Family History of Colorectal Cancer: It Is Time to Rethink Screening Recommendations

Abstract

See “Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer,” by Schoen RE, Razzak A, Yu KJ, et al, on page 1438. See “Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer,” by Schoen RE, Razzak A, Yu KJ, et al, on page 1438. Clinical practice guidelines recommend initiating routine screening for colorectal cancer (CRC) in people at average disease risk starting at age 50 and repeated at varying intervals depending on the type and results of the test used.1Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med. 2008; 149: 627-637Crossref PubMed Scopus (1229) Google Scholar, 2Levin B. Lieberman D.A. McFarland B. et al.Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.Gastroenterology. 2008; 134: 1570-1595Abstract Full Text Full Text PDF PubMed Scopus (1704) Google Scholar More intensive screening is recommended for those at higher risk because of family history.3Doubeni C.A. Precision screening for colorectal cancer: promise and challenges.Ann Intern Med. 2015; 163: 390-391Crossref PubMed Scopus (7) Google Scholar Specifically, a person with a history of CRC in 1 first-degree relative before age 60, or ≥2 first-degree relatives at any age is recommended to begin screening using colonoscopy every 5 years starting at age 40 or 10 years earlier than the youngest relative's age at diagnosis.4Winawer S. Fletcher R. Rex D. et al.Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence.Gastroenterology. 2003; 124: 544-560Abstract Full Text PDF PubMed Scopus (1985) Google Scholar These recommendations are designed to improve the detection and management of familial cancers in people for whom there is no identifiable inheritable genetic syndrome such as familial adenomatous polyposis or the Lynch syndrome. Family history however becomes less and less important a risk factor for CRC with advancing age.5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar Yet, the guidelines do not specify an age at which such a history no longer justifies more aggressive screening than the average risk population. By implication, therefore, this aggressive approach is used until age 75–85 years, when guidelines recommend screening be stopped. The findings of a new study provide the basis for a more rational approach.7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In this issue of Gastroenterology, Schoen et al7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar report on a study that evaluated whether or not, among older people, having a family history of CRC increased the risk of developing the disease or dying from it. They studied 144,768 men and women aged 55–74 years who participated in the Prostate, Lung, Colorectal and Ovarian (PLCO) trial and were followed for ≤13 years. The study found that people with a family history of CRC had a 1.3-fold higher incidence of CRC than those without such a history. In line with the results of prior studies,5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar the association was weaker with increasing age (relative risk [RR], 1.56 for 55- to 64-year-olds versus 1.25 for 65- to 74-year-olds), although the difference was not statistically significant. The risk was 2-fold higher when ≥2 first-degree relatives were affected, but was only 1.23 with only a single affected first-degree relative. They found similar results in several subgroups including in men and women separately, and according to tumor location or trial arm.7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar This study followed a large number of people over a long period of time and was therefore able to produce reasonably precise estimates of risk according to age of participants and characteristics of affected relatives. It is thus a welcome addition to a growing body of evidence on the risk of CRC associated with having family history of the disease,5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar, 7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 8Butterworth A.S. Higgins J.P. Pharoah P. Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis.Eur J Cancer. 2006; 42: 216-227Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar, 9Johns L.E. Houlston R.S. A systematic review and meta-analysis of familial colorectal cancer risk.Am J Gastroenterol. 2001; 96: 2992-3003Crossref PubMed Google Scholar, 10Samadder N.J. Curtin K. Tuohy T.M. et al.Increased risk of colorectal neoplasia among family members of patients with colorectal cancer: a population-based study in Utah.Gastroenterology. 