Sharon Buehler

Prolactinomas in familial multiple endocrine neoplasia syndrome type I: Relationship to HLA and carcinoid tumors

We studied four families with prolactin-secreting pituitary tumors as part of multiple endocrine neoplasia syndrome type I (MEN I). The propositus in family A had galactorrhea-amenorrhea and an enlarged sella turcica at the time of parathyroidectomy. Family studies showed that her mother had prolactinoma and primary hyper-parathyroidism, one of three uncles had primary hyperparathyroidism, and two sisters had prolactin-secreting adenomas, All affected family members shared the HLA haplotype: A1, B8, Cw-, DR3; linkage with HLA could not be excluded. The proband in family B had prolactinoma, primary hyperparathyroidism and primary hypothyroidism associated with a high-lying vestigial thyroid. The probands father had primary hyperparathyroidism and thymic carcinoid, and two uncles had primary hyperparathyroidism. The proband and father shared the haplotype A2, B8, Cw-, DR3. In family C the proband had primary hyperparathyroidism and prolactinoma. Three of her sisters had primary hyperparathyroidism. One sister, who also had carcinoid tumor of the lung and a prolactinoma, married an affected member of family D; a daughter had prolactinoma and metastatic thymic carcinoid. Both proband and sister were 46 xx/xo and shared the haplotype A1, B8, Cw-, DR3. The fourth propositus, a member of family D reputed to have familial primary hyperparathyroidism, was found to have a prolactinoma four years following parathyroidectomy. One of the patients affected uncles also had a pituitary tumor. The haplotype involved was Aw24, B35, Cw-. We conclude that (1) prolactinomas are an integral part of MEN I; (2) the syndrome may be associated with aberrant organ migration and chromosomal separation; (3) MEN I is associated with A1, B8; evidence for genetic linkage being inconclusive; (4) patients may harbor other tumors including thymic carcinoid.

Dietary patterns and colorectal cancer recurrence and survival: a cohort study

Objective To examine the association between dietary patterns and colorectal cancer (CRC) survival. Design Cohort study. Setting A familial CRC registry in Newfoundland. Participants 529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Outcome measure Participants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. Results Disease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). Conclusions The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC.

Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype

Background:Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis.Methods:A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of ‘2 years before diagnosis’ to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors.Results:Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04–3.06), but not for former (HR: 1.06; 95% CI: 0.71–1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with ⩾40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03–2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25–3.19), those who smoked ⩾30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22–2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04–1.82 and DFS: HR: 1.32; 95% CI: 1.01–1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged ⩾60: P for heterogeneity=0.03).Conclusions:Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.

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

BackgroundDiet 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.MethodsIncident 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.ResultsTotal energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, p-trend = 0.02, 5th versus 1st quintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, p-trend = 0.06, 5th versus 1st quintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, p-trend = 0.05, 5th versus 1st quintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, p-trend = 0.04, 5th versus 1st quintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk.ConclusionThis 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.

Interaction between alcohol drinking and obesity in relation to colorectal cancer risk: a case-control study in Newfoundland and Labrador, Canada

BackgroundWhile substantive epidemiological literature suggests that alcohol drinking and obesity are potential risk factors of colorectal cancer (CRC), the possible interaction between the two has not been adequately explored. We used a case-control study to examine if alcohol drinking is associated with an increased risk of CRC and if such risk differs in people with and without obesity.MethodsNewly diagnosed CRC cases were identified between 1999 and 2003 in Newfoundland and Labrador (NL). Cases were frequency-matched by age and sex with controls selected using random digit dialing. Cases (702) and controls (717) completed self-administered questionnaires assessing health and lifestyle variables. Estimates of alcohol intake included types of beverage, years of drinking, and average number of alcohol drinks per day. Odds ratios were estimated to investigate the associations of alcohol independently and when stratified by obesity status on the risk of CRC.ResultsAmong obese participants (BMI ≥ 30), alcohol was associated with higher risk of CRC (OR: 2.2; 95% CI: 1.2-4.0) relative to the non-alcohol category. Among obese individuals, 3 or more different types of drinks were associated with a 3.4-fold higher risk of CRC relative to non-drinkers. The risk of CRC also increased with drinking years and drinks daily among obese participants. However, no increased risk was observed in people without obesity.ConclusionThe effect of alcohol of drinking on CRC seems to be modified by obesity.

