Spotlight

Abstract

Watson et al., pp. 6–10 Growing experimental and clinical evidence supports the existence of a functional cancer immunosurveillance process in vivo acting as a cancer suppressor. For various tumor types, including colorectal cancer, it has been noted that many tumors lose or downregulate cell surface expression of MHC class I molecules, with a resulting resistance to cytotoxic T cell-mediated attack. However, no study has systematically analyzed MHC class I expression and attempted to correlate levels with tumor prognosis. In this issue of the IJC, Watson and colleagues report on the study of 450 colorectal cancers. MHC class I expression levels were analyzed in these tumors and correlated with prognosis. Tumors characterized by either high or no MHC class I expression were associated with similar disease-specific survival times. The authors hypothesize that this is probably because loss of MHC class I expression is associated with the specific recognition and killing of tumor cells by NK cells. In contrast, they observe that tumors expressing low levels of class I MHC proteins conferred a significantly poorer prognosis. These new results indicate that low level expression of MHC class I proteins could be used as a prognostic marker and could guide the selection of unique immunomodulatory approaches in the treatment of colorectal cancer. Tanaka et al., pp. 25–34 Inflammation has recently emerged as a contributing factor in the development of various cancers, including colorectal cancer. The mouse model for familial adenomatous polyposis, ApcMin/+, contains a truncating mutation of the Apc gene. These mice spontaneously develop numerous adenomas of the small intestine. To test the possible effect of inflammation as a contributor to colorectal development in this model, Tanaka and colleagues treated these mice, or control mice, with dextran sodium sulfate (DSS). At week 5 after administration, numerous colonic neoplasms developed in ApcMin/+ but not Apc+/+ mice. The treatment was also associated with an increase in the number of small intestinal polyps. These observations indicate a strong promotion effect in the intestinal carcinogenesis of ApcMin/+ mice and are consistent with observations in patients with inflammatory bowel disease, where a strong association between chronic inflammation and cancer development has long been noted. Nkondjock et al., pp. 103–107 Caffeinated coffee is the world's most popular stimulant. While the unwanted effects of coffee consumption are widely recognized, less is known about its potential health benefits. Coffee is an important source of phytoestrogens and enhances the levels of circulating sex hormone binding globulin, thus decreasing the bioavailability of estrogen. Its effect on breast cancer remains controversial. However, some studies have linked coffee consumption with a low risk for breast cancer development. Nkondjock and colleagues have looked at the coffee drinking habits of women with mutations in the BRCA1 and 2 genes. These women carry a high lifetime risk (80%) for breast cancer. The authors report that BRCA mutation carriers who consumed at least 6 cups of coffee per day had a statistically significant reduction in breast cancer risk, relative to carriers who never drank coffee. Importantly, this protective effect was restricted to caffeinated coffee. One possibility is that CYP1A2, an enzyme involved in the 2-hydroxylation of estradiol, is upregulated by caffeine, increasing the ratio of 2-hydroxyestrone (OHE) to 16α-OHE in coffee drinkers. Such an increase has been associated with a low risk of breast cancer in the past. If this indeed is the mechanism of action, the protective effect of replacing coffee with a dietary supplement (such as diindolymethane, DIM), which upregulates CYP activity, should now be investigated. Chan et al., pp. 243–245 The etiologic role of human papillomavirus (HPV) in cervical cancer is well established. From the more than 100 HPV types, at least 30 have been associated with cervical cancer. HPV detection and subtyping relies on PCR amplification. GP5+/6+ and MY09/My11 are the most commonly used primers. A third primer pair (PGMY09/11) was later introduced. In their study, Chan and colleagues compared the three primer pairs in a study of 120 cervical cancer samples isolated from Hong Kong Chinese women. Of these, 119 samples were positive for HPV DNA by at least one of the three primer combinations. The most common HPV types were HPV16 (50%), 18 (21.7%), 52 (12.5%), 58 (8.3%) and 33 (5%). The use of PGMY09/11 primers proved most sensitive, with an overall positive detection rate of 84.2%. In contrast, the GP5+/6+ primers failed to identify any of the HPV52-positive samples. This misrepresentation was particularly striking since a substantial portion (40%) of the HPV52 infections represented coinfections with so-called high-risk types. The authors caution against relying on the HPV detection system with GP5+/6+ primers as this might lead to a biased assessment of the risk associated with certain HPV types and an underestimation of coinfections.