Table 6.

Studies of colorectal screening in hereditary colorectal cancer (CRC) syndromes

Study (year)	Reference	Subjects	Design	Findings
Lynch syndrome
Järvinen et al. (1995)	(42)	252 At-risk individuals from 20 of 22 families with MMR mutations.	Observational: all invited for colonoscopy screening; 133 had q 3-year colonoscopy, 118 declined.	62% Less CRC in screened (P=0.03). Tumor stage more favorable in screened. No deaths in screened vs. 5 deaths in nonscreened.
Järvinen et al. (2000)	(41)	252 At-risk individuals from 20 of 22 families with MMR mutations.	Observational: follow-up of Järvinen et al. (1995) study	62% reduction in CRC in screened (P=0.02). No deaths from CRC in screened vs. 9 deaths in nonscreened.
De Vos tot Nederveen Cappel et al. (2002)	(48)	857 Members of 114 HNPCC- or MMR-positive families.	Observational: tumor stage with more frequent (≤2 years) vs. less frequent colonoscopy; 10-year risk of CRC with partial vs. subtotal colectomy.	Earlier stage CRC with more frequent colonoscopy. 15.7% risk of CRC with partial vs. 3.4% with subtotal colectomy at 10 years.
Dove-Edwin et al. (2005)	(44)	554 At-risk members of 290 families with HNPCC or MMR mutations.	Prospective observational: evaluation of efficacy of colonoscopy.	Estimated 72% decrease in CRC death in screened individuals.
Jarvinen et al. (2009)	(43)	242 MMR mutation-positive and 367 mutation-negative subjects.	Observational: cancer incidence/survival of 11.5-year follow-up of colonoscopy surveillance	No increase in cancer mortality in mutation-positive vs. -negative individuals.
Familial adenomatous polyposis (FAP)
Vasen et al. (1990)	(325)	230 Confirmed FAP cases	Observational: compared colorectal cancer rates in symptomatic cases vs. family members identified via screening	47% of the symptomatic cases had CRC at a mean age of 35 years compared with 4% at 24 years
Bjork et al. (2000)	(128)	195 Subjects with FAP	Observational: evaluation of rectal cancer morbidity and mortality after colectomy with ileorectal anastomosis (IRA)	The cumulative risk of rectal cancer 20 years after an IRA was 12.1%. There was a 7% cumulative risk of mortality.
Jarvinen (1992)	(82)	251 Affected subjects from 81 FAP families	Observational: evaluation of the effects of family screening on the occurrence of colorectal cancer by comparing cases diagnosed during family screening (call-up group) and symptomatic probands	65.5% Of probands had colorectal cancer compared with 6.6% of the call-up cases. The call-up group had a significantly increased lifetime cumulative survival from age 31 years.
MUTYH-associated polyposis (MAP)
Nascimbeni et al. (2010)	(326)	14 MUTYH-positive subjects	Retrospective observational: to evaluate the risk of cancer or severe polyposis of the rectal stump after total colectomy	11 Cases underwent total colectomy with ileorectal anastomosis and yearly proctoscopic surveillance; no patient developed rectal cancer during surveillance (median duration: 5 years).
Nielsen et al. (2010)	(327)	147 Cases and 272 matched controls	Retrospective: compared survival between cases with MAP colorectal cancer and matched controls with colorectal cancer from the general population	Five-year survival was higher for the MAP colorectal subjects (78% vs. 63%). Survival remained better after adjusting for differences between the groups (hazard ration of 0.48).
Peutz–Jeghers syndrome (PJS; see Table 8)
Juvenile polyposis
Oncel et al. (2005)	(223)	13 Juvenile polyposis cases	Retrospective: to evaluate the long-term outcomes of the surgery in JPS cases who present with symptomatic colonic polyps	Eleven presented with rectal bleeding initially. Five of 10 patients who had initial rectum-preserving surgery required subsequent proctectomy; a total of 8 cases had their rectum removed during the study period. Following their ultimate operations, five patients required multiple polypectomies for recurrent pouch/rectal polyps.
Cowden syndrome
Heald et al. (2010)	(224)	127 PTEN mutation carriers	Retrospective: to describe the gastrointestinal phenotype in a prospective series of PTEN mutation carriers.	Sixty-nine cases had 1 or more endoscopies and polyps were present in 64 (93%). Of the 64, half had hyperplastic polyps and 24 had both upper and lower gastrointestinal (GI) polyps; 9 (13%) cases had colorectal cancer at age <50 years.
Sessile serrated polyposis syndrome
Boparai et al. (2010)	(259)	77 Hyperplastic polyposis syndrome cases	Retrospective: to describe the clinical and pathological features of a large hyperplastic polyposis syndrome (HPS) cohort	In a mean follow-up period of 5.6 years, 1,984 polyps were identified. Colorectal cancer was identified in 27 cases; 22 were diagnosed at initial colonoscopy. Four of the 5 interval CRCs were detected in diminutive serrated polyps (4–16 mm).