Search

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

BACKGROUND: As part of the Magnetic Resonance Imaging for Breast Screening (MARIBS), Study women with a family history of breast cancer were assessed psychologically to determine the relative psychological impact and acceptability of annual screening using magnetic resonance imaging (MRI) and conventional X-ray mammography (XRM). METHODS: Women were assessed psychologically at baseline (4 weeks before MRI and XRM), immediately before, and immediately after, both MRI and XRM, and at follow-up (6 weeks after the scans). RESULTS: Overall, both procedures were found to be acceptable with high levels of satisfaction (MRI, 96.3% and XRM, 97.7%; NS) and low levels of psychological morbidity throughout, particularly at 6-week follow-up. Low levels of self-reported distress were reported for both procedures (MRI, 13.5% and XRM, 7.8%), although MRI was more distressing (P=0.005). Similarly, higher anticipatory anxiety was reported before MRI than before XRM (P=0.003). Relative to XRM, MRI-related distress was more likely to persist at 6 weeks after the scans in the form of intrusive MRI-related thoughts (P=0.006) and total MRI-related distress (P=0.014). More women stated that they intended to return for XRM (96.3%) than for MRI (88%; P, The national study is supported by a grant from the UK Medical Research Council (G960413)

Around 30% of endometrial cancers (EC) are mismatch repair (MMR) deficient, mostly as a consequence of mutations acquired during tumorigenesis, but a significant minority is caused by Lynch syndrome (LS). This inherited cancer predisposition syndrome primes an anti-cancer immune response, even in healthy carriers. We sought to explore the intra-tumoral immunological differences between genetically confirmed LS-associated MMR-deficient (MMRd), sporadic MMR-deficient, and MMR-proficient (MMRp) EC. Endometrial tumors from women with known LS were identified (n = 25). Comparator tumors were recruited prospectively and underwent microsatellite instability (MSI) testing, immunohistochemistry (IHC) for MMR expression and MLH1 methylation testing. Those found to have MLH1 hypermethylation formed the sporadic MMR-deficient group (n = 33). Those found to be mismatch repair proficient and microsatellite stable formed the MMR-proficient group (n = 35). A fully automated monoplex IHC panel was performed on sequential formalin-fixed paraffin-embedded tumor sections to identify CD3+, CD8+, CD45RO+, FoxP3+, and PD-1+ immune cells, and PD-L1 expression by tumor/immune cells. Two independent observers quantified immune marker expression at the tumor center and invasive margin. Mean and overall compartmental T-cell counts generated standard (binary: Low/High) and higher resolution (quaternary: 0-25, 25-50, 50-75, 75-100%) immune scores, which were used as explanatory features in neural network, support vector machine, and discriminant predictive modeling. Overall T-cell counts were significantly different between the three cohorts: CD3+ (p =

Introduction Rates of contralateral risk reducing mastectomy (CRRM) are rising despite a paucity of data to support this practice. Surgeons work as part of the multidisciplinary team (MDT). They may counsel women on these requests without the benefit of established guidelines or agreed protocol. This study assessed the practices and perceptions of breast and plastic surgeons in England on CRRM. Methods A postal questionnaire was sent to 455 breast and 364 plastic surgeons practising in England. Basic demographics, trends in CRRM, risk assessment, role of the MDT and knowledge base were assessed. Results The response rate among breast surgeons was 48.3% (220/455) and 12.6% (46/364) among plastic surgeons. Nearly half (44%) of the respondents felt there had been an increase in rates of CRRM over the last three years. Seventy-one per cent of those surveyed performed 1–5 CRRMs annually while sixteen per cent did not perform this procedure at all. A third (32%) of respondents correctly quoted their patients an annual risk of 0.5–0.7%. Funding was refused in 4% of cases and 43% of the surgeons felt that in the future they would have to apply to relevant clinical commissioning groups. Over half (58%) of all respondents reported that decisions for CRRM are always discussed in the MDT meeting but 6% stated that these cases are never discussed by the MDT. BRCA mutation was perceived as the main risk factor for contralateral breast cancer by 81% of respondents. Surgeons felt that women requested CRRM mainly to alleviate anxiety. The next most common reasons were carriage of BRCA mutation and a desire to have reconstructions match. Conclusions A wide variation of surgical practices and perceptions exist in assessing women for CRRM. Guidelines to standardise practices are required.

