J Hill

Central Manchester University Hospitals NHS Foundation Trust, Manchester, England, United Kingdom

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Publications (28)103.83 Total impact

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    ABSTRACT: Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome with a 60–80% lifetime risk of colorectal cancer. We assessed the uptake of predictive testing and colorectal screening among first-degree relatives (FDRs) in LS families and explored novel methods for informing and engaging at-risk relatives. Uptake of predictive testing was explored using Kaplan–Meier analysis and engagement with colorectal screening was ascertained. A questionnaire was distributed to 216 general practitioners (GPs) of registered LS family members to determine their prior experience and opinion of an enhanced role. Of 591, 329 (55.7%) FDRs had undergone predictive testing. Uptake was significantly lower in males (p = 0.012) and individuals <25 years (p < 0.001). Mutation carriers were more likely to undergo colorectal screening than untested FDRs (97.2% vs 34.9%; P ≤ 0.0001). Of 216, 63 (29.2%) questionnaires were returned. Most GPs (55/63; 87.3%) were not confident to discuss the details of LS with patients and relatives. The main barriers were lack of knowledge and concerns about confidentiality. Compliance with colorectal screening is excellent following a mutation positive predictive test. Uptake of predictive testing could be substantially improved, particularly among males and younger age groups. GPs are unlikely to actively participate in communication with at-risk relatives without considerable support.
    Clinical Genetics 02/2015; DOI:10.1111/cge.12559 · 3.65 Impact Factor
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    ABSTRACT: Background There is a paucity of qualitative literature investigating people's experiences of food and nutrition after treatment for cancer. The present study aimed to explore people's relationships with food and nutrition throughout their colorectal cancer journey.Methods In-depth semi-structured interviews were conducted with 25 participants who had undergone surgery for colorectal cancer. The study design was informed by principles of phenomenology. Data were collected then transcribed and analysed using an inductive coding process and a thematic analysis to allow the themes to highlight people's lived experiences.ResultsData enabled five primary themes to be drawn including: ‘appetite swings’, ‘emotions on a changing physicality’, ‘the medicalisation of food’, ‘taking control of symptom management’ and a cross-cutting theme ‘drivers and vehicles for action’. Feelings and emotions described by participants around their relationship with food and nutritional status often guided decisions on what was eaten more than objective nutritional measure or dietary advice. Participants used weight changes, appetite and food as barometers to measure their overall recovery. Food was an area over which people exhibited control of their lives and they could quantify, in measurable units, their overall well-being and rehabilitation. They did this either by using the currency of body weight in pounds or the size of portions eaten.Conclusions Appetite, weight and symptoms influenced dietary intake substantially and were poignant issues affecting people's lives. The relationship people have with food determines their eating habits and an understanding of the essences and nuances of their experiences is essential to enable the delivery of patient-centred care.
    Journal of Human Nutrition and Dietetics 01/2015; DOI:10.1111/jhn.12291 · 2.07 Impact Factor
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    ABSTRACT: Lynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations.
    Journal of Medical Genetics 10/2014; DOI:10.1136/jmedgenet-2014-102552 · 5.64 Impact Factor
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    ABSTRACT: AimColonic surveillance reduces life time risk of colorectal cancer from 60-80% to 10% and confers a seven-year survival advantage in patients with Lynch syndrome (HNPCC). The British Society of Gastroenterologists recommends colonoscopy at least every two years from age 25. Currently in the UK, genetic diagnosis is made by a regional genetics service and screening recommendations are made to the referring clinician. The aim of this study was to investigate compliance with and the effectiveness of large bowel surveillance in Lynch syndrome.MethodA retrospective longitudinal study of Lynch syndrome mutation carriers on the Regional Familial Colorectal Cancer Registry under and not under screening was conducted. To investigate screening compliance, patients were included if alive at the start of the study. Data were gathered on timeliness, quality and outcome of screening. To examine the effectiveness of screening, the cumulative incidence of colorectal cancer was estimated using Kaplan-Meier and the screened population compared to that in patients not being screened.Results227 Lynch Syndrome mutation carriers were under screening at 26 hospitals. 439 colonoscopies were assessed for timeliness of which 68% were compliant (interval <27 months). Compliance on 01/11/2011 was 87%. Cumulative incidence of colorectal cancer to age 70 was 25% (95% CI 17-32%) in the surveillance population and 81% (95% CI 78-84%) in 689 mutation positive patients not being screened (p<0.0001).Conclusion Overall 68% of colonoscopies were on time. The incidence of colorectal cancer was greatly reduced by screening but remained significant. Lynch syndrome patients need pro-active surveillance management.This article is protected by copyright. All rights reserved.
