Penetrance of colorectal cancer among MLH1/MSH2 carriers participating in the colorectal cancer familial registry in Ontario

<p>Abstract</p> <p>Background</p> <p>Several DNA mismatch repair (MMR) genes, responsible for the majority of Lynch Syndrome cancers, have been identified, predominantly <it>MLH1 </it>and <it>MSH2</it>, but the risk associated with these mutations is still not well established. The aim of this study is to provide population-based estimates of the risks of colorectal cancer (CRC) by gender and mutation type from the Ontario population.</p> <p>Methods</p> <p>We analyzed 32 families segregating MMR mutations selected from the Ontario Familial Colorectal Cancer Registry and including 199 first-degree and 421 second-degree relatives. The cumulative risks were estimated using a modified segregation-based approach, which allows correction for the ascertainment of the Lynch Syndrome families and permits account to be taken for missing genotype information.</p> <p>Results</p> <p>The risks of developing CRC by age 70 were 60% and 47% among men and women carriers of any MMR mutation, respectively. Among <it>MLH1 </it>mutation carriers, males had significantly higher risks than females at all ages (67% vs. 35% by age 70, p-value = 0.02), while the risks were similar in <it>MSH2 </it>carriers (about 54%). The relative risk associated with <it>MLH1 </it>was almost constant with age (hazard ratio (HR) varied between 5.5-5.1 over age 30–70), while the HR for <it>MSH2 </it>decreased with age (from 13.1 at age 30 to 5.4 at age 70).</p> <p>Conclusion</p> <p>This study provides a unique population-based study of CRC risks among <it>MSH2</it>/<it>MLH1 </it>mutation carriers in a Canadian population and can help to better define and understand the patterns of risks among members of Lynch Syndrome families.</p

Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study

BACKGROUND: While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. METHODS: We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol. RESULTS: No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. CONCLUSIONS: This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population

Hygiene inspections on passenger ships in Europe - an overview

<p>Abstract</p> <p>Background</p> <p>Hygiene inspections on passenger ships are important for the prevention of communicable diseases. The European Union (EU) countries conduct hygiene inspections on passenger ships in order to ensure that appropriate measures have been taken to eliminate potential sources of contamination which could lead to the spread of communicable diseases. This study was implemented within the framework of the EU SHIPSAN project and it investigates the legislation applied and practices of hygiene inspections of passenger ships in the EU Member States (MS) and European Free Trade Association countries.</p> <p>Methods</p> <p>Two questionnaires were composed and disseminated to 28 countries. A total of 92 questionnaires were completed by competent authorities responsible for hygiene inspections (n = 48) and the creation of legislation (n = 44); response rates were 96%, and 75.9%, respectively.</p> <p>Results</p> <p>Out of the 48 responding authorities responsible for hygiene inspections, a routine programme was used by 19 (39.6%) of these to conduct inspections of ships on national voyages and by 26 (54.2%) for ships on international voyages. Standardised inspection forms are used by 59.1% of the authorities. A scoring inspection system is applied by five (11.6%) of the 43 responding authorities. Environmental sampling is conducted by 84.1% of the authorities (37 out of 44). The inspection results are collected and analysed by 54.5% (24 out of 44) of the authorities, while 9 authorities (20.5%) declared that they publish the results. Inspections are conducted during outbreak investigations by 75% and 70.8% of the authorities, on ships on national and international voyages, respectively. A total of 31 (64.6%) and 39 (81.3%) authorities conducted inspections during complaint investigations on ships on international and on national voyages, respectively. Port-to-port communication between the national port authorities was reported by 35.4% (17 out of 48) of the responding authorities and 20.8% (10 out of 48) of the port authorities of other countries.</p> <p>Conclusion</p> <p>This study revealed a diversity of approaches and practices in the conduct of inspections, differences in the qualifications/knowledge/experience of inspectors, the legislation applied during inspections, and the lack of communication and training among many EU countries. An integrated European inspection programme involving competent expert inspectors in each EU Member States and special training for ship hygiene delivered to crew members and inspectors would help to minimize the risk of communicable diseases. Common inspection tools at a European level for hygiene inspection practices and port-to-port communication are needed.</p

Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies

INTRODUCTION: Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER(+)PR(+ )and ER(-)PR(- )cancer risk. MATERIALS AND METHODS: We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model. RESULTS: Each birth reduced the risk of ER(+)PR(+ )cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER(+)PR(+ )cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER(-)PR(- )cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER(+)PR(+ )than ER(-)PR(- )cancer (RR = 0.72 for ER(+)PR(+ )cancer; RR = 0.84 for ER(-)PR(- )cancer, p for homogeneity = 0.006). CONCLUSION: Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth

Dietary isoflavone and the risk of colorectal adenoma: a case–control study in Japan

We conducted a case–control study in a Japanese population to investigate the association between dietary isoflavone intake and the risk of colorectal adenoma. Participants who underwent magnifying colonoscopy with dye spreading as part of a cancer screening programme responded to a self-administered questionnaire, which included lifestyle information and intake of 145 food items, before the colonoscopy. A total of 721 case and 697 control subjects were enrolled. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. We found a significant inverse association between dietary isoflavone intake and the risk of colorectal adenoma in men and women combined. However, the inverse association was not linear; rather, all quartiles above the first showed a similar decrease in risk, with multivariable-adjusted ORs and 95% CIs compared with the lowest quartile of 0.77 (0.57–1.04), 0.76 (0.56–1.02) and 0.70 (0.51–0.96) in the second, third and highest quartiles, respectively (P for trend=0.03). Of interest, the observed association was more prominent in women than in men. The observed ceiling effect associated with higher isoflavone intake suggests that a lower intake of dietary isoflavone might be associated with an increased risk of colorectal adenoma in Japanese populations

Association of total energy intake and macronutrient consumption with colorectal cancer risk: results from a large population-based case-control study in Newfoundland and Labrador and Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada.</p> <p>Methods</p> <p>Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk.</p> <p>Results</p> <p>Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, <it>p</it>-trend = 0.02, 5^thversus 1^stquintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, <it>p</it>-trend = 0.06, 5^thversus 1^stquintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, <it>p</it>-trend = 0.05, 5^thversus 1^stquintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, <it>p</it>-trend = 0.04, 5^thversus 1^stquintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk.</p> <p>Conclusion</p> <p>This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.</p

Germline EPHB2 Receptor Variants in Familial Colorectal Cancer

Familial clustering of colorectal cancer occurs in 15–20% of cases, however recognized cancer syndromes explain only a small fraction of this disease. Thus, the genetic basis for the majority of hereditary colorectal cancer remains unknown. EPHB2 has recently been implicated as a candidate tumor suppressor gene in colorectal cancer. The aim of this study was to evaluate the contribution of EPHB2 to hereditary colorectal cancer. We screened for germline EPHB2 sequence variants in 116 population-based familial colorectal cancer cases by DNA sequencing. We then estimated the population frequencies and characterized the biological activities of the EPHB2 variants identified. Three novel nonsynonymous missense alterations were detected. Two of these variants (A438T and G787R) result in significant residue changes, while the third leads to a conservative substitution in the carboxy-terminal SAM domain (V945I). The former two variants were found once in the 116 cases, while the V945I variant was present in 2 cases. Genotyping of additional patients with colorectal cancer and control subjects revealed that A438T and G787R represent rare EPHB2 alleles. In vitro functional studies show that the G787R substitution, located in the kinase domain, causes impaired receptor kinase activity and is therefore pathogenic, whereas the A438T variant retains its receptor function and likely represents a neutral polymorphism. Tumor tissue from the G787R variant case manifested loss of heterozygosity, with loss of the wild-type allele, supporting a tumor suppressor role for EPHB2 in rare colorectal cancer cases. Rare germline EPHB2 variants may contribute to a small fraction of hereditary colorectal cancer

Use of antidepressant medications in relation to the incidence of breast cancer

Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case–control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N=2904) and five controls were selected for each case (N=14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio=1.06, 95% CI 0.94–1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR=0.98, 95% CI 0.80–1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants

Lack of Association of SULT1A1 R213H Polymorphism with Colorectal Cancer: A Meta-Analysis

BACKGROUND: A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC. METHODS AND FINDINGS: Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94-1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74-1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77-1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92-1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91-1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73-1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75-1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90-1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95-1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93-1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78-1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83-1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92-1.13, P = 0.75). CONCLUSION: This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC