In the United States, colorectal cancer (CRC) is the third most common and second most lethal cancer. More than one-tenth of CRC cases (11% of colon cancers and 18% of rectal cancers) have a young ...onset (ie, occurring in individuals younger than 50 years). The CRC incidence and mortality rates are decreasing among all age groups older than 50 years, yet increasing in younger individuals for whom screening use is limited and key symptoms may go unrecognized. Familial syndromes account for approximately 20% of young-onset CRCs, and the remainder are typically microsatellite stable cancers, which are more commonly diploid than similar tumors in older individuals. Young-onset CRCs are more likely to occur in the distal colon or rectum, be poorly differentiated, have mucinous and signet ring features, and present at advanced stages. Yet, stage-specific survival in patients with young-onset CRC is comparable to that of patients with later-onset cancer. Primary care physicians have an important opportunity to identify high-risk young individuals for screening and to promptly evaluate CRC symptoms. Risk modification, targeted screening, and prophylactic surgery may benefit individuals with a predisposing hereditary syndrome or condition (eg, inflammatory bowel disease) or a family history of CRC or advanced adenomatous polyps. When apparently average-risk young adults present with CRC-like symptoms (eg, unexplained persistent rectal bleeding, anemia, and abdominal pain), endoscopic work-ups can expedite diagnosis. Early screening in high-risk individuals and thorough diagnostic work-ups in symptomatic young adults may improve young-onset CRC trends.
Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for ...diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps.
Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection.
9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection.
Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.
Colorectal Cancer in the Young Patel, Swati G.; Ahnen, Dennis J.
Current gastroenterology reports,
04/2018, Letnik:
20, Številka:
4
Journal Article
Recenzirano
Purpose of Review
Colorectal cancer incidence has been rapidly rising in those under the age of 50 over the last 20 years. This paper will review the epidemiology, clinicopathologic, molecular ...features, proposed risk factors, and prevention/treatment approach for early onset CRC (EOCRC) patients.
Recent Findings
EOCRC appears to have a different spectrum of clinical, pathologic, and molecular presentation compared to CRC diagnosed in older individuals. EOCRCs are disproportionately located in the distal colon; these patients tend to present with symptoms, and there is a longer interval between symptoms and diagnosis. There may be a distinct molecular signature, including progression through the microsatellite and chromosomal stable (MACS) pathway and LINE-1 hypomethylation for a subset of EOCRCs. The majority of EOCRCs are sporadic without clear risk factors that would have made the patient eligible for earlier screening.
Summary
There is an acute need for educational efforts aimed at both providers and patients to raise awareness about CRC in the young. Improving adherence to screening in young patients eligible for screening and emphasizing early evaluation of symptoms are important steps to decreasing the burden of CRC in younger patients. Modeling and empiric data are needed to determine whether our current screening approach should be modified and whether causation and treatment options may be different in a molecular subset EOCRCs.
Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and
) account for some familial aggregation of colorectal cancer, their population prevalence and the ...causes of the remaining familial aggregation are not known.
We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and
We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis. We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic component.
We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (
= 1 in 1,946,
= 1 in 2,841,
= 1 in 758,
= 1 in 714), 1 in 45 carry mutations in
, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes. The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 3.3 for age <40 years to 0.5 for age ≥70 years (equivalent to sibling relative risks of 5.1 to 1.3, respectively).
Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancer.
Our findings could aid gene discovery and development of better colorectal cancer risk prediction models.
.
Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a ...disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.
Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive ...potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas.
We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy.
Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval CI, 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events.
Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).
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