Screening for people with a family history of colorectal cancerBMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7097.1779 (Published 21 June 1997) Cite this as: BMJ 1997;314:1779
Target invasive screening to younger people with truly high risk
- a Department of Surgery, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
- b University of Edinburgh, Department of Public Health Sciences, Edinburgh EH8 9AG
People with one or more first degree relatives affected by colorectal cancer have an increased risk of developing the disease themselves,1 2 3 especially if a relative was affected at an early age (before age 45).2 3 The excess risk is even more marked if the unaffected person reports a family history when aged less than 45.1. Hence, many centres offer colonoscopy every three years or even more frequently to people fulfilling the following criteria: one first degree relative affected by colorectal cancer before the age of 45; two affected first degree relatives; evidence of dominant familial cancer trait including colorectal, uterine, and other cancers. However, in practice even less restrictive criteria are employed. We wish to highlight some concerns about targeting invasive screening using criteria based on family history and to encourage further debate on this issue.
About 10% of patients with colorectal cancer have one or more first degree relatives who are affected.2 3 People with a family history are twice as likely as the general population to develop colorectal cancer themselves,1 2 3 but there is considerable variation in the risk to each person.1 2 People from families with hereditary non-polyposis colorectal cancer (HNPCC) represent the high end of the risk spectrum. The lifetime risk of colorectal cancer for carriers of the gene is 80%.4 Therefore, anyone belonging to such a family has, without genetic testing, an average risk of cancer of 40%. Colonoscopy provides survival benefit in these families,5 but a screening interval of 12-18 months is essential.6 7 However, recognition of affected families is confounded by lack of pathognomonic features, deficiencies in family information, adoption, early death of relatives due to unrelated causes, and incomplete gene penetrance. The result is that an appreciable proportion of gene carriers do not have sufficient affected relatives to meet faily history criteria for colonoscopy.8 Hence, people with a very high risk of colorectal cancer are not well served by the use of criteria based on family history as a systematic approach to screening.
About 0.4% of the population have two first degree relatives affected by colorectal cancer,1 2 3 representing 105 900 people aged 30-70 in the United Kingdom. Assuming a conservative estimate of four first degree relatives for each patient aged under 45 who presents with colorectal cancer annually in the United Kingdom, we estimate that a further 128 800 relatives fulfill the criteria. With a three yearly screening interval, an extra 78 233 colonoscopies would potentially be required annually at a cost of £11.7m. The resources required are of similar size to those for population screening by faecal occult blood test. We estimate the positive predictive value for identifying cancer at each colonoscopy based on family history criteria to be about 0.32%. This compares poorly with that for faecal occult blood test at 9.9%.9 The United Kingdom National Screening Committee recently convened a series of workshops to determine whether mass population screening by faecal occult blood test merits implementation in the NHS. This structured approach to considering the case for population screening contrasts with the ad hoc implementation of screening for people whose only risk factor relates to their family history.
Focus on cumulative absolute risks
When offering advice to an individual patient regarding the balance of risk and benefit of screening, it is essential to focus on the cumulative absolute risk of cancer in the coming years compared to the cumulative risk of complications from colonoscopy. We have calculated the cumulative risk for the next 10 years of developing and dying from colorectal cancer compared to the risk of complications related to colonoscopy10 for people aged 30, 40, 50, and 60 with two affected first degree relatives or one first degree relative affected under the age of 45 (1). Even though the relative risk of colorectal cancer is high (increased six fold), colonoscopy for people aged 30-49 with a family history is only six times more likely to save them from cancer than it is to kill them from colonoscopy. In addition, screening is considerably more likely to cause a serious complication in all age groups except the group aged 60-69 years. These risk comparisons are in stark contrast to those for a 30 year old male carrier of the gene for hereditary non-polyposis colorectal cancer, for whom we previously reported about a 1 in 1.7 chance of developing cancer by age 49.4 This underscores the variation in absolute risk among people with a family history and the real need to systematically identify people from affected by hereditary non-polyposis colorectal cancer.
It is clear that invasive screening should be reserved for people with a substantial absolute risk of colorectal cancer.7 Systematic case finding of gene carriers by mutation analysis is feasible4 and could now be considered as an efficient approach to screening for people with greatly elevated risk of cancer. This would allow targeting of colonoscopy to people who would gain most from it. When information about gene mutation is not available, enrolment into colonoscopic screening programmes on the basis of family history should be through properly resourced clinical genetics departments to ensure accurate risk assessment and attention to counselling. The balance of risk to benefit means that colonoscopy on the basis of family history should be reserved for people from families with many affected relatives (three or more) showing a dominant mode of inheritance and early onset. People with a family history but who are not from families with hereditary non-polyposis colorectal cancer should be offered non-invasive screening such as faecal occult blood tests at about age 40.10 Programmes raising pubic awareness of family history or encouraging general practitioners and hospital physicians to be proactive in identifying familial cases should be carefully evaluated since there is potential for raising anxiety among a large group who have only marginally increased risk.