A randomized controlled trial of the effect of an intensive 1-year care management program on measures of health status in independent, community-living old elderly: the Eldercare project

BACKGROUND Primary care practitioners are familiar with the frail elderly and commonly have to deal with their multi-morbidity and their functional decline, both physically and mentally. However, there are well elderly with high quality of life and very few co-morbidities who seldom seek medical care. OBJECTIVE To determine if a nurse-based program of home-delivered care, linked directly with the primary care practitioner or primary care team, would improve quality of life, symptoms, satisfaction with care and utilization of community and medical services, in independent community living old elderly. DESIGN Randomized controlled trial. SETTING St. Johns, Newfoundland, Canada. PARTICIPANTS Two hundred and thirty-six independent, community-dwelling, cognitively functioning, people aged 80 years and older. INTERVENTION A nurse-based program of care, carried out in the patients home, that involved a detailed assessment of needs, the development of a plan to meet the needs, and up to eight visits to the patients home during a 1-year period to facilitate the meeting of those needs. CONTROL GROUP Usual care MAIN OUTCOME MEASUREMENTS Quality of Life measured using the SF-36 and the CASP-19 scales; symptomology using the Comorbidity Symptom Scale; patient satisfaction using the PSQ-18; and assessment of health care services (community services, emergency room visits, hospitalizations, use of diagnostic services and family doctor visits) through patient recall, family physician chart review and assessment of hospitalization records. RESULTS There were no statistical or meaningful differences between the intervention and control groups in any of the outcomes measured. CONCLUSION The intensive, home-delivered, program of care for the well old elderly did not have an impact on the outcomes measured.

Rhesus Haplotypes in Familial Hodgkin's Disease

Abstract. Previous reports of increased numbers of rhesus‐negative individuals in series of Hodgkins disease (HD) patients have received a unique type of confirmation. In an extended family of over 1,200 people in which an aggregate of 7 cases of HD has occurred, there were twice the usual number of rhesus‐negative individuals. Thus, these HD patients also arose in a population containing an excess of rhesus negatives. Detailed analysis of rhesus antigens and haplotypes with the aid of five antisera and blood samples from 1,133 community members revealed that the patients and their families carried R1 and r but that there was exclusion from those groups of Ro and ra. Ra may have been excluded from the patients but was found in members of their immediate families. No other haplotypes were identified. The differences between HD families and members of the remainder of the extended family are statistically significant (p < 0.0005). The data are consistent with two interpretations which are not mutually exclusive. First, certain rhesus complexes, notably r, may confer susceptibility to the development of HD, probably by virtue of a closely linked gene, conversely other complexes such as Ro may confer resistance. The second interpretation is that the postulated HD agent may flourish better in populations of certain rhesus make‐up than it does in others. Individuals of a particular rhesus genotype may be ‘carriers’ or ‘spreaders’. Further investigations are suggested which should contribute to the solution of this epidemiological puzzle.

An Investigation of Cancer Rates in the Argentia Region, Newfoundland and Labrador: An Ecological Study

Background. The Argentia region of Newfoundland and Labrador, Canada, was home to a US naval base during a 40-year period between the 1940s and the 1990s. Activities on the base resulted in contamination of the soil and groundwater in the region with chemicals such as heavy metals and dioxins, and residents have expressed concern about higher rates of cancer in their community. This study investigated the rate of cancer diagnosis that is disproportionately high in the Argentia region. Methods. Cases of cancer diagnosed between 1985 and 2011 were obtained for the Argentia region, two comparison communities, and the province of Newfoundland and Labrador. Crude and age-standardized incidence rates of cancer diagnosis were calculated and compared. The crude incidence rate was adjusted for differences in age demographics using census data, and age-standardized incidence rates were compared. Results. Although the Argentia region had a higher crude rate of cancer diagnosis, the age-standardized incidence rate did not differ significantly from the comparison communities or the provincial average. Argentia has an aging population, which may have influenced the perception of increased cancer diagnosis in the community. Conclusions. We did not detect an increased burden of cancer in the Argentia region.