Louise Olsson

Detection of proximal colorectal cancers through analysis of faecal DNA

Detection of mutations in faecal DNA represents a promising, non-invasive approach for detecting colorectal cancers in average-risk populations. One of the first practical applications of this technology involves the examination of microsatellite markers in sporadic cancers with mismatch-repair deficiencies. Since such cancers nearly always occur in the proximal colon, this test might be useful as an adjunct to sigmoidoscopy, which detects only distal colorectal lesions. We report here the first in-depth analysis of faecal DNA from patients with proximal cancers to determine the feasibility, sensitivity, and specificity of this approach. Using a sensitive method for microsatellite mutation detection, we found that 18 of 46 cancers had microsatellite alterations and that identical mutations could be identified in the faecal DNA of 17 of these 18 cases.

Family history of colorectal cancer in a Sweden county.

Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatosis polyposis (FAP) are well-known high-risk cancer syndromes. Hereditary colorectal cancer (HCRC) with at least three relatives with colorectal cancer and a dominant pattern of inheritance but with no specifications for age at onset and two close relatives with colorectal cancer (TCR) are other forms of familial clustering known to carry an increased risk of the disease. The frequency of the total burden of familial colorectal cancer is not well known. We therefore investigated the family history of 400/411 (97%) eligible patients with recently diagnosed colorectal cancer in Västmanland county, Sweden, during a 3-year period. Records or death certificates confirmed the diagnoses of relatives. Five patients (1.2%, 95% CI 0.15–2.2) were diagnosed as having HNPCC, eight (1.9%, 95% CI 0.6–3.2) as having HCRC and thirty-four (8.3%, 95% CI 5.6–11.0) were identified as having TCR. In total, 47 patients (11.4%, 95% CI 8.3–14.5) were found to have a contributing familial background. The implication is thus that every ninth patient with colorectal cancer represents a highly or intermediately increased risk of the disease among relatives. We conclude that the low frequency of individuals identified by family history alone makes the establishment of surveillance programs feasible.

Lack of an Association between the TGFBR1*6A Variant and Colorectal Cancer Risk

Purpose: Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies. Experimental Design: A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted. Results: We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A. Conclusion: Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.

Mainstreaming Gender in Multidimensional Peacekeeping: A Field Perspective

Since the Beijing Conference in 1995, mainstreaming a gender perspective in the entire work of the United Nations has been a priority. This article presents a picture of the contemporary situation concerning the mainstreaming of a gender perspective in multidimensional peacekeeping operations. The main focus concerns female participation in the field which, historically, has been very low. Research indicates that more job opportunities for women exist in operations which contain a large civilian component, but that the military and police components remain mainly male. The article also argues that human rights and humanitarian assistance are two examples of areas of multidimensional peacekeeping operations where it is vital to consider the different needs of men and women.

Gender Mainstreaming in Practice: The United Nations Transitional Assistance Group in Namibia

Gender Mainstreaming in Practice: The United Nations Transitional Assistance Group in Namibia

A population‐based audit for diagnosing colorectal cancer

Background: Knowledge of the diagnostic work‐up of colorectal cancer is a prerequisite to improve its quality. Family history is one of few known risk factors of the disease and it is therefore important to investigate to what extent this factor is used in routine management. Methods: Copies of records from all health‐care suppliers visited during diagnostic work‐up were requested for 227/235 (97%) patients with recently diagnosed colorectal cancer in the county of Västmanland during 1998–99. A first consultation was identified and records and all diagnostic measures related to the initial consultation were scrutinized. A family history of colorectal cancer was known for 179 patients. Results: Most of the patients, 107 (66%) colon and 57 (86%) rectal cancer patients, had consulted with a general practitioner. The median diagnostic work‐up time was 42 days (IQ 12–110) for colon and 23 days (IQ 0–49) for rectal cancer. A double‐contrast barium enema was the most commonly used diagnostic method for colon cancer. Family history was documented at the first consultation in 2/179 (1%) cases. In patients with right‐sided cancer, median diagnostic work‐up time was 53 days in patients with a positive result of faecal occult blood test (FOBT) as compared with 448 in patients with a negative result (P < 0.01). Conclusion: Primary care is the key actor in diagnosing rectal cancer. The restricted capacity for X‐ray is one of the main obstacles in detection of colon cancer. Family history is rarely documented during diagnostic work‐up of colorectal cancer. The benefit of using FOBT in symptomatic patients is questioned.

Advancing Gender and Peacekeeping Research

Research on gender and peacekeeping has been revolving around two strands of questions. First, what form of peace does peacekeeping contribute to establishing? And second what are the gender dimensions of how peacekeeping is implemented? Subthemes underlying these questions are concerned with whether womens participation and gender aspects of security should be integral parts of the post-war society and the effectiveness of current gender mainstreaming and balancing policies. In this commentary we argue that there has been considerable progress in the field of gender and peacekeeping. Feminist research has raised questions about the understanding and conceptualisation of peace and security, while empirical research systematically explores the gender dimensions of peacekeeping. Yet, in order for research on gender and peacekeeping to progress, it needs to address issues such as theory underdevelopment, lack of data and continued exclusion from mainstream research. The commentary highlights as an area of particular concern the failure of existing research to find common ground and outlines opportunities of building bridges between empirical and feminist researchers.

MSI Test to Distinguish between HNPCC and Other Predisposing Syndromes – of Value in Tailored Surveillance

Colorectal cancer can serve as an excellent model for cancer prevention. Tumors start as early premalignant lesions, easy to detect and remove, progress over adenoma with a varying degree of atypia into carcinomas [1]. Thus, early detection is possible and of major importance in reducing the morbidity and mortality in colorectal cancer. During the last decade much new knowledge has come to light concerning the hereditary forms of colorectal cancer. The number of individuals participating in prevention programs is increasing and includes healthy high-risk individuals [2,3]. These prevention programs comprise genetic counseling and when possible, predictive genetic testing. Regular colonoscopies provided for high-risk individuals have resulted in decreased incidence of and mortality from colorectal cancer [4]. This surveillance is well tolerated and understood by those included in these preventive programs [5].