© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 18, 1455,
September 20, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
Although mammography screening for breast cancer among women 50 years of age and older has been shown in several studies to reduce breast cancer deaths compared with no screening, the incremental effect of mammography screening over and above physical examination of the breasts is not known. Miller et al. (p. 1490), in a breast screening study in Canada, compared 39,405 women randomly assigned to receive either annual mammographic screening plus physical examination of the breasts or annual physical examination alone. All women were taught breast self-examination one-to-one by trained personnel. More breast cancers were detected in the group receiving mammography, but breast cancer deaths were equal in the two groups. These findings, after an average follow-up of 13 years, confirm early results from the same trial. The authors suggest that physical breast examination, combined with competent breast self-examination, may be an alternative to mammographic screening in women aged 50 years and older.
"The Canadian National Breast Screening Study-2 is the only trial that has evaluated the effect of mammography over and above physical examination of the breasts and breast self-examination in women aged 50–59 years."
—Miller et al.
Prevalence of Hereditary Nonpolyposis Colon Cancer
Colon cancer is one of the most common forms of cancer in the United States, but it is not clear how much of the disease is an inherited form called hereditary nonpolyposis colon cancer, or HNPCC. Peel et al. (p. 1517) addressed this question by examining a population-based cohort of colon cancer cases in three counties of southern California. They based their ascertainment of HNPCC on incidence of colon cancer in first- and second-degree relatives. They collected additional data from patients with both sporadic and familial colon cancer and analyzed mismatch repair genes, finding a lower prevalence of mutations than in previous research. They estimated that, in their population, the prevalence of HNPCC among persons diagnosed with colon cancer was about 1%, a lower figure than estimated in other studies.
Hypermethylation of the DAP Kinase Promoter and Lung Cancer
Hypermethylation of the promoter for death-associated protein (DAP) kinase, an enzyme that is involved in programmed cell death, represses the expression of DAP kinase and is a common abnormality in early-stage non-small-cell lung cancer (NSCLC). Tang et al. (p. 1511) investigated whether the hypermethylation status of the DAP kinase promoter influences the prognosis of patients with NSCLC. In 135 patients with early-stage NSCLC, 59 had tumors with hypermethylated DAP kinase promoters. These patients had a statistically significantly poorer probability of overall survival 5 years after surgery than those without hypermethylation. In addition, the probability of 5-year disease-specific survival was strikingly better for patients without hypermethylation than for those with hypermethylation. The authors conclude that hypermethylation of the DAP kinase promoter is strongly associated with survival and that DAP kinase plays an important role in determining the biologic aggressiveness of early-stage NSCLC.
In an accompanying editorial, Baylin et al. (p. 1460) consider the wider implications of epigenetic changes such as the hypermethylation of gene promoters both for understanding the mechanisms that drive tumorigenesis and as a molecular marker for the early detection of some cancers.
"Multivariate analysis indicated that hypermethylation of the DAP kinase promoter is the only independent predictor for disease-specific survival among clinical and histologic parameters tested."
—Tang et al.
HPV-Associated Malignancies in HIV Infection and AIDS
Human papillomavirus (HPV)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Frisch et al. (p. 1500) investigated whether the high frequency of these cancers is due to lifestyle factors associated with both HPV and HIV infections or to HIV-induced immunosuppression. They studied in situ and invasive HPV-associated cancers, and they observed that all HPV-associated cancers in patients with HIV infection/AIDS occurred in excess compared with numbers expected in the general population. Increasing relative risks for in situ cancers to and beyond the time of AIDS onset, the authors conclude, may reflect the gradual loss of control over HPV-infected keratinocytes with advancing immunosuppression. They also note that the lack of a similar increase for invasive cancers suggests that late-stage cancer invasion is not greatly influenced by immune status.
Risk of Hodgkin’s Disease After Infectious Mononucleosis
Infectious mononucleosis is caused by the Epstein-Barr virus and has been known to be associated with an increased risk for Hodgkin’s disease. However, little is known about how infectious mononucleosis affects the long-term risk of Hodgkin’s disease or any other cancer, how this risk varies with age at infectious mononucleosis diagnosis, and how the risk for Hodgkin’s disease varies in different age groups. Hjalgrim et al. (p. 1522) followed population-based cohorts of patients with infectious mononucleosis in Denmark and Sweden for cancer occurrence. They found that, in addition to Hodgkin’s disease, only skin cancers occurred in statistically significant excess. The risk for Hodgkin’s disease remained elevated for up to two decades after the occurrence of infectious mononucleosis but decreased with time. Following infectious mononucleosis, the risk for Hodgkin’s disease was particularly increased at ages 15–34 years—more than three times higher than during any other age period.
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