    Colorectal Disease 09/2014; 17(1). DOI:10.1111/codi.12778 · 2.02 Impact Factor
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    ABSTRACT: The UK National Screening Committee has suggested that screening for anal intraepithelial neoplasia (AIN) in populations at high-risk of anal squamous cell carcinoma may be of benefit, but that further information is needed. In these groups the risk of developing anal cancer is increased up-to 100-fold.
    Gut 06/2014; 63(Suppl 1):A35-A36. DOI:10.1136/gutjnl-2014-307263.71 · 13.32 Impact Factor
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    ABSTRACT: The British Society of Gastroenterology recommends that all familial adenomatous polyposis (FAP) and Lynch syndrome (LS) families are screened in the context of a registry. This systematic review was performed to appraise the published evidence for registration and screening in relation to colorectal cancer (CRC) incidence and mortality. Five electronic databases were searched using a combination of medical subject heading terms and free-text keywords. Titles and abstracts were scrutinized by two independent reviewers. Inclusion criteria were English-language studies describing CRC incidence and/or mortality in patients with FAP or LS, with comparison of either: screened and unscreened patients, or time periods before and after establishment of the registry. Of 4668 abstracts identified, 185 full-text articles were selected; 43 studies fulfilled the inclusion criteria. No randomized clinical trial evidence was identified. For FAP, 33 of 33 studies described a significant reduction of CRC incidence and mortality with registration and screening. For LS, nine of ten studies described a reduction of CRC incidence and mortality with registration and screening. Five studies (FAP, 2; LS, 3) provided evidence for complete prevention of CRC-related deaths during surveillance. Clinical and statistical heterogeneity prevented pooling of data for meta-analysis. Studies consistently report that registration and screening result in a reduction of CRC incidence and mortality in patients with FAP and LS (level 2a evidence, grade B recommendation). Funding and managerial support for hereditary CRC registries should be made available. Presented to the Association of Surgeons of Great Britain and Ireland 2013 Congress, Glasgow, UK, May 2013, and to the Annual Meeting of the Association of Coloproctology of Great Britain and Ireland, Liverpool, UK, July 2013; published in abstract form as Br J Surg 2013; 100(Suppl 7): 123-124 and as Colorectal Dis 2013; 15(Suppl 1): 4.
    British Journal of Surgery 12/2013; 100(13):1719-31. DOI:10.1002/bjs.9316 · 5.21 Impact Factor
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    ABSTRACT: Urological tumours are the third most frequent malignancy in Lynch syndrome after colonic and endometrial cancer. Upper urinary tract tumours are well recognised in Lynch syndrome, but the association with prostate and bladder cancer is controversial. We determined the incidence and cumulative and relative risks of prostate and bladder cancer in a cohort of Lynch syndrome families. Male Lynch syndrome mutation carriers and their genetically untested male first degree relatives (FDR) were identified from the Manchester Regional Lynch syndrome database (n = 821). Time to the development of urological cancer was identified for each urological site (renal pelvis, ureter, bladder and prostate). Cumulative and relative risks were calculated, with results classified by mutation carrier status and specific causative genetic mutations. Eight prostate cancers were identified, only one occurring before the age of 60. Analysis of person-years at risk of prostate cancer by Lynch syndrome mutation carrier status suggests a correlation between MSH2 mutation carriers and a tenfold increased risk of prostate cancer (RR 10.41; 95 % CI 2.80, 26.65). No such association was found with bladder cancer (RR 1.88; 95 % CI 0.21, 6.79). The association of upper urinary tract tumours with MSH2 and MLH1 mutations was confirmed. We have carried out the largest study of male Lynch syndrome mutation carriers to establish the risks of urological malignancy. A tenfold increased risk of prostate cancer is supported in MSH2 with mutation carriers having roughly double the risk of prostate cancer to FDRs. A trial of PSA testing in MSH2 carriers from 40 to 50 years may be justifiable.