Purpose Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS. Methods Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies. Results Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25–0.28, I2: 71%) and 0.26 (95% CI 0.25–0.27, I2: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25–0.33, I2: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses. Conclusion The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2-3% per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

Objective Lynch syndrome (LS) is an inherited tumor predisposition condition caused by mutations in the mismatch repair (MMR) genes. Mutation carriers are at increased risk of various malignancies, including ovarian cancer (OC). Relatively little is known about the pathological features and clinical behavior of LS associated OC. Methods We analyzed the data of 1047 proven MMR mutated individuals from a prospectively maintained database at a large referral center for genomic medicine in the North West of England. Data were crosschecked with pathology reports, the National Cancer Registry and death certificates, where appropriate. Data from gynecological surveillance and risk reducing surgery were analyzed. Results We identified 53 cases of LSAOC in proven MMR mutated individuals. The cumulative risk of LSAOC was 20% at age 80 in those who retained their ovaries. LSAOC presented at an earlier age (average 51, range 24–70 years) than sporadic OC. The predominant histological subtype was endometrioid adenocarcinoma (53%). Most cases presented early (85% at stage I/II vs. 15% at stage III/IV, p, Highlights • Lynch syndrome-associated ovarian cancer (LSAOC) is rare and difficult to study. • This is the largest reported series of OC from proven Lynch syndrome carriers. • Endometrioid OC was most common, followed by high grade serous, clear cell and mixed histology. • Most LSAOC was detected at stage 1 and overall 5-year survival was excellent at 80%. • Surveillance found 2 LSAOC; 3 more were diagnosed following surgery for screen-detected endometrial cancer.

Since the localization and discovery of the first high-risk breast cancer (BC) genes in 1990, there has been a substantial progress in unravelling its familial component. Increasing numbers of women at risk of BC are coming forward requesting advice on their risk and what they can do about it. Three groups of genetic predisposition alleles have so far been identified with high-risk genes conferring 40-85% lifetime risk including BRCA1, BRCA2 and TP53. Moderate risk genes (20-40% risk) including PALB1, BRIP, ATM and CHEK2, and a host of low-risk common alleles identified largely through genome-wide association studies. Currently, only BRCA1, BRCA2 and TP53 are used in clinical practice on a wide scale, although testing of up to 50-100 gene loci may be possible in the future utilizing next-generation technology.

Background: Triple-negative (TN) tumours are the predominant breast cancer subtype in BRCA1 mutation carriers. Recently, it was proposed that all individuals below 50 years of age with TN breast cancer should be offered BRCA testing. We have evaluated the BRCA1 mutation frequency and the implications for clinical practice of undertaking genetic testing in women with TN breast cancer. Methods: We undertook BRCA1 mutation analysis in 308 individuals with TN breast cancer, 159 individuals from unselected series of breast cancer and 149 individuals from series ascertained on the basis of young age and/or family history. Results: BRCA1 mutations were present in 45 out of 308 individuals. Individuals with TN cancer 10% likelihood of carrying a BRCA1 mutation in both the unselected (11 out of 58, 19%) and selected (26 out of 111, 23%) series. However, over a third would not have been offered testing using existing criteria. We estimate that testing all individuals with TN breast cancer 10% likelihood of carrying a BRCA1 mutation and are therefore eligible for testing in most centres. However, implementation may place short-term logistical and financial burdens on genetic services.

Background: Women at high ovarian cancer risk, especially those with mutations in BRCA1/BRCA2, are encouraged to undergo bilateral risk-reducing salpingo-oophorectomy (BRRSPO) prior to the natural menopause. The decision to use HRT to cover the period of oestrogen deprivation up to 50 years of age is difficult because of balancing the considerations of breast cancer risk, bone and cardiovascular health. Methods: We reviewed by questionnaire 289 women after BRRSPO aged ⩽48 years because of high ovarian cancer risk; 212 (73%) of women responded. Results: Previous HRT users (n=67) had significantly worse endocrine symptom scores than 67 current users (P=0.006). A total of 123 (58%) of women had ⩾24 months of oestrogen deprivation

Background: There are relatively few articles addressing long-term follow-up in women with breast cancer at very young ages. Methods: We have updated and extended our population-based analysis of breast cancer diagnosed at the age ⩽30 years in North-west England to include an extra 15 patients with mutation testing in BRCA1, BRCA2 and TP53, with 115 of 288 consecutive cases being tested. Kaplan–Meier curves were generated to assess overall survival, contralateral breast cancer and other second primaries. Results: Survival analysis of all 288 patients showed poor overall survival, although this improved from a 15-year survival of only 46% in those diagnosed between 1980 and 1989 to 58% in those diagnosed between 1990 and 1997 (P=0.05). Contralateral breast cancer rates were at a steady rate of 0.6 per 1000, although the rates in mutation carriers were ∼2 per 1000. Altogether, 16 BRCA1, 9 BRCA2 and 6 TP53 mutations have now been found among the 115 cases on whom DNA analysis has been performed. BRCAPRO accurately predicted the number of carriers for BRCA1 and BRCA2 and was sensitive and specific at the 10 and 20% threshold, respectively. However, BRCAPRO did not seem to give any weight to DCIS, which accounted for two BRCA1 carriers and three TP53 carriers and overpredicted mutations at the high end of the spectrum, with only 6 of 11 (54%) with a >90% probability having identifiable BRCA1/2 mutations. Interpretation: Rates of new primaries are predicted to some extent by mutation status. BRCAPRO is useful at determining those patients aged ⩽30 years to be tested.

