Frigerio et al., pp. 329–338 When first diagnosed, approximately 80% of patients with primary bladder cancer present with low-grade, superficial disease, which is usually treated conservatively by transurethral resection. Although these low-grade bladder cancers have a minimal risk of progression to death, the recurrence rate reaches 70%, condemning patients to periodic and rather unpleasant cystoscopies. Unfortunately, noninvasive, cytological analysis of voided urine has proven unreliable, especially for low-grade tumors. Not surprisingly, therefore, researchers have been searching for safe, alternative screening methods, most of them based on molecular markers. Microsatellite analysis detects tumor-specific genomic alterations in cells isolated from voided urine but it is vulnerable to fluctuations in sample preparation and locus-specific amplification reproducibility. To overcome this obstacle, Frigerio et al. automated the process and determined marker-specific threshold values for loss-of-heterozygosity (LOH) to improve the sensitivity and reliability of microsatellite analysis before they tested the calibrated assay in a prospective study. When combined with conventional cytology, the new and improved LOH test could nearly triple the detection rate of the conventional cytology approach alone. When used on its own, the calibrated microsatellite assay proved to be more sensitive than a commercially available analysis by fluorescence in situ hybridization (FISH). Since over 93% of the patients with recurrent disease could be identified by a combined LOH/cytology analysis of their voided urine samples, the authors believe that most follow-up cystoscopies could be replaced by the microsatellite-based, noninvasive screening method, sparing patients the dreaded procedure without compromising on safety. Troisi et al., pp. 356–360 DES, or diethylstilbestrol, was commonly given to pregnant women in the 1940s, 1950s and 1960s to prevent spontaneous abortion and premature delivery. Several million women had already been exposed in utero before the use of DES was abruptly stopped in 1971 after research had found that the drug not only interfered with the development of the reproductive system of the fetus but also increased the risk of clear cell adenocarcinoma (CCA) of the vagina and cervix in young women. To establish whether prenatal DES exposure increases overall cancer risk, Troisi et al. combed through the DES Combined Cohort Follow-up Study, which was assembled by the National Cancer Institute in the early 1990s and represents the largest population of US individuals with documented DES exposure in utero. The authors found no increase in the overall rate of cancers when compared to the risk of the general population. However, they could not explain why their control group revealed a slightly lower risk than the general population. Comparing exposed to unexposed women, breast cancer risk was only elevated in women over 40, while the major excess risk for CCA peaked at age 25 and rapidly declined thereafter. At this point in follow-up, the authors couldn't find any convincing evidence for increased cancer risk other than CCA in young women and breast cancer in older women. Continued monitoring of DES-exposed women will be necessary to uncover any excess cancer risk that might manifest itself only later in life. Kuriki et al., pp. 377–385 Evidence accumulated in lab studies has suggested that consuming a diet rich in fish can decrease cancer risk. Fish contains high amounts of n-3 highly unsaturated fatty acids (HUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which play key roles in inhibiting cell proliferation and inducing apoptosis, respectively. In contrast to the clear-cut laboratory evidence, epidemiological studies have fallen short of demonstrating an unambiguous effect for breast cancer. In Japan, however, the country with the highest per capita consumption of fish worldwide, an inverse correlation between dietary intake of fish or n-3 HUFAs and cancer risk has been observed. But studies using appropriate biomarkers to measure n-3 HUFA intake have been missing. Hence, Kuriki et al., who recently developed a new, automated analytical method for measuring fatty acids in biomaterial, examined the relationship between fatty acid composition in erythrocytes and breast cancer risk in 103 incident cancer cases and 309 matched noncancer controls. The observed breast cancer risk showed a significant inverse association with dietary intake of n-3 HUFAs and high levels of EPA and DHA in erythrocyte membranes. Their study did not confirm the previously described association between dietary intakes of meat, total fat, saturated fatty acids (SFAs) and mono-unsaturated fatty acids (MUFAs), but did find a strong association of increased breast cancer risk with the SFA content of erythrocyte membranes, especially hexadecanoic acid, better known as palmitic acid. Further studies with larger sample sizes are now needed to uncover the mechanistic link between a diet relying heavily on fish and decreased cancer risk.
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Dec 9, 2009
John Gordon Bell + 8
Open Access
