© Oxford University Press 2006.
IN THIS ISSUE
H. pylori and Gastric CancerHelicobacter pylori colonization of the stomach is a risk factor for gastric adenocarcinoma. Kamangar et al. (p. 1445) conducted a prospective nested case–control study of H. pylori serology to determine the magnitude of this association. They found that H. pylori seropositivity was strongly associated with an increased risk for noncardia (lower stomach) gastric cancer but was associated with a decreased risk of cardia (upper stomach and esophagus) gastric cancer. H. pylori seropositivity rates did not vary by length of follow-up, age at diagnosis, or histologic subtype. The authors conclude that the opposing associations bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries.
In an editorial, Nyrén and Blot (p. 1432) discuss how these findings differ in some respects from those of previously published studies. They caution that gastric cancer prevention plans must consider all health outcomes that are potentially affected by H. pylori eradication.
Preterm, Underweight Children and Childhood Cancer Survivors
Childhood cancer survival rates have increased, raising questions about the possible reproductive consequences of treatment at an early age. To investigate this issue, Signorello et al. (p. 1453) examined data from more than 3,300 children born between 1968 and 2002 to survivors of childhood cancer and female siblings who participated in the Childhood Cancer Survivor Study. Children of female cancer survivors who received high-dose radiotherapy to the uterus were at higher risk of being born preterm (50.0% vs. 19.6%) or at a low birth weight (36.2% vs. 7.6%) than children of survivors who did not receive radiotherapy. The authors conclude that children of female childhood cancer survivors who undergo pelvic irradiation may be at risk from potential effects of cancer treatment, including restricted fetal growth and early birth.
In an editorial, Schover (p. 1434) discusses the findings of related studies and the mechanisms by which chemotherapy and radiotherapy may reduce fertility and increase the risk of pregnancy complications. She suggests that patient and professional education materials be designed to help female cancer survivors make informed decisions about child bearing.
New Insight into the Control of Cell Death in Cancer Cells
Cancer cells are often resistant to apoptosis, the programmed cell death that cells commit when they encounter abnormal stresses. Genetic changes that cause defects in apoptosis are sometimes detected in human tumors. Analyzing the factors that control the activation of Bax and Bak, two proteins that are critical mediators of apoptosis, Kitanaka et al. (p. 1462) observed that oxidative phosphorylation, the process by which the cell's mitochondria create useable energy in the form of ATP, was essential for Bax and Bak activation and apoptosis in cancer cells. This was true even when the cell was adequately supplied with energy by anaerobic glycolysis. The authors discuss their findings in light of often-observed preference of tumor cells for glycolysis, and they address the implications of these results for cancer therapy.
Surgical Management of Advanced Colorectal Cancer
Multivisceral resection is recommended for patients with locally advanced adherent colorectal cancer because it reduces local recurrence and improves survival. However, it may not be used in some patients because it is associated with increased morbidity compared with standard resection. Govindarajan et al. (p. 1474) examined surgical practices and outcomes among 8,380 patients in the Surveillance, Epidemiology, and End Results registry with locally advanced adherent colorectal cancer who had undergone surgical resection. They found that only one-third of the patients had received multivisceral resection and that there was considerable variation in the use of this procedure by geographic region and by patient and tumor factors. Multivisceral resection was associated with improved overall survival for both colon and rectal cancer patients compared with standard resection, and there was no associated increase in early mortality. The authors conclude that the geographic variation suggests that local organizations and care processes may play an important role in patient treatment and prognosis.
Relaxin Expression in Tumor-Targeting Adenoviruses
The success of cancer-targeting adenoviruses in gene therapy is limited by uneven viral penetration and distribution in tumors. Kim et al. (p. 1482) investigated whether adenovirus expression of the cell-matrix degradation protein relaxin could improve virus distribution and penetration in tumors. They found that relaxin expression resulted in higher viral spread in the tumor mass both in vitro and in mice, as well as in greater viral persistence and increased survival of tumor-bearing mice. Relaxin-expressing adenoviruses inhibited tumor growth and lung metastases in mice and decreased the collagen content of tumor tissue but not normal tissue. The authors conclude that relaxin expression by adenoviruses has the potential to increase the efficacy of virus-mediated cancer gene therapy.
ODC Variant, Aspirin, and Colorectal Adenomas
To test whether a polymorphism in the ornithine decarboxylase (ODC) gene may modify the effect of aspirin use on colorectal adenoma occurrence in subjects at high risk of adenoma, Barry et al. (p. 1494) analyzed data from 973 participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to receive aspirin or placebo. The authors found no overall association between genotype of the ODC polymorphism and the risk of developing new adenomas and no effect of aspirin in reducing risk among subjects homozygous for the G allele (the most common genotype). However, among subjects with at least one variant A allele who took aspirin, the authors observed reduced risks of new adenomas and advanced lesions (40.8% and 7.1%, respectively) compared with subjects who took placebo (52.9% and 14.0%, respectively). The authors conclude that the ODC genotype may modify the response to aspirin for colorectal adenoma prevention.
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