2014; 147: 814-821 e815Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar with some studies providing evidence on how the risk decreases with increasing age.5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar For example, in a US cohort, the RR associated with having a family history in a first-degree relative was 5.37 at ages 30-44 years and fell essentially to a RR of one in those ≥65 years (Figure 1).5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar Similarly, in a Swedish cohort, among people who were 30-39 years old, those with an affected parent had a 4.79 higher risk of CRC than those without such a history, but the RR was only 1.44 for patients 60-69 years old.6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar Thus, there is a reassuring consistency between Schoen et al’s results and those of previous studies. Although participants in randomized trials are usually not representative of the general population, Schoen et al found a similar prevalence of family history in PLCO participants (10%) as has been reported in other studies.5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar A minor weakness of the study was that information about family history was not updated over the course of the follow-up period, and there was no information on family history for other cancers that are associated with genetic syndromes. Despite the large size, and because CRC incidence and mortality are rare outcomes, the study did not have sufficient power to detect significant differences among subgroups. For instance, the study did not find differences in the association of family history with risk of CRC according to the age at which the relative was diagnosed, but the estimates were imprecise. To put the reported associations of family history in context, the magnitude of excess risk reported by Schoen et al is similar to those reported for some health behaviors. In a large national cohort, the RR of CRC for dietary habits that did not conform to a Mediterranean dietary pattern was 1.91 compared with those who did. Similarly, the RR was 1.44 for physical inactivity, and 1.49 for a body mass index of ≥34 kg/m2 compared with those with a body mass index of <20.11Doubeni C.A. Major J.M. Laiyemo A.O. et al.Contribution of behavioral risk factors and obesity to socioeconomic differences in colorectal cancer incidence.J Natl Cancer Inst. 2012; 104: 1353-1362Crossref PubMed Scopus (141) Google Scholar Yet there are no recommendations for more aggressive screening based on behavioral risk factors or even increasing age beyond 50 years, as there are for family history. The risk of CRC is about 1.8 times higher in people 50-54, compared with 45- to 49-year-olds, but is 5.3, and 7.6 times higher in those 65-69 and 70-74 years old, respectively. To us, the cumulated evidence suggests that patients who are ≥55 years and have only a single first-degree relative with CRC at any age should undergo screening as recommended for average-risk people. This is particularly so for those 65 years and older as evident from Schoen et al, as well as previous studies; in this group, there is no increased risk with only 1 affected family member.5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 6Leu M. Reilly M. Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers.J Natl Cancer Inst. 2008; 100: 1318-1325Crossref PubMed Scopus (25) Google Scholar, 7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar The risk associated with having 2 or more first-degree relatives with CRC is higher (RR, 2.0); fortunately, these patients comprise a relatively small proportion (<1%) of the adult population.5Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (685) Google Scholar, 7Schoen R.E. Razzak A. Yu K.J. et al.Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.Gastroenterology. 2015; 149: 1438-1445Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Our view is that their risk is sufficiently increased to warrant the more aggressive approach with screening colonoscopy, but with caveats. A negative screening test result is a strong negative predictor of future risk,12Brenner H. Chang-Claude J. Seiler C.M. et al.Long-term risk of colorectal cancer after negative colonoscopy.J Clin Oncol. 2011; 29: 3761-3767Crossref PubMed Scopus (107) Google Scholar, 13Singh H. Turner D. Xue L. et al.Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies.JAMA. 2006; 295: 2366-2373Crossref PubMed Scopus (365) Google Scholar including in those with a family history.12Brenner H. Chang-Claude J. Seiler C.M. et al.Long-term risk of colorectal cancer after negative colonoscopy.J Clin Oncol. 2011; 29: 3761-3767Crossref PubMed Scopus (107) Google Scholar Thus, it is reasonable to stop aggressive screening if high-quality screening colonoscopies are repeatedly negative, as is done with surveillance for colorectal adenomas. Patients and clinicians are rightly concerned about missing opportunities to prevent unnecessary death from CRC. Detailed and regularly updated family history information is critical for guiding clinical decisions about appropriate counseling and testing, and the age at initiation and the intensity of screening for patients and family members. A strong family history or evidence for a familial CRC syndrome is a sound basis for aggressive screening starting at a younger age than recommended for average risk individuals, but with increasing age, the relevance of such history wanes. Tailoring screening recommendations in individuals to the best available evidence about their risk as it changes over their life span would be a step forward for precision screening.3Doubeni C.A. Precision screening for colorectal cancer: promise and challenges.Ann Intern Med. 2015; 163: 390-391Crossref PubMed Scopus (7) Google Scholar As clinical practice guidelines are revised, panels should provide more nuanced and evidence-based recommendations for older people with a family history of CRC. Incidence and Mortality of Colorectal Cancer in Individuals With a Family History of Colorectal CancerGastroenterologyVol. 149Issue 6PreviewLittle is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. Full-Text PDF