Objective:To assess the outcome of conservative management of vestibular schwannoma.Study design:Observational study.Setting:Tertiary referral centre.Patients:Four hundred and thirty-six patients with vestibular schwannoma (490 tumours), including 327 sporadic tumours and 163 tumours in 109 patients with neurofibromatosis type two.Main outcome measures:The relationship of tumour growth to tumour size at presentation, and to certain demographic features.Results:The initial tumour size was significantly larger in the neurofibromatosis type two group (11 mm) than in the sporadic vestibular schwannoma group (5.1 mm). In both groups, 68 per cent of tumours did not grow during follow up (mean 3.6 years; range one to 14 years). The mean growth rate was 1.1 mm/year (range 0–15 mm/year) for sporadic tumours and 1.7 mm/year (range 0–18 mm/year) for neurofibromatosis type two tumours. The tumour growth rate correlated positively with tumour size in the sporadic tumour group, and correlated negatively with age in the neurofibromatosis type two group.Conclusion:Two-thirds of vestibular schwannomas did not grow. Radiological surveillance is an acceptable approach in carefully selected patients. Once a sporadic vestibular schwannoma reaches 2 cm in intracranial diameter, it is likely to continue growing. We do not recommend conservative management for sporadic tumours with an intracranial diameter of 1.5 cm or more. Vestibular schwannoma management is more complex in patients with neurofibromatosis type two.

BACKGROUND: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T > G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. METHODS: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T > G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. RESULTS: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR) = 1.01, 95% confidence interval (CI): 0.93-1.10, P(trend) = 0.77; MDM2: HR = 0.96, 95% CI: 0.84-1.09, P(trend) = 0.54) or for BRCA2 mutation carriers (TP53: HR = 0.99, 95% CI: 0.87-1.12, P(trend) = 0.83; MDM2: HR = 0.98, 95% CI: 0.80-1.21, P(trend) = 0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. CONCLUSION: There was no evidence that TP53 Arg72Pro or MDM2 309T > G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. British Journal of Cancer (2009) 101, 1456-1460. doi: 10.1038/sj.bjc.6605279 www.bjcancer.com Published online 25 August 2009 (C) 2009 Cancer Research UK

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/ genepi/boadicea/boadicea_home.html). © 2008 Cancer Research UK.

Background Rates of contralateral risk-reducing mastectomy (CRRM) are rising, despite a decreasing global incidence of contralateral breast cancer. Reasons for requesting this procedure are complex, and we have previously shown a variable practice amongst breast and plastic surgeons in England. We propose a protocol, based on a published systematic review, a national UK survey and the Manchester experience of CRRM. Methods We reviewed the literature for risk factors for contralateral breast cancer and have devised a 5-step process that includes history taking, calculating contralateral breast cancer risk, cooling off period/counselling, multi-disciplinary assessment and consent. Members of the multi-disciplinary team included the breast surgeon, plastic surgeon and geneticist, who formulated guidelines. Results A simple formula to calculate the life-time risk of contralateral breast cancer has been devised. This allows stratification of breast cancer patients into different risk-groups: low, above average, moderate and high risk. Recommendations vary according to different risk groups. Conclusion These guidelines are a useful tool for clinicians counselling women requesting CRRM. Risk assessment is mandatory in this group of patients, and our formula allows evidence-based recommendations to be made.

This paper presents the results of an investigation into tools to support blind authors in the creation and checking of word processed documents. Eighty-nine documents produced by 14 blind authors are analyzed to determine and classify common types of layout and formatting errors. Based on the survey result, two prototype tools were developed to assist blind authors in the creation of documents: a letter creation wizard, which is used before the document is produced; and a format/layout checker that detects errors and presents them to the author after the document has been created. The results of a limited evaluation of the tools by 11 blind computer users are presented. A survey of word processor usage by these users is also presented and indicates that: authors have concerns about the appearance of the documents that they produce; many blind authors fail to use word processor tools such as spell checkers, grammar checkers and templates; and a significant number of blind people rely on sighted help for document creation or checking. The paper concludes that document formatting and layout is a problem for blind authors and that tools should be able to assist.

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 individuals25 years (p0.001). 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.

