Diagnostics & Imaging Week Correspondent

LONDON – Genetic variations that predispose people to five common types of cancer could explain the observation that cancer – not just one sort, but several different kinds – runs in some families.

DeCODE Genetics (Reykjavik, Iceland), which reported finding the cancer variants in Nature Genetics this week, also launched two new tests as part of its "retail" genome-testing service. In addition to a full genome scan, consumers will now also be able to buy two focused tests that can detect genomic variations that affect someone's lifetime risk of developing several major cardiovascular diseases or several common cancers.

Importantly, the variants described in Nature Genetics all affect a gene that is already known to play a role in dictating someone's risk of cancer: that encoding the enzyme telomerase, which is involved in maintaining the lengths of the telomeres.

Telomeres are long, repeated sequences at the ends of linear chromosomes. They protect the chromosome ends from fusing together and from degradation by cellular enzymes, rather like the caps on the ends of shoelaces prevent the laces from becoming frayed and tangled.

In normal human cells, telomeres are several thousand bases long. With each round of cell replication, they become progressively shorter until, eventually, they are too short to allow the cell to divide, and the cell either becomes senescent or undergoes apoptosis.

Telomerase helps the cell to maintain its telomeres. It is not expressed in most adult human cells, but it is active in 90 percent of human cancer cells. Many studies have focused on ways of inhibiting the enzyme in cancer cells, to force them to undergo apoptosis.

Kari Stefansson, CEO DeCODE, told Diagnostics & Imaging Week's sister publication BioWorld International: "Our study shows that certain common single nucleotide polymorphisms (SNPs) are linked to susceptibility to several different types of cancer, including lung, bladder, prostate, skin and cervix. This was an important discovery to make because it sheds light on the observation that there are some families where cancer in general is more common than in the general population, not just cancer affecting one organ."

The SNPs concerned fall close together on chromosome 5p15, in the gene encoding the human telomerase reverse transcriptase (TERT).

Stefansson said: "In our study, we also showed that the sequence variants associated with the various types of cancer are also associated with shorter forms of telomeres than you see in control samples. What also makes the story more robust is that it is well known that those who have short telomeres are less likely to develop malignant melanoma than those who have long telomeres. This is the opposite to what you see with the other cancers linked to these variants, and we did indeed find that the variants are associated with protection from malignant melanoma. So the whole story fits together."

The work is reported in the Jan. 18 issue of Nature Genetics in a paper titled: "Sequence variants at the TERT-CLPTM1L locus associate with many cancer types."

DeCODE began the work for this study with a genome-wide association study to look for variants that were associated with basal cell carcinoma of the skin. This led them to a SNP in the gene encoding cisplatin resistance related protein 9 (CLPTM1L), which lies close to the TERT gene. Because the researchers knew that this region of the genome contains many genes with important roles in cancer biology, the team then decided to carry out a "phenome scan."

Instead of a genome scan, in which researchers look for sequence variants that associate with a particular disease, a phenome scan involves taking a variant in the genome and looking at people with many different diseases to see which phenotype associates with it. This approach allowed them to show that one of the variants associated with a higher risk of basal cell carcinoma also increased the risk of cancer of the lung, bladder, prostate and cervix, while protecting against malignant melanoma.

Stefansson predicted that researchers will be able to use the findings to design better clinical trials to test candidate drugs that aim to inhibit telomerase.

The company is charging $195 for its deCODEme Cardio test and $225 for its deCODEme Cancer test. Stefansson added: "In spite of all our advances in treatment of cancer, the one factor that decides more than anything else what prognosis someone has, who develops cancer, is how early it is diagnosed. Our tests make it possible to identify those who are at highest risk."