Jarvinen HJ, Aarnio M, Mustonen H, et al.. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 118: 829-834

Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
Gastroenterology (Impact Factor: 13.93). 06/2000; 118(5):829-34. DOI: 10.1016/S0016-5085(00)70168-5
Source: PubMed

ABSTRACT Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years.
Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known.
CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05).
Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.

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    • "Currently, prospective data support the benefit of colorectal cancer screening and consensus guidelines recommend colonoscopy every 1–2 years beginning at age 20–25 years until age 40 and then annually thereafter, although age initiation can be increased in patients with MSH6 and PMS2 mutations [1] [11] [12]. Data on the efficacy of endometrial cancer screening are limited; however, annual endometrial biopsy beginning between the ages of 30 and 35 years is an option, especially for MLH1 and MSH2 carriers [1] [13]. "
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    ABSTRACT: Objective To determine comfort and knowledge among obstetrician/gynecologists and general surgeons regarding recommendations for cancer screening for women with Lynch syndrome. Methods A questionnaire on Lynch syndrome was administered to all obstetrician/gynecologists and general surgeons at a hospital in New York, USA. Results Fifty obstetrician/gynecologists and 62 general surgeons completed the survey (67% response rate). Physicians were more comfortable counseling on colon cancer than endometrial cancer screening (51% vs 28%; P < 0.001). Obstetrician/gynecologists were more comfortable than general surgeons counseling patients on endometrial cancer screening (36% vs 21%; P = 0.090) but less comfortable counseling patients on colon cancer screening (36% vs 63%; P = 0.008). There was no significant difference between the specialties in the number of knowledge-based questions answered correctly. Furthermore, there was no correlation between a physician’s perceived knowledge and number of correct answers. Conclusion Most physicians did not report being comfortable counseling about recommendations for endometrial cancer screening. While obstetrician/gynecologists reported greater comfort than general surgeons, we found no significant difference in disease knowledge between the groups. Because appropriate cancer screening can improve the outcomes of patients with Lynch syndrome, physicians must be knowledgeable and comfortable with screening recommendations for both endometrial and colon cancer, regardless of clinical specialty.
    International Journal of Gynecology & Obstetrics 08/2014; 126(2). DOI:10.1016/j.ijgo.2014.02.024 · 1.56 Impact Factor
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    • "Once identified, carriers are recommended annual or biennial colonoscopy screening to reduce CRC risk (de Jong et al. 2006; Jarvinen et al. 2000); and prophylactic hysterectomy and bilateral salpingo-oophrectomy to reduce risk of endometrial and ovarian cancers (Schmeler et al. 2006). Colonoscopy screening reduces risk of CRC by 56 % and death by 65 % (Jarvinen et al. 2000). Conversely, once identified, non-carriers from mutation-carrying families are at population risk of CRC (Win et al. 2012) and can be relieved of the burden of this intensive screening program. "
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    ABSTRACT: People carrying germline mutations in mismatch repair genes are at high risk of colorectal cancer (CRC), yet about half of people from mutation-carrying families decline genetic counselling and/or testing to identify mutation status. We studied the association of quantitative measures of risk perception, risk prediction and self-reported screening colonoscopy in this elusive yet high-risk group. The sample of 26 participants (mean age 43.1 years, 14 women) in the Australasian Colorectal Cancer Family Registry were relatives of mutation carriers; had not been diagnosed with any cancer at the time of recruitment and had declined an invitation to attend genetic counselling and/or testing. A structured elicitation protocol captured perceived CRC risk over the next 10 years. Self-reported colonoscopy screening was elicited during a 45-minute semi-structured interview. Predicted 10-year CRC risk based on age, gender, known mutation status and family history was calculated using "MMRpro." Mean perceived 10-year risk of CRC was 31 % [95 % CI 21, 40], compared with mean predicted risk of 4 % [2, 7] (p < 0.001); this was independent of age and sex (p = 0.9). Among those reporting any medical advice and any screening colonoscopy (n = 18), those with higher risk perception had less frequent colonoscopy (Pearson's r = 0.49 [0.02, 0.79]). People who decline genetic testing for CRC susceptibility mutations perceive themselves to be at substantially higher risk than they really are. Those with high perceived risk do not undertake screening colonoscopy more often than those who perceive themselves to be at average risk.
    Journal of Genetic Counseling 06/2013; DOI:10.1007/s10897-013-9614-2 · 1.75 Impact Factor
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    • "Timely identification of Lynch syndrome is critical as it allows for screening that, according to previously published prospective data, can improve patient outcomes [4] [5] [6]. However, diagnosis is difficult because, with the exception of the cutaneous stigmata in the Muir-Torre syndrome variant (characterized by sebaceous adenomas, sebaceous carcinomas and keratocanthomas), there are no clinical pathognomonic signs. "
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    ABSTRACT: Introduction: Lynch syndrome was first described in the 1950s however until recently it was rarely included in medical school curricula. As a result, many practicing physicians have limited exposure, potentially contributing to significant under diagnosis. As identification of Lynch syndrome prior to malignancy allows for intensified screening, prophylactic surgery and improved patient outcomes, all physicians should be aware of the characteristics of affected families. We aim to determine the overall level of awareness of Lynch syndrome among medical students at an American medical school. Methods: A voluntary and anonymous questionnaire was delivered to students at an American medical school. The survey instrument assessed the respondent's perceived knowledge regarding the genetics and recommended screening for carriers of Lynch syndrome mutations. Results: The questionnaire was distributed to the entire student body (405 students) with a response rate of 50%. Fifty-nine percent of students reported that they had learned about Lynch syndrome; 27% of first year students, 44% of second year students; 90% of third year students and 100% of fourth year students. Of the students familiar with Lynch syndrome, the reported knowledge of the underlying genetics was 46%, available genetic screening, 18%, criteria used to screen for the syndrome, 24%, recommendations for colon screening, 31% and recommendations for endometrial cancer screening, 17%. Conclusion: The majority of medical students surveyed had been exposed to Lynch syndrome and awareness increased over each year of education. Significantly more students were aware of recommendations for colon cancer screening than endometrial cancer screening (32% versus 17%, p = 0.01). Studies of the natural history of Lynch syndrome indicate that affected women are more likely to present with endometrial cancer than colon cancer and while there are no prospective data proving the efficacy of endometrial cancer screening in this high-risk population, the endometrium is easily accessible and can be sampled using simple office techniques. In addition, prophylactic hysterectomy and bilateral salpingo-oophorectomy are reasonable risk reducing interventions for the prevention of both uterine and ovarian cancer. Our findings suggest that increased emphasis must be placed on teaching the gynecologic manifestations of Lynch Syndrome in order to avoid the misconception that it is simply a colon cancer syndrome.
    Current Women s Health Reviews 08/2012; 8(3):242-247. DOI:10.2174/157340412803760667
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