Purpose Prophylactic mastectomy (PM) has proven to be the most effective method to reduce the risk of breast cancer in high-risk women. The present study aimed to present and compare the attitudes towards PM among physicians in France, Germany, the Netherlands and the United Kingdom (UK). Patients and methods An international sample of 1196 general practitioners (GPs) and 927 breast surgeons (BS) were surveyed using a mailed questionnaire. Results Only 30% of the French and 27% of the German GPs were of opinion that PM should be an option for an unaffected female BRCA1/2 mutation carrier, as compared to 85% and 92% of the GPs in the Netherlands and UK, respectively. Similarly, 78% of the French and 66% of the German BS reported a positive attitude towards PM, as compared to 100% and 97% of the BS in the Netherlands and UK, respectively. In the whole sample of GPs, a positive attitude towards PM was associated with country of residence, being female, and having more knowledge of breast/ovarian cancer genetics, while among BS there was a positive association with country of residence and having more knowledge of breast/ovarian cancer genetics as well, and, in addition, with a higher number of newly diagnosed breast cancer patients last year. Conclusion These results demonstrated the international variations in the attitude towards PM among physicians. This might reflect that different policies are adopted to prevent breast cancer in women at-risk.

To analyse the long-term outcome of translabyrinthine surgery for vestibular schwannoma (VS) in neurofibromatosis type 2 (NF2). RESEARCH TYPE: Retrospective cohort study.Two tertiary referral NF2 units.One hundred and forty eight translabyrinthine operations for patients with VS were performed. Preoperative stereotactic radiotherapy had been performed on 12(9.4%) patients.Mean tumour size was 3.1 cm. Total tumour excision was achieved in 66% of cases, capsular remnants were left in 24% of cases, and subtotal excision was achieved in 5% and partial removal was achieved in 5%. The radiological residual/recurrence rate was 13.9%. The perioperative mortality was 1.6%. At 2 years postoperatively, facial function was expressed in terms of House-Brackmann score (HB): HB 1 in 53.4%, HB 1/2 in 61.3%, HB 1-3 in 83.2% and HB 4-6 in 16.8%. All nine patients who underwent surgery following failed stereotactic radiotherapy had HB 3 function or better. Among 9.5% of the cases, 14 facial nerves were lost during surgery and repaired using direct anastomosis or grafting. There was no tinnitus present preoperatively in 27% of the cases, and 22% of patients developed tinnitus postoperatively. In patients with preoperative tinnitus, 61% remained the same, 17% got it resolved and only in 21% it worsened. The preoperative hydrocephalus rate was 26%, and among 15% of the cases five ventriculo-peritoneal (VP) shunts were performed. The cerebrospinal fluid leak rate was 2.5%. Fifty-six patients underwent auditory brainstem implantation (ABI) and two patients had cochlear implant (CI) sleepers inserted.The management of patients with NF2 presents the clinician with a formidable challenge with many patients still presenting themselves late with the neurological compromise and a large tumour load. There is still an argument for the management by observation until the neurological compromise dictates interventional treatment particularly with the option of hearing rehabilitation with ABI or CI. The translabyrinthine approach provides a very satisfactory means of reducing the overall tumour volume.

Breast cancer is not only increasing in the west but also particularly rapidly in eastern countries where traditionally the incidence has been low. The rise in incidence is mainly related to changes in reproductive patterns and lifestyle. These trends could potentially be reversed by defining women at greatest risk and offering appropriate preventive measures. A model for this approach was the establishment of Family History Clinics (FHCs), which have resulted in improved survival in younger women at high risk. New predictive models of risk that include reproductive and lifestyle factors, mammographic density and measurement of risk-associated single nucleotide polymorphisms (SNPs) may give more precise information concerning risk and enable better targeting for mammographic screening programmes and of preventive measures. Endocrine prevention using anti-oestrogens and aromatase inhibitors is effective, and observational studies suggest lifestyle modification may also be effective. However, referral to FHCs is opportunistic and predominantly includes younger women. A better approach for identifying older women at risk may be to use national breast screening programmes. Here were described pilot studies to assess whether the routine assessment of breast cancer risk is feasible within a population-based screening programme, whether the feedback and advice on risk-reducing interventions would be welcomed and taken up, and to consider whether the screening interval should be modified according to breast cancer risk.

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of “other cancers” in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1–6.0) and stomach at 2.4 (95% CI 1.2–4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9–7.8) and prostate (RR 6.3, 95% CI 4.3–9.0) and uveal melanoma (RR 99.4, 95% CI 11.1–359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9–7.8) and stomach (RR 2.7, 95% CI 1.3–4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

Background: Bilateral risk-reducing salpingo-oophorectomy (BRRSO) is the only effective way of reducing mortality from ovarian cancer. This study investigates uptake of BRRSO in 700 BRCA1/2 mutation carriers from Greater Manchester. Methods: Dates of last follow-up and BRRSO were obtained, and the following variables were investigated: ovarian cancer risk/gene, age and breast cancer history. The date of the genetic mutation report was the initiation for Kaplan–Meier analysis. Results: The uptake of BRRSO in BRCA1 mutation carriers was 54.5% (standard error 3.6%) at 5 years post testing compared with 45.5% (standard error 3.2%) in BRCA2 mutation carriers (P=0.045). The 40–59 years category showed the greatest uptake for BRRSO and uptake was significantly lower in the over 60 s (P

In 2004 the NICE guidelines on familial breast cancer advised Health Care Professionals that they should not actively seek to identify women with a family history of breast cancer. We have carried out a review of the evidence base and a large scale questionnaire survey of health professionals in four European countries. There is overwhelming support amongst GPs and surgeons against the premise that that health care professionals should not be proactive in identifying patients at risk of familial breast cancer. This that suggest the time is right to overturn the NICE decision.

