Early carcinogenic events in HNPCC adenomas: Differences with sporadic adenomas

Rijcken, Fleur Em; Kleibeuker, Jan H.; Hollema, Harry

doi:10.1016/s0016-5085(08)83690-6

Cited by 1 publication

(1 citation statement)

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“…Rijcken et al (118,119) studied 100 HNPCC adenomas (25 from individuals with LS-associated MMR mutations, and 75 from individuals chosen from AC-I families) compared with 152 sporadic adenomas. Fifty percent of colonic adenomas in the HNPCC cases were found in the proximal colon, compared with 26% in sporadic cases.…”

Section: Colon Surveillancementioning

confidence: 99%

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

et al. 2009

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More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (~30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70-80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40-60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/ carcinomas (Muir-Torre variant). LS explains only 10-25% of familial CRC. Keywords colorectal cancer; endometrial cancer; hereditary cancer; hereditary nonpolyposis colorectal cancer; immunohistochemistry; Lynch syndrome; microsatellite instability; mismatch repair; mismatch repair genesThe estimated annual worldwide incidence of colorectal cancer (CRC) is 1,023,152 (1). Lynch syndrome (LS), previously called hereditary non-polyposis colorectal cancer or HNPCC, accounts, conservatively, for approximately 3% (2) of this incidence (~30,700 cases), compared with familial adenomatous polyposis (FAP) syndrome which is about one-tenth as common, occurring in only about 1 in 10,000 of the population (3,4). Hampel et al. studied 500 tumors from unselected CRC affected individuals. Among these 500 CRC patients, 18 (3.6%) had LS. When these results were added to data on 1066 previously studied patients, the entire study cohort (N = 1566) showed 44 patients (2.8; 95% confidence interval (CI), 2.1-3.8) manifesting LS. These authors concluded that approximately 1 in every 35 patients who NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript manifested CRC had LS (2). Given the mentioned worldwide incidence figures of CRC, and extrapolating from the findings of Hampel et al. that 2.8% of the CRC cases they investigated were confirmed to be LS, we arrive at a figure of approximately 28,600 cases of LS to be newly diagnosed this year, worldwide. We have only crude estimates of familial CRC, as defined by the presence of two or more first-degree relatives with CRC, but it is thought by some to involve approximately 20% of all cases of CRC (5,6). These statistics are important given that each hereditary case comes from a family that could benefit from genetic counseling, DNA testing, surveillance, and targeted management (7-9). Yet, when a patient's family risk is overlooked, so too are opportunities fo...

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Section: Colon Surveillancementioning

confidence: 99%