Spotlight

Abstract

Landers et al., pp.950–956 Currently, elevated blood levels of prostate specific antigen (PSA) are used as a diagnostic marker for the early detection of prostate cancer and to follow the progress of treatment. However, serum levels are not only raised by malignant but also by benign tumors, leading to sometimes overly zealous treatment of men with benign prostate hyperplasia (BHP). In addition, up to 15% of men with PSA levels usually considered normal have prostate cancer, emphasizing the need for other and more reliable biomarkers to better assess risk. Recently, the focus has shifted from identifying single signposts to utilizing groups of known prostate cancer-specific markers to boost the reliability of individual diagnoses. In this study, the authors propose a novel gene, UDP-N-Acetyl-α-D-galactosamine transferase (GalNAc-T3), in combination with 3 other candidate genes as a reliable tool to distinguish prostate cancer from benign lesions. After sifting through collections of gene markers overexpressed in malignant prostate tissues, they picked 4 biomarkers with consistent, differential expression patterns in cancer and BHP specimens. Together, GalNAc-T3, which previously had not been associated with prostate cancer, prostate-specific membrane antigen (PSMA), Hepsin, a membrane-bound serine protease, and DD3/PCA3, a noncoding mRNA transcript, successfully spotted 100% of all adenocarcinoma samples among a group of benign prostate hyperplasia specimens without any false positives muddying the picture. These findings suggest that panels of biomarkers could eventually help pinpoint early prostate cancer and enhance diagnostic accuracy through molecular profiling. James et al., pp.969–972 The chemical composition of hair mirrors the nutritional status of the body and has been successfully used to test for mineral deficiencies, heavy metal contaminations and drug consumption. When an earlier, small-scale report by James et al. suggested that a change in the X-ray diffraction pattern of pubic hair from patients afflicted with breast cancer could diagnose the disease it was greeted with enormous interest. But others had difficulty replicating their results. Now, the authors back up their initial claim with a new, large data set and an experimental study in nude mice carrying human breast cancer xenografts. James et al. analyzed more than 500 hair samples in double-blinded breast cancer studies without identifying any false negatives. Their results indicate that the change in the diffraction pattern may even be visible before the malignancy shows up on a mammogram, as was the case in 7 women whose breast cancer diagnosis was later confirmed during a follow-up. Further, in 12 examined women who were considered cured the fiber diffraction pattern reverted to normal, except in two cases where the women were later found to have a mirror-image carcinoma. To substantiate the correlation between the observed changes with the presence of breast cancer, the authors examined whiskers removed from nude mice prior to and 8 weeks after subcutaneous implantation of the human breast cancer cell line MDA-MB-231. The diffraction pattern showed the telltale sign, a diffuse ring, soon after cell implantation and once the tumor had begun to grow. If confirmed by independent groups, these exciting results hold promise of being a user-friendly, noninvasive screening test that not only identifies the presence of breast cancer reliably and earlier than mammograms but could also confirm the success of any treatment. Boffetta et al., pp.992–995 Chewing tobacco is a major risk factor for oral and pharyngeal cancer in Asia, but it proved difficult to establish a link between mouth cancer and snus, a type of smokeless, moist tobacco widely used in the United States and Northern Europe. Consequently, in 2001 EU authorities took the regular cancer warnings off snus packaging, giving the impression that it was a healthier alternative to smoking. Now, it appears that this step may have been taken prematurely. Bofetta et al. followed a Norwegian cohort of 10,136 men enrolled in a prospective study until 2001. The participants completed a questionnaire on lifestyle habits, smoking and snus use in 1964 and 1967. About a third stuffed the small tobacco pouches under their lips. The authors found that for snus users the relative risk of pancreatic cancer increased to 1,67; that of oral and pharyngeal cancer to 1,10; that of esophageal cancer to 1,40 and that of stomach cancer to 1,11. Cancers of the lung, urinary bladder and kidney appeared unaffected. Although snuff and chewing tobacco entail very little exposure to polycyclic aromatic compounds, exposure to N-nitrosamines is substantial. This might explain the observed carcinogenicity of smokeless tobacco products in the pancreas. This study throws new light on the controversy of whether the use of smokeless tobacco products should be encouraged as a healthier alternative to smoking. Diffraction pattern of whiskers taken from the same mouse before (a) and at 8 weeks after implantation of human breast cancer cells (b). The observed diffraction change seen in the hair of women with breast cancer, the diffuse ring, is clearly visible in (b), superimposed on the normal pattern observed for mouse whiskers as seen in (a).