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.

Background Previous publications and utilisation of risk models for BRCA1 and BRCA2 mutation identification suggests that multiple primary disease in an individual is a strong predictor of a BRCA1/2 mutation and that this is more predictive than the same cancers occurring in close relatives. Methods This study assessed the pathological mutation detection rates for BRCA1 , BRCA2 and the CHEK2c .1100 delC mutation in 2022 women with breast cancer, including 100 with breast/ovary double primary and 255 with bilateral breast cancer. Results and discussion Although detection rates for mutations in BRCA1/2 are high at 49% for breast/ovarian double primary and 34% for bilateral breast cancer, the differential effect of multiple primaries in an individual appears to have been overestimated, particularly in those families with only a few malignancies. Nonetheless, bilateral breast cancer does differentially enhance detection rates in strong familial aggregations. CHEK2 1100 DelC mutation rates were lower in bilateral than for unilateral cases at 0.8% compared to 2%. The detected mutation rates for isolated double primary breast and ovarian cancer was 14% (3/22) compared to 17% (17/99) for the same two primaries in two close relatives in families with no other cases of breast/ovarian cancer. Risk models may need to be adjusted if further studies corroborate these findings.

To identify the types and mix of technology (hardware and software) provided to post-secondary students with dyslexia under the UK's Disabled Student Allowance (DSA), and to determine the students' satisfaction with, and use of, the equipment provided and to examine their experiences with training.A telephone survey of 455 students with dyslexia who had received technology under the DSA from one equipment supplier was conducted over in the period September to December 2005. The survey obtained a mixture of quantitative data (responses to binary questions and selections from a five-point rating scale) and qualitative data (participants identifying positive and negative experiences with technology). In addition, the equipment supplier's database was used to determine the technology supplied to each of the participants.Technology provision is variable between students. The majority of students receive a recording device, text-to-speech software and concept mapping tools in addition to a standard computer system. Ninety percent of participants are satisfied or very satisfied with the hardware and the software that they receive. A total of 48.6% of participants received training, with 86.3% of those expressing satisfaction with the training they received. Of those that were offered training but elected not to receive it, the majority did so because they felt confident about their IT skills.Students express satisfaction not only with the computer systems that they receive but also with the special-purpose software provided to support their studies. Significant numbers of students elect not to receive training and may, therefore, not be using their equipment to its best advantage.

Trigeminal schwannomas are the second most common intracranial schwannoma. They may occur sporadically or in association with neurofibromatosis type 2. The vast majority are benign in nature although malignancies have been reported. They may present with a range of symptoms because of their variable locations in areas with multiple differing functional activities. There is little understanding of the natural history of these tumours, and the choice of treatment includes surgery, stereotactic radiosurgery and fractionated radiotherapy. This article reviews the management options and outcomes. The incidence of recurrence and the time interval following treatment to recurrence is unpredictable.

We report two cases of radiation-induced intracranial tumours after treatment for medulloblastoma presenting in children with nevoid basal cell carcinoma syndrome.These cases illustrate the need for judicious use of post-operative radiotherapy as secondary tumors are commonly reported. This is particularly important as the initial tumour in this cohort is of the 'less aggressive' desmoplastic subtype.

33 families with a history of male breast cancer aged 60 or less or with a family history of male and female breast cancer were screened for the presence of BRCA2 mutations. 12 pathogenic BRCA2 mutations were identified (36%) in samples from an affected family member. All mutations segregated with disease where it was possible to check. Of the 14 families fulfilling BCLC criteria, 9 (64%) had mutations whilst only 3/16 (19%) of male breast cancer patients with less significant female breast cancer family history having a mutation. All 3 families with ovarian cancer and 3 families with multiple male breast cancer cases had BRCA2 mutations. These data are a further guide to how to prioritise samples for BRCA2 mutation analysis.

