We had a very informative but highly technical presentation as below:
Notes of a presentation by Prof. Paul Pharoah
from the SEARCH project based at Strangeways Research Laboratory, Cambridge
There has been a continuous development of the understanding of genetics – from Darwin (natural selection), through Mendel (inheritance in peas) via Miescher (isolation of nucleic acid) to Watson & Crick (DNA).
This has led to the Genome Project, unravelling the mystery of the DNA, the immensely long strings all built on 4 bases or nucleotides, labelled A, T, C and G. DNA is formed of the double helix with matched pairs of bases A-T and C-G. There are some 3 x 109 base pairs in a human genome. As there are two copies in every cell, one from each parent – thus 6x109 base pairs (bp).
They differ, on average, at 1 in 1000 bp – therefore 3,000,000 between any pair of genomes. A variant is called common if it occurs in >5% of genomes.
However, small differences can have large effects – a single change in one bp can lead, for example, to achondroplasia (dwarfism). Sickle cell anaemia is also the result of a mutation in a single nucleotide.
Cancer can run in families with the children at increased risk of the same cancer; the size of the increase in risk varies with the cancer – e.g. testicular cancer 8 times the risk, thyroid 4 times, while breast and prostate at 2 times the risk. There’s a small link between breast and prostate cancer – approx 1.1. But the risks tend to be a combination of genes and the environment together.
The terminology can be confusing:
Germline genetics relates to the genomes passed to offspring.
Somatic genetics relates to tissues other than reproductive cells, so called because the DNA has mutated in some cell(s) and is therefore not the same as in all the other cells and is not passed on to offspring. Angelina Jolie has a fault in the BRCA1 gene which predisposes to breast cancer.
Finding cancer susceptibility variants involves obtaining cases – particularly cancer, in persons of similar age to compare against controls. Some 80 variants have been found with a small risk of prostate cancer. Does this have clinical relevance? There are some common variants and some men carry more than one: there are a few at low risk, a few at high risk but most are in the middle. However, identifying a risk is only useful if we can do something about it!
Drugs? – most wouldn’t want to take these.
What use would universal screening be? – PSA tests are useful for men at high risk or who show symptoms. But simpler and better tests are required – so more research is needed to develop these.