High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer

Abstract

Purpose Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. Patients and Methods We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. Results Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. Conclusion We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.

Colorectal cancer in the young, many questions, few answers

“…In the absence of definitive genetic testing, a detailed family history was essential and formed the core of the Amsterdam and Bethesda criteria to make a diagnosis of HNPCC [28,29] . Currently, we know that young patients with an underlying genetic syndrome are more likely to have a family history of cancer and present earlier compared with those with no known genetic syndrome, who presented with late stage metastatic disease [30] . Thus, family history must continue to remain an essential component of clinical evaluation in patients with CRC, while it is essential to note that up to 20 percent of patients with a germline mutation in the study reported by Mork et al [30] had no family history of CRC.…”

“…In young patients, CRC is likely to be found in those with a heritable syndrome [28][29][30] such as FAP and HNPCC.…”

“…Historically, in the sporadic subtype, the origin of CRC was attributed to various common or rare genetic alterations that displayed variable penetrance, and remained largely unidentified [45] . It is now estimated that up to 30% of CRC may have a hereditary component, with identifiable genetic aberration, especially if cancer occurs in the young [23,24,30,46] . Next generation sequencing (NGS) is likely to further increase our knowledge of hitherto unidentified chromosome aberrations in association with cancer [47] resulting in such diagnoses as the Li-Fraumeni syndrome, Cowden's disease, Juvenile polyposis and Peutz-Jegher syndrome [46] .…”

The impact of young adult colorectal cancer: incidence and trends in Colorado

“…Although the traditional paradigm of CRC tends to center around environmental factors such as increased red meat intake and exposure to carcinogens [14], there is evidence of a higher prevalence of genetic risk factors such as Lynch syndrome and familial adenomatous polyposis in YA CRC cases [5]. Additionally, as overall CRC incidence has declined, disparities between racial and ethnic groups have been revealed, as well as variations in race-specific mortality rates [12].…”

“…There is currently no consensus in the literature regarding the definition of young-onset CRC; however the rising incidence in adolescents and YAs has recently attracted increased attention from physicians, public health officials and investigators [5,12,13]. Although the traditional paradigm of CRC tends to center around environmental factors such as increased red meat intake and exposure to carcinogens [14], there is evidence of a higher prevalence of genetic risk factors such as Lynch syndrome and familial adenomatous polyposis in YA CRC cases [5].…”