    Familial Cancer 10/2012; 12(1). DOI:10.1007/s10689-012-9573-z · 1.62 Impact Factor
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    ABSTRACT: Aim:  Life-time risk of a metachronous colorectal cancer (CRC) is 0.6%-3% following sporadic CRC and 15-26% in Lynch syndrome (LS). The life-time incidence of CRC in individuals with moderate familial risk is 8-17%. Risk of metachronous CRC (mCRC) is unknown. Method:  A retrospective longitudinal study of the Regional Familial CRC Registry was performed. Patients who had at least one CRC were categorised as follows: moderate risk (n=383), LS (n=528) and population risk (n=409). Kaplan-Meier estimate (1-KM) and cumulative incidence function (CI) were used to calculate the risk of mCRC. 1-KM gives the risk for individuals remaining at risk (alive) at a given time point thus is useful for counselling. CI gives the risk for the whole population. Results:  1-KM and CI demonstrated that the risk of mCRC was significantly higher in moderate risk patients compared with population risk (1-KM p= 0.008, CI p= 0.00097). Both were lower than LS. Moderate risk 1-KM was 2.7%, 6.3% and 23.5% at 5,10 and 20 years. Population risk 1-KM was 1.3%, 3.1% and 7.0% at 5, 10 and 20 years and CI was 0.3%, 0.6% and 2.4%. Conclusion:  These data indicate that the risk of mCRC is significantly higher in patients with a moderate family history than in those at population risk. This justifies pro-active life-long surveillance. © 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.
    Colorectal Disease 09/2012; 15(3). DOI:10.1111/codi.12005 · 2.02 Impact Factor
  • J A Barker, J Hill
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    ABSTRACT: As an alternative to more radical abdominal surgery, transanal endoscopic microsurgery (TEM) offers a minimally invasive solution for the excision of certain rectal polyps and early-stage rectal tumours. The patient benefits of TEM as compared to radical abdominal surgery are clear; nevertheless, some drawback is possible. The aim of our study was to determine the risk factors, treatment and outcomes of rectal stenosis following TEM. We analysed a series of 354 consecutive patients who underwent TEM for benign or malignant rectal tumours between 1997 and 2009. We recorded the maximum histological diameter of the lesion, and whether the lesion was circumferential. Rectal stenosis was defined as a rectal narrowing not allowing passage of a 12 mm sigmoidoscope. Histological results with a measured specimen diameter were available in 304 of the 354 cases. There were 11 stenoses in total (3.6%), 7 stenoses due to 9 circumferential lesions (78%) and 4 due to lesions with a maximum diameter ≥ 5 cm (3.2%). Two patients presented as emergencies, and the other 9 patients reported symptoms of increased stool frequency at follow-up. Three of the stenoses were associated with recurrent disease. All stenoses were treated by a combination of endoscopic/radiological balloon dilatation or surgically with Hegar's dilators. A median of two procedures were required to treat stenoses until resolution of symptoms. Rectal stenosis following TEM excision is rare. It is predictable in patients with circumferential lesions but is rare in patients with non-circumferential lesions with a maximum diameter ≥ 5 cm. It is effectively treated with surgical or balloon dilatation. Most patients require repeated treatments.
