A new and exhaustive genome-wide association study for colorectal cancer has been published. This work is likely to be the definitive atlas of gene variants contributing to CRC risk: whole genomes were sequenced for 1400 cancer cases and compared to 720 controls. The results were mixed in with previous studies to improve statistical powering – a total of 125,000 genomes were analyzed in total. That’s a number comparable to the number of new cases diagnosed in the US each year, 140,000. I think it’s fair to say that any further variants out there are either exceedingly rare or have little influence on cancer risk, or both.
That phrase “little influence on cancer risk” really sums up the whole project. All of the genetic variants found, which total around a hundred, collectively account for 8-10% of a person’s lifetime colon cancer risk. Lifetime risk for CRC is 4.2% in the US. That makes the genetic contribution to absolute risk about 0.4%. So a genome test for cancer risk – absent any other risk information – would change that lifetime risk to 4.0% if you got all the good variants, or 4.4% if you got all the bad ones. Most of us will fall in between this narrow range. In other words a genome scan for CRC risk would not be actionable. The best case the authors make for utility is that it might justify starting regular screening by endoscopy a few years sooner (or later) than is now recommended. OK, sure.
From Discovery of common and rare genetic risk variants for colorectal cancer
Other than that, this study adds a few new plausible drug targets to the list. Like most genomics, it should provide a rich vein of information for studies on the various pathways and mechanisms that lead to cancer. With so many possible permutations–we have to add in the mutations that arise in cancer cells–this will no doubt be a task best suited for AI.
Since we already knew from familial studies that genetic factors account for 13% or less of colorectal cancer risk, this study doesn’t add anything to our appreciation of genetic vs environmental causes of cancer.
Cancer genomics is quickly becoming a dry hole, and an expensive one at that. When I ran R&D groups, I usually budgeted $250K per FTE per year for total costs. This paper has about 200 authors on it. They did a very thorough job and found 40 new risk markers, bringing the total to 95. But even if the average author only contributed 0.1 FTE, that’s well over $5M of research funding. That funding essentially confirmed the results of familial studies, identified a few potential drug targets, and might lead to a refinement of screening guidelines. Meh.
Genomics was never going to yield the return on investment promised by its enthusiasts. It’s clear now that we are in the last phase of mining the genome for cancer data – there are no remaining mother lodes of insight, just a few flakes and specks to be picked up at great cost and effort. It’s time to cut bait on genomics and focus on environmental causes of cancer.
1 thought on “Genomics keeps being not important for understanding cancer risk”