. This difference represents an increase of 8/1000 – certainly above EPA’s threshold of concern for the general population.

Note, however, that some of the studies in our meta-analysis were focused on people using glyphosate in commercial agricultural settings. EPA usually allows a higher risk of cancer in occupational scenarios, approximately 1 in 1000. Even with that standard, however, our results would suggest a need for action.

I’m just using these comparisons to put our results in context, because many people seemed to discount this work because of the small absolute risk estimates. Before any actual regulatory action, EPA would need to consider extensive evidence on hazard and exposure in a formal risk assessment.


In closing, I hope that I’ve clarified a few points about risk that were raised in the aftermath of the glyphosate publication. But once again, let me emphasize that you should not focus too much on the specific numerical estimates above but rather use them to better understand that:

  • Relative risks are different than absolute risks. Epidemiologists usually use relative risks, so that is what you will see in published papers (and, likely, the headlines as well).
  • Exposures with low relative risks can still have huge impacts at the population level.
  • Regulatory agencies set certain benchmarks for acceptable lifetime cancer risk in the population. You might not agree with the thresholds, but those are the standards. Keep that in mind when you are reading about risks from environmental exposures.

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