    Techniques in Coloproctology 06/2011; 15(3):281-4. DOI:10.1007/s10151-011-0703-7 · 1.34 Impact Factor
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    ABSTRACT: Familial adenomatous polyposis (FAP) has been divided into three clinical subtypes: mild, classical and severe. This study aimed to investigate for a correlation between genotype and phenotype. A codon-specific survival difference is unknown. A retrospective longitudinal study of 492 patients on the Manchester Polyposis Registry was conducted. Patients were grouped according to genotypes: 0, unknown mutation; 1, adenomatous polyposis coli (APC) 0-178 (and 312-412 of exon 9); 2, APC >1550; 3, APC 179-1249; 4, APC 1250-1549; and 5, MutYH. Date of onset of polyposis, incidence of colorectal cancer (CRC), survival and actuarial time to surgery were calculated. Median age of onset of polyposis for genotype 0 was 20.3 years, genotype 1 35.6 years, genotype 2 32.2, genotype 3 15.9 years, and genotype 4 14.8 years (p < 0.0001). Age of onset of CRC was similar between genotypes. Median survival for genotype 0 was 56.6 years, genotype 1 74.9 years, genotype 2 61.0 years, genotype 3 63.0 years, genotype 4 48.1 years, and genotype 5 69.7 years (p = 0.003). This survival difference was also seen when patients who underwent screening and those who did not were analysed separately. Survival in the screened population was 53.9 years in genotype 4 and 72.9 years in genotype 3. Patients with genotype 4 (APC 1249-1549) have a significantly worse survival despite screening and early prophylactic surgery. This analysis supports a genotype-phenotype correlation. Patients with a mutation APC 1249-1549 develop polyposis at an early age and have a worse survival. Patients with a mutation APC 0-178 or 312-412 develop polyposis later and have an improved survival. This survival difference has not previously been documented.
    Clinical Genetics 06/2011; 81(6):521-31. DOI:10.1111/j.1399-0004.2011.01740.x · 3.65 Impact Factor
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    ABSTRACT: Perioperative oral supplementation has been shown to reduce post-operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group. In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post-operative complications. One hundred and twenty-five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded. In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group (P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively (P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively (P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight-losing patients, where there was a significant reduction in surgical site infections using the Buzby definition (P = 0.034), although this was not the case for the Centre for Disease Control definition (P = 0.052). There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight-losing preoperative patients.
    Journal of Human Nutrition and Dietetics 06/2011; 24(5):441-8. DOI:10.1111/j.1365-277X.2011.01188.x · 2.07 Impact Factor
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    ABSTRACT: Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs). Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining. Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P = .186 Chi2). The familial group demonstrated significantly less over all methylation levels (P = .004 Chi2). Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.
    06/2011; 2011:653163. DOI:10.1155/2011/653163
  • Clinical Nutrition Supplements 01/2011; 6(1):114-114. DOI:10.1016/S1744-1161(11)70291-5
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    ABSTRACT: Regular colonic surveillance of familial adenomatous polyposis (FAP) patients is necessary to ensure appropriate prophylactic surgery is performed before colorectal cancer (CRC) develops. Polyposis Registries have been established to coordinate screening programmes. The aim of this study was to assess the effect of screening and of the formation of the Registry on survival, incidence of CRC and age at onset of CRC, in FAP patients. Patients on the Manchester Polyposis Registry were categorised according to their mode of presentation; screening or symptomatic, and survival time from birth was calculated for each patient (n=353). The effect of the formation of the Registry was assessed by comparing survival times from birth for patients diagnosed in the 20 years before the establishment of the Registry, to patients diagnosed in the 20 years since the formation of the Registry (n=273). This study demonstrated that survival was increased from 57.8 years to 70.4 years (p<0.001) by screening, and from 58.1 years to 69.6 years (p=0.007) following establishment of the Polyposis Registry. The incidence of CRC was reduced from 43.5% to 3.8% by screening, and from 28.7% to 14.0% following establishment of the Polyposis Registry. Although direct causation between improved survival and reduced CRC incidence, and establishment of the Registry cannot be proven, an association has been demonstrated. Colorectal cancer was found to develop, on average, 16 years later in the screening population. A regular systematic large bowel screening programme, managed by a Polyposis Registry, significantly improves the prognosis of FAP.
    Gut 10/2010; 59(10):1378-82. DOI:10.1136/gut.2010.212449 · 13.32 Impact Factor
  • K F Newton, W Newman, J Hill
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    ABSTRACT: Advances in molecular technology have resulted in the discovery of many putative biomarkers relevant to colorectal cancer (CRC). Literature searches were performed on PubMed and EMBASE using the words 'colorectal cancer', AND 'biomarkers OR markers'. Biomarkers that are either currently in clinical use or have potential clinical use were identified. Most potential markers are in the discovery phase waiting to undergo clinical validation. Hypermethylation of the plasma septin-9 gene shows promise as a nonstool-based screening tool. Hypermethylation of the DYPD gene (encodes the enzyme dihydropyrimidine dehydrogenase) and variation of the uridine diphosphate-glucuronosyltransferase 1A (UGT1A1) gene have predictive value for side effects and the efficacy of 5-fluoruracil and irinotecan, respectively. Mismatch repair protein immunohistochemistry is able to predict response to 5-fluorouracil, and the KRAS (Kirsten rat sarcoma viral oncogene) and B-RAF (v-RAF murine sarcoma viral oncogene homolog B1) somatic gene mutation status can predict the response to anti-epidermal growth factor receptor therapy. Recent advances indicate that the widespread use of biomarkers may herald the next major advance in the diagnosis and management of CRC.
