© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 15, 1263,
August 4, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Alterations in microsatellite sequences within human DNA, either in the form of microsatellite instability or allelic imbalances involving specific chromosome regions, are commonly found in cells from colorectal cancers. Halling et al. (p. 1295) sought to determine whether the presence or absence of such genetic alterations could allow clinicians to separate patients with Astler-Coller stage B2 or C colorectal cancer into groups with favorable or unfavorable prognoses. The researchers examined fixed sections from 508 tumors obtained from 2887 patients participating in any of seven clinical trials of adjuvant chemotherapy. A high frequency of microsatellite instability (i.e., in more than 30% of the chromosomal loci examined) was associated with statistically significant improvements in survival and time to disease recurrence. In contrast, allelic imbalance involving chromosome 8p was associated with statistically significant decreases in survival and time to recurrence—an association that appears not to have been reported previously.
In an accompanying editorial, Nicholl and Dunlop (p. 1267) urge the confirmation of the findings of Halling et al. in a large, prospective cohort of patients given the same adjuvant treatment. The editorialists catalog the suspected tumor suppressor genes located on human chromosome 8p. They also discuss the relationship between microsatellite instability, defects in DNA mismatch repair, and patient survival.
Sun Exposure and Sunscreen Use
Exposure to sunshine is associated with increased risk of melanoma and basal cell skin cancer. Use of sunscreen can help prevent sunburn, but uncertainty exists with regard to its ability to protect against damage from solar radiation. Furthermore, it may actually prolong the duration of sun exposure. Autier et al. (p. 1304) tested this hypothesis by randomly assigning young European volunteers to receive unmarked tubes of stronger or weaker sunscreen before their summer vacations and asked them to record details of daily activities during which they were exposed to the sun. Baseline characteristics (e.g., skin complexion), mean vacation lengths, and the amounts of sunscreen used were similar between the two groups. The researchers found that participants who used the stronger sunscreen stayed in the sun longer than those using the weaker sunscreen and started sunbathing earlier in the day (encompassing more hours of peak sunlight) over the course of their holidays.
". . . participants who used the stronger sunscreen stayed in the sun longer than those using the weaker sunscreen."
—Autier et al.
In an editorial, Emmons and Colditz (p. 1269) further discuss the findings of Autier et al. They stress the need in the United States for policies at both the local and national levels—similar to effective programs established in Australia—to prevent excess sun exposure, particularly among children.
Cancer Risk in BRCA2 Gene Mutation Carriers
Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. Easton, Thompson, and their collaborators in the Breast Cancer Linkage Consortium (p. 1310) investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America. They observed statistically significant increases in risks for cancers of the prostate, pancreas, gallbladder, and stomach and for malignant melanoma. The relative risk of prostate cancer for men below the age of 65 years was 7.33. Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and of ovarian cancer by age 70 years were estimated to be 52.3% and 15.9%, respectively.
Retinoid Receptors and Chemoprevention
Retinoids, such as 13-cis-retinoic acid (13-cis-RA), can be useful in reversing neoplastic lesions and in preventing the development of second primary cancers in the upper aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In addition, suppression of RARß expression has been demonstrated in lung cancer cells. Xu et al. (p. 1317) examined expression of RARß messenger RNA in bronchial biopsy specimens from heavy smokers without lung cancer before (at baseline) and after 6 months of treatment with 13-cis-RA or placebo. A statistically significant decrease in aberrant expression of RARß (i.e., at least one of six biopsy specimens lacking receptor expression) was observed at 6 months in the subjects who received retinoic acid treatment compared with subjects who received placebo. The researchers conclude that RARß expression may prove useful in monitoring the effects of 13-cis-RA in chemoprevention trials.
Telomerase and Differentiation State of Cancer Cells
Telomerase is an enzyme responsible for maintaining the length of telomeres (ends of chromosomes) during cell division. This enzyme is repressed in normal, differentiated cells but is active in cancer cells. It has been reported that telomerase activity becomes repressed in tumor cell lines that undergo induced differentiation. To investigate the relationship between telomerase activity and tumor cell differentiation state further, Albanell et al. (p. 1321) studied germ cell cancers, which contain high telomerase activity and are capable of differentiating into mature teratomas. Telomerase activity was detected in all germ cell tumors examined but not in any mature teratoma, supporting an inverse relationship between telomerase activation and tumor cell differentiation state. The authors conclude that the absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas.
". . . this study offers evidence for a direct link between telomerase activation and differentiation state of clinical germ cell tumors."
—Albanell et al.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||