Colorectal cancer is a common malignancy of the digestive system with a poor prognosis and a high morbidity and mortality rate. AnteCRC is a personalised test for the risk of colorectal cancer. It predicts individual colorectal cancer risk based on a combination of individual polygenic risks, monogenic variations and lifestyle factors.
Who can benefit from AnteCRC?
The test is suitable for men and women aged 25–80 who have European ancestry.
How frequent is colorectal cancer?
Colorectal cancer is the third most common cancer in Europe with an estimated 368,000 new cases in EU28 in 2018. In 2015, it was the second most common cause of cancer death, killing some 154,200 men and women in the EU. Incidence of colorectal cancer is higher in men than in women and markedly increases with age. More than 2.2 million cases of colorectal cancer and a resulting 1.1 million deaths are projected to occur worldwide by 2030.
The genetics behind colorectal cancer
The heritability of colorectal cancer has been estimated to be around 30%. Family-based studies have identified rare high-penetrance mutations in at least a dozen genes, but collectively, these account for only a small fraction of familial risk. It has long been recognised that people with a family history of colorectal cancer are, on average, twice as likely to develop colorectal cancer as those without a family history of the disease are. Some colorectal cancers are caused by inherited mutations in specific, single high-impact genes such as APC, MLH1, MSH2, MSH6, PMS2, STK11, MUTYH, SMAD4, BMPR1A, PTEN, TP53, CHEK2, POLD1 and POLE. Collectively, mutations in these genes explain around 5–10% of the increased risk.
In recent years, genome-wide association studies (GWAS) have continued to identify single nucleotide polymorphisms (SNPs) that are associated with the increased incidence of colorectal cancer. A recent GWAS published in 2019 raised the number of known independent signals to around 100. Specific SNPs can be combined into a polygenic risk score (PRS) for individual risk estimation. Multiple studies have confirmed the usefulness of PRS in creating predictions of colorectal cancer risk that allow for individual risk stratification.
What are the other risk factors for colorectal cancer?
Besides genetic factors and age, several other factors affect colorectal cancer risk: they include a high-fat, low-fibre diet, alcohol consumption, smoking, obesity and physical activity. High body mass index, body or abdominal fatness and type II diabetes are also seen to potentially affect risk. Other factors that increase risk are longstanding ulcerative colitis and Crohn’s disease, increased alcohol use and excessive consumption of tobacco and processed or red meat.
Colorectal cancer prevention and early detection
A growing number of countries have introduced free population-based colorectal cancer screening programmes over the past several years to target people in their 50s and 60s.
In most countries that use the faecal occult blood test, screening is available every two years. With colonoscopy and flexible sigmoidoscopy, the screening schedule is less frequent, typically every 10 years. Invasive methods, such as colonoscopy, remain the main tools due to their very good diagnostic performance, which enables the detection and removal of precancerous lesions. However, it requires lengthy preparation and is uncomfortable for patients, which causes poorer compliance.
AntePC will be available in the second half of 2019.