Cancer — 8

By the age of 65 years, 10 percent of the participants with pathogenic or likely pathogenic variants in cancer genes had died. In contrast, in the group of participants without such a variant, 10 percent had died by 73 years of age.

Of note, results were analyzed from only seventy-three genes, which are currently considered by the American College of Medical Genetics and Genomics as actionable but represent a tiny (0.3%) proportion of the approximately twenty thousand genes in our genome. The Healthy Oregon project of whole genome population sequencing included some additional cancer genes in its reporting and found 5 percent of its cohort had a pathogenic or likely pathogenic cancer gene mutation. An assessment of population sequencing for three common hereditary conditions—breast cancer and ovarian cancer, Lynch syndrome, and familial hypercholesteremia—was found to be cost-effective for people younger than forty.

Some biomarkers can be used that are associated with a higher risk of specific cancers, such as proteins for risk of pancreatic cancer or a circulating microbiome DNA for lung cancer. Clonal hematopoiesis of indeterminate potential, clones of blood stem cells with driver gene mutation frequency ≥2 percent, is one such example, and it can be derived through genome sequencing. Its presence, which is increasingly common with aging, carries an elevenfold risk for blood cancer and increased risk of lung cancer and nonmelanoma skin cancer. Like so many other potential biomarkers, CHIP is featured in hundreds of research publications in leading biomedical journals but has yet to find its way into the clinic as a marker of increased risk. Similarly, inflammatory markers like high-sensitivity C-reactive protein (hs-CRP) are not used to assess risk of cancer, despite supportive data, and a large trial of a monoclonal antibody directed against a key protein interleukin-1β, to suppress inflammation, significantly reduced fatal cancers and lung cancer, even though it was designed to reduce cardiovascular events. A main criterion for enrollment of the ten thousand participants was an elevated hs-CRP. The results tell us that directly measuring inflammation markers in the blood for directing anti-inflammatory treatment has considerable potential to lessen the toll of cancer. It also represents something else we don’t do today and are not pursuing with better biomarkers and drugs.