The authors investigated the acceptability to women of the preventive strategies available for dealing with hereditary breast/ovarian carcinoma in France, the United Kingdom, and Canada, countries selected because of their cultural differences. The authors aimed to discover the existence of specific factors that may affect acceptability of these preventative measures.A cross-sectional, multicenter survey was conducted in Marseilles, France (n = 141), in Manchester, England (n = 130), and in Montreal, Quebec (n = 84). All of the women attending cancer genetic clinics for the first time because of a family history of breast-ovarian carcinoma completed a self-administered questionnaire before their clinic consultation.Variations in responses to different preventative options presented on the questionnaire were seen within the sample of patients considered as a whole. The highest levels of acceptability were obtained for mammographic screening (87%) and chemoprevention (58%). In contrast, prophylactic oophorectomy and prophylactic mastectomy were thought to be acceptable at an early age (before 35 years), an age associated with the highest prophylactic efficacy, by only 19% and 16% of the respondents, respectively. After multivariate adjustment, the statistical data showed that the British respondents were more in favor of oophorectomy (P0.0001) and more in favor of chemoprevention than the French (P0.001) and the Canadian respondents (P0.001). The British (overall adjusted response [OR(adj)] = 3.9; P0.001) and Canadian respondents (OR(adj) = 3; P0.01) were more in favor of prophylactic mastectomy than the French. The cumulated acceptability of mammography before the age of 40 years was found to be greater in the French (OR(adj) = 2.8; P0.01) and Canadian (OR(adj) = 3.1; P0.05) samples than in the British sample.These results demonstrated the existence of international variations in the acceptability of the preventive strategies available for women at risk for hereditary breast/ovarian carcinoma. Therefore, these results suggested that when establishing medical recommendations or planning public health interventions, physicians must integrate the population's perception of advantages and drawbacks with the patient's individual decision making.

We evaluated 99mTc-labeled anti-CD15 immunoglobulin M monoclonal antibody (LeuTech) for diagnosing acute appendicitis in patients with an equivocal clinical presentation. LeuTech avidly binds to circulating and sequestered human polymorphonuclear neutrophils in vivo, eliminating in vitro cell labeling and blood handling.We studied 49 patients to evaluate the safety and efficacy of LeuTech imaging. 99mTc-labeled LeuTech was prepared on site using a lyophilized kit, 99mTc-labeled pertechnetate, and 2 different incubation techniques, 1 at room temperature and the other at 37 degrees C. The abdomen was serially imaged for up to 3 h after the intravenous administration of 370-740 MBq 99mTc-labeled LeuTech. Scans were read as positive or negative for acute appendicitis or other intraabdominal infection. The institutional diagnosis was established by surgery, other diagnostic studies, or 1-mo clinical follow-up.Scans were positive for appendicitis in all 26 patients with appendicitis, for a sensitivity of 100%, and negative for appendicitis in 19 of 23 patients without appendicitis, for a specificity of 83%. Accuracy, positive predictive value, and negative predictive value were 92%, 87%, and 100%, respectively. Results were not different between the LeuTech preparations. The rate of laparotomies with negative findings in patients who underwent surgery was 10%. The average time from injection to LeuTech visualization in the appendix for cases positive for appendicitis was 9 min. No serious adverse reactions occurred.LeuTech imaging is safe, rapid, and sensitive for diagnosis of appendicitis in equivocal cases. The potential advantages of LeuTech over currently available radiopharmaceuticals for infection imaging are ease of preparation, absence of blood handling, excellent image quality, no requirement for SPECT, and rapid diagnostic uptake.

A family history of breast cancer has long been recognised as a significant risk factor for breast cancer. Quantifying that risk has been approached in publications and practically in a number of different ways. Increasingly regional genetics departments are called upon to help clarify guidelines for referral of women with a family history of breast cancer for genetic testing and to clarify breast cancer risk for women seeking early mammographic screening. This paper represents the current consensus guidelines from the UK Cancer Family Study Group and discusses some of the difficulties surrounding genetic risk estimation. Keywords: guidelines; genetic risk; breast cancer

The recent isolation of breast cancer predisposing genes (BRCA1 and BRCA2) allows the identification of carriers within affected families. These carriers have a 50-85% risk of developing breast or ovarian cancer and need careful follow-up. The purpose of this study was to evaluate the management and screening protocols implemented in high risk families at various family cancer clinics in Europe. A questionnaire was mailed to the members of the European Familial Breast Cancer Collaborative Group (n = 30) requesting information on the following issues: indication for surveillance of breasts and ovaries, the recommended protocol, coordination of the screening examination, prophylactic surgery, the specific management of breast cancer in a mutation carrier and the use of oestrogen. 16 centres from nine countries responded. Most centres recommend surveillance of the breasts if the lifetime risk exceeds 15-20%. The surveillance protocol that is generally advised comprises monthly self breast examination, examination by a specialist every 6 months and annual mammography, all starting from an age between 25 and 35 years. Surveillance of the ovaries is recommended in BRCA1 and BRCA2-mutation carriers, in members from breast/ovarian cancer families and in some centres in 'breast cancer only' families with an early onset of breast cancer. The recommended protocol includes gynaecological examination, sonography and estimation of CA-125 at yearly intervals starting from the age 30-35 years. Prophylactic mastectomy is considered for proven mutation carriers in some centres. Most centres consider prophylactic oophorectomy in mutation carriers and some centres also consider it for members of breast/ovarian cancer families. This survey provides insight into the guidelines for surveillance and management of familial breast cancer used at various family cancer clinics in Europe; this insight may contribute to the appropriate management of these high risk women. It should be emphasised that most recommendations are based on experts' opinion rather than on any specific studies.