    Colorectal Disease 10/2010; 14(1):3-17. DOI:10.1111/j.1463-1318.2010.02439.x · 2.02 Impact Factor
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    ABSTRACT: The present study aimed to determine the extent of malnutrition in preoperative colorectal cancer patients. Malnutrition has been shown to affect post-operative outcome, so it would be beneficial to identify those who are malnourished or who are at risk of becoming so preoperatively. We examine whether weight loss is related to the length of stay or changes in fat free mass. Patients were enrolled consecutively from outpatients 2-4 weeks prior to surgery. Assessments included body mass index, percentage weight loss, dynamometry, Malnutrition Universal Screening Tool, Subjective Global Assessment and bioelectrical impedance. Cancer staging and hospital length of stay were recorded. One hundred and thirty-two patients were eligible and 87 enrolled. Sixty-seven patients were weight losing and 20% had lost >10% of their usual body weight. Handgrip strength was lower in malnourished patients compared to those who had not lost weight (mean 19.4 and 27.3 kg, respectively, P = 0.013). Mean (SD) fat free mass in patients with a weight loss >10% was 39.7 (13.5) kg and, in those with <10% weight loss, was 51.9 (12.0) kg (P = 0.001). This difference was not demonstrated for fat. Over half of these patients had lost weight prior to surgery and one in five were malnourished. Body composition measurements demonstrated that malnourished patients had significantly less fat free mass compared to patients who were not clinically malnourished. Nutritional screening would be beneficial in this group preoperatively to identify weight-losing patients at an early stage in the care pathway when they initially enter the secondary care system.
    Journal of Human Nutrition and Dietetics 08/2010; 23(4):402-7. DOI:10.1111/j.1365-277X.2010.01070.x · 2.07 Impact Factor
  • K Newton, J Hill
    Colorectal Disease 07/2010; 12(7):706-7. DOI:10.1111/j.1463-1318.2010.02220.x · 2.02 Impact Factor
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    ABSTRACT: Perianal Mycobacterium tuberculosis is rare, but tuberculosis (TB) is now endemic in many areas of the world. It is essential to recognize TB to institute appropriate management. We report three cases of TB presenting with supralevator abscess. We analysed the outcomes of three patients who presented to our unit, from 2004 to 2009, with supralevator abscess caused by TB. The patients presented as emergencies with symptoms of per-anal sepsis. All required multiple drainage procedures. Supralevator extension was confirmed clinically and radiologically (by magnetic resonance imaging in two patients and by computed tomography scanning in one patient). One patient was diagnosed by perianal biopsy, the second by culture of pus and the third by sputum culture. Following drainage, all three patients were given anti-TB medication for 6 months. In all patients, the fistulae had high communication with the anal canal. In one patient, local drainage and medical therapy led to sepsis resolution, the second patient has residual complex fistulae and the third patient has recently commenced antimicrobial therapy. As TB is endemic in many parts of Europe, TB should be suspected in patients with complex and/or recurrent perianal sepsis. Samples for histological and bacteriological analyses should be obtained from these patients. Recurrent perianal drainage procedures are likely to be required, and sepsis may persist after anti-TB therapy.
    Colorectal Disease 10/2009; 13(2):210-4. DOI:10.1111/j.1463-1318.2009.02093.x · 2.02 Impact Factor
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    ABSTRACT: Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.
    Clinical Genetics 03/2009; 75(2):141-9. DOI:10.1111/j.1399-0004.2008.01125.x · 3.65 Impact Factor
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    J Hill
    British Journal of Surgery 10/2008; 95(10):1195-6. DOI:10.1002/bjs.6386 · 5.21 Impact Factor