Understanding the Genetics of Cancer

Dr. John J. Lefebre

FRCPC
Medical Consultant
RGA International

Today’s cancer pathology reports commonly refer to “driver mutations” that are either present in or absent from a tumor’s genome. Because of this, it has become vital for insurance company medical directors, underwriters, and claims professionals to acquire at least a basic understanding of genetics and mutations as well as targeted therapies and their mechanisms. With the price of whole genome, whole exome, and other genomic sequencing continuing to drop rapidly, more complicated pathology reports that contain significant amounts of genetic information will need to be correctly interpreted.

With advanced cancers, the use of targeted therapies is not likely to impact how life or critical illness insurance policies are underwritten in the short term, but they could significantly impact the approach to claims adjudication and cost of healthcare-related products.

This article looks at how genetics is contributing to cancer development, treatment, and prognosis. It provides a brief overview of genetics, including commonly used terms, discusses some of the more common genetic mutations, and gives examples of the mutations that occur in cancer.

The following is a terminal illness (TI) claim which will pay if death is expected within the next 12 months:

A 51-year-old male nonsmoker started afatinib (a tyrosine kinase inhibitor) four months ago for an adenocarcinoma subtype of non-small-cell lung cancer (NSCLC).

His pathology reports documented:

• Stage 4B, T3 N3 M1b disease based on PET-positive right hilum, mediastinal, and neck nodes and distant metastases in liver and bones.
• The tumor is ALK-IHC negative, ROS1-IHC negative, PD-L1 10%positive, EGFR ctDNA exon 19 deletion positive.
• First-line immunotherapy is not indicated as the level of PD-L1 is 10%. (Levels 50% or greater would support use.)
• The tumor is positive for EGFR mutation with an exon 19 deletion – hence prescribed afatinib.

This report utilizes molecular profiling of the cancer to a substantial degree. The several genetic mutations identified in the tumor may be therapeutically and prognostically relevant, and may potentially impact the assessment of the Insured’s life expectancy and eligibility for benefits. 

Genetics review

To grasp the impact of genetics on cancer development, treatment, and prognosis, it is important for medical directors, underwriters, and claims managers to review the essentials of genetics and the cancer genome. 

• The basic unit of genetic information is the double-stranded molecule deoxyribonucleic acid (DNA). DNA’s building blocks are called nucleotides. Each nucleotide consists of a phosphate, a sugar, and one of four base molecules: adenine (A), cytosine (C), guanine (G), and thymine (T).
• DNA’s characteristic double helix is formed by pairs of these bases. Cytosine always pairs with guanine (C:G) and adenine with thymine (A:T). Human DNA contains about three billion base pairs, which represent the entire genome and codes for 20,000 to 25,000 genes.
• The nucleotides are grouped together in three-letter code words called codons. Each codon encodes for one amino acid. Amino acids are the building blocks of proteins. This encoding occurs via messenger ribonucleic acid (mRNA) which is “transcribed” from the DNA template and the mRNA is then “translated” into an amino acid.
• Only a small portion, approximately 3% of the human genome, is translated into proteins. This means the majority of the genome is selectively repressed. The portion of the genome that codes information for protein synthesis is called the exome, meaning all the protein coding genes are found in the exome. The actual portion of exome that contains the information used for protein synthesis is call the exon.
• Introns make up the rest of the exome and are found between the exons, but the introns do not contain any protein coding information.

Alterations and mutations in DNA, mRNA and/or the end product protein can make each cancer slightly different.

This article will focus only on cancers caused by DNA-based alterations and mutations.