Although there has been much debate about the uptake and effects of predictive testing for common cancers, such as breast and colon cancer, little has been published on the more classical tumour predisposing conditions, such as von Hippel-Lindau disease and familial adenomatous polyposis. Since 1990 the genetics departments in Manchester and Cambridge have had a genetic register for cancer predisposing syndromes and presymptomatic testing for these conditions has been offered once this has become possible. To investigate the factors that might influence uptake of genetic testing in familial cancer syndromes we have reviewed our experience. Demand for predictive testing has generally been high, but men had a lower uptake (77%) than a comparable group of women (93%) (p < 0.01).

Previous reports have indicated that 5-13 per cent of colorectal cancer is hereditary. However, the proportion of cases arising as a result of mutations in the hereditary non-polyposis colorectal cancer (HNPCC) genes remains to be determined.This study is a part prospective, part retrospective review of all cases of colorectal cancer from a district hospital over 14 years. Some 1137 consecutive patients with colorectal cancer were questioned about their family history of cancer and details were logged on a database. For the past 4 years each case has been re-evaluated where possible.Some 118 patients indicated initially that they had a first-degree relative with colorectal cancer, but on re-evaluation there were significant discrepancies. Only three cases (0.3 per cent) occurred in families which strictly fulfilled the criteria for HNPCC and there were no cases of familial adenomatous polyposis. A total of 16 patients (1.4 per cent) fulfilled looser criteria for HNPCC.This population-based study has shown a lower frequency of familial bowel cancer than previous studies and may reflect a lower incidence of inherited mutations in the HNPCC DNA mismatch repair genes than is currently accepted.

The correlations between wind velocity and suction trap catches of mosquitoes when taken at 15-min intervals during the night were studied at 2 locations. Although normal mosquito flight speeds are approximately 1 m/sec, trap catches were reduced about 50% by winds of 0.5 m/sec and 75% at 1.0 m/sec. Trap catches were inversely related to winds of all velocities and even the lightest winds reduced trap catches. No evidence was found for a threshold below which wind velocity had no effect.

It now is accepted that a small proportion of people with certain forms of cancer have a dominantly inherited gene fault that predisposes them to it. This is more likely with an early age at onset or when the person has had multiple primary tumors.Population-based data from the North West Regional Cancer Registry of England regarding 4157 ovarian cancer cases diagnosed between 1980 and 1989 were analyzed to determine the relative risks (RR) of second primary breast and colorectal carcinomas.Elevated risks approaching significance were observed for breast and colorectal carcinoma subsequent to ovarian cancer. After stratification into groups for ovarian histopathologic characteristics and age at onset, significantly elevated risks were obtained for both breast and colorectal tumors after ovarian carcinoma for women younger than 60 years of age at onset and with serous histopathologic characteristics (breast RR, 2.68, P0.05; colorectal RR, 4.25, P0.05).These results emphasize the need for greater awareness of the possibility of development of additional cancer after ovarian carcinoma in high-risk groups. Overall, the study supports the theory that breast, colorectal, and ovarian tumors are related genetically.

This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin.

A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in duodenal ulcer, gastric ulcer, and epidemic gastric cancer. The prevalence of H. pylori in any population remains unknown. We compared the prevalence of H. pylori infection in the Riyadh region of Saudia Arabia, using a specific and sensitive ELISA for IgG antibody against the high molecular weight cell-associated antigen of H. pylori (urease). Subjects were interviewed, demographic data were collected, and a serum sample was obtained. Subjects completed a questionnaire that included questions about level of education, smoking, medications used, presence and frequency of symptoms referable to the upper gastrointestinal tract, and family history of ulcer disease. We studied 557 individuals (ranging in age from 5 to 91 yr). The prevalence of H. pylori infection increased rapidly with age: from 40% of those ages 5-10 yr, to more than 70% of those 20 or older. H. pylori infection occurred with significantly more frequency in adults with less than 12 yr of schooling, compared with adults who had attended college. The high rate of acquisition of H. pylori infection in Saudia Arabia emphasizes that studies of H. pylori-disease associations must consider the baseline prevalence of H. pylori infection in that population.

An exaggerated increase in meal-stimulated gastrin is a common finding in patients with duodenal ulcer. Duodenal ulcer patients also exhibit an increase in the number of parietal cells, which results in an increase in maximum acid output. There are also data to suggest that acid hypersecretion may not predate the ulcer disease, but is acquired, possibly due to the trophic effects of the exaggerated gastrin release on parietal cells. We investigated meal-stimulated gastrin release in nine Helicobacter pylori-infected individuals; eight patients with chronic duodenal ulcer and one H. pylori-infected healthy control, both before and after therapy designed to eradicate H. pylori infection. We also simultaneously measured intragastric pH in six duodenal ulcer patients. Eradication of the H. pylori infection reversed the exaggerated meal-stimulated gastrin release (gastrin secretion fell from 141 + 16 pg/ml/h before treatment to 98 +/- 7 pg/ml/h after, p less than 0.01) without affecting intragastric pH. Whereas exaggerated meal-stimulated gastrin release may be an important pathogenetic feature of duodenal ulcer disease, we conclude that it is secondary to the H. pylori infection. This study provides further insight into the role of H. pylori in the pathogenesis of duodenal ulcer disease. We postulate that reversal of the abnormalities in gastrin secretion will be associated with a gradual return of gastric secretion to normal.

The high endogenous urease activity of Campylobacter pylori was exploited in a non-invasive test for the presence of this organism in the stomach. When 13 C-urea was administered orally after a test meal, urea-derived 13 CO 2 appeared in the respiratory CO 2 of infected individuals at a constant rate for >100 min. The test was validated in 26 individuals who underwent both the 13 C-urea breath test and endoscopic biopsy of the antral mucosa for culture and histological examination. Each positive breath test proved to be correlated with a positive culture or Warthin-Starry silver stain of a mucosal biopsy specimen, or both.

Pregnancy specific beta glycoprotein is produced by the syncytiotrophoblast and secreted into the maternal peripheral circulation reaching levels of approximately 200 m/liter in normal pregnancy at term. In the present study the distribution of this newly defined placental protein was examined in maternal and fetal compartments in 12 patients at delivery.

Colonization factor antigens (CFAs) were administered orally to volunteers, and the mucosal immune response was assessed by measuring secretory immunoglobulin A (IgA) in saliva and intestinal secretions and by challenge with virulent enterotoxigenic Escherichia coli (ETEC). A combination of CFA/I and CFA/II (8 mg each) administered orally in four doses in milk failed to induce a mucosal IgA response and also failed to protect against challenge with CFA-positive ETEC. When CFA was administered orally (1.5 mg divided into three doses with bicarbonate) to volunteers without preexisting serum anti-CFA levels, it failed to elicit a serum IgG or intestinal secretory IgA response or to protect against challenge with virulent ETEC. The CFA is destroyed by acid gastric contents but it induced significant antibody titer rises in 8 of 11 (73%) volunteers with preexisting serum anti-CFA IgG levels after oral administration of 1 mg of CFA/I with sodium bicarbonate. Subcutaneous priming (50 micrograms CFA/I) did not induce a serum IgG response but, when followed by oral boosting (1 mg CFA/I in two divided doses with sodium bicarbonate), induced intestinal anti-CFA secretory IgA in 4 of 8 volunteers and protected against challenge with CFA/I-positive ETEC. These results, although preliminary, are encouraging and demonstrate that it may be possible to develop an effective oral vaccine based on soluble nonreplicating antigens such as purified CFAs.

A 6.1 m long suction trap, with multiple air inlets located on its upwind, top, ends and downwind sides, was placed on a freely pivoting raft moored in a large borrow pit. Air inlets on the downwind side made larger captures than those on the upwind side. Inlets near the top edge of the trap captured larger numbers than those at the bottom. Larger proportions of Culex nigripalpus and Cx. erraticus accumulated behind the horizontal and vertical edges of the trap than did other species. Mosquitoes near the ends of the trap could choose whether to fly over or around the trap; most Cx. nigripalpus and Cx. erraticus flew over the trap while only Cx. pilosus favored going around the ends. Other species appeared to fly over and around the trap in approximately equal numbers. No evidence was found that flight patterns changed with differing wind velocities.

A proper perspective of the association of Campylobacter pylori with various diseases can be achieved only when the incidence of C. pylori infection in the normal population is known. We used the 13C urea breath test (a simple, specific, noninvasive, safe, and reproducible method to assess the presence of active C. pylori infection) to compare the frequency of C. pylori infection in healthy young adults from three areas of the world. We studied 26 women and 32 men (ages 20 to 29): 29 from the United States, 10 from China, 6 from Mexico, and 13 from India. All foreign nationals had been in the United States 5 years or less. The frequency of C. pylori infection was 21%, 67%, 33% and 46%, for those from the U.S., China, Mexico and India, respectively. Although, we found no difference in the frequency of C. pylori infection among ethnic groups from North America (U.S. citizens compared with citizens of Mexico), all individuals studied were of middle to upper class socioeconomic status. Subsequent studies will investigate whether the prevalence of C. pylori infection is different in economically disadvantaged populations. Our results suggest that there may be major differences in the age-related frequency of C. pylori infection in individuals from different parts of the world.