© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 14, 1111,
July 19, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
Epidemiologic and laboratory studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) may help prevent colon cancer. Previous work had examined NSAID-induced apoptotic cell death in relation to the well-known inhibition of cyclooxygenase enzymes in colorectal cancer cells. Because NSAID-induced apoptosis can proceed independently of cyclooxygenase inhibition, however, Shureiqi et al. (p. 1136) investigated in two colorectal cancer cell lines another enzyme affected by NSAIDs, the lipoxygenase 15-LOX-1. They found that NSAIDs induced the expression and activity of 15-LOX-1, which were accompanied by apoptosis and inhibition of cell growth. Apoptosis and growth inhibition were blocked by the addition of caffeic acid and restored by 13-S-HODE, a metabolic product of the enzyme. The authors conclude that increased expression of 15-LOX-1 is crucial to NSAID-induced apoptosis and may represent a key step in chemoprevention of colon cancer by NSAIDs.
Risk of Leukemia Following Testicular Cancer
Men with testicular cancer are at an increased risk of leukemia, but the relationship between this risk and previous cancer treatment is not well characterized. In a case–control study, Travis et al. (p. 1165) describe risk estimates for leukemia following radiotherapy and chemotherapy treatment regimens for testicular cancer among patients diagnosed with testicular cancer from 1970 through 1993. Past treatments for testicular cancer were associated with an increased risk of leukemia, with evidence for dose–response relationships for both radiotherapy to active bone marrow and cisplatin-based chemotherapy. Statistically nonsignificant excesses were estimated for current radiotherapy regimens limited to the abdomen and pelvis. The authors conclude by noting that the survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.
"While physicians should be reminded of the possible late toxicity of treatment of testicular cancer . . . , the relatively low excess risk of leukemia is reassuring."
—Travis et al.
Hepatocellular Carcinoma and Familial Risk
In certain parts of the developing world, hepatocellular carcinoma (HCC)—the most common form of liver cancer—is a major public health problem. Infection with hepatitis B virus (HBV) is one of the most important risk factors for the disease, and family history may play a role as well. Yu et al. (p. 1159) examined the contribution of familial predisposition to risk of HCC in a cohort in Taiwan of HBV carriers and their relatives. They found that first-degree relatives of HBV carriers with HCC are at increased risk of HCC themselves; this increase in risk was particularly striking in siblings. Increased rates of liver cirrhosis were also seen in case families. Although the gene responsible for the observed results is not yet known, the authors suggest that screening programs for HCC should consider paying special attention to relatives of HCC patients.
In an accompanying editorial, Petersen (p. 1114) notes that this study provides important new information to support the concept of genetic susceptibility in hepatocellular carcinoma but adds that more work needs to be done before there will be clinical or public health impact.
Breast-Conserving Therapy and Mastectomy
Breast-conserving therapy (lumpectomy followed by radiation) is known to be as effective as mastectomy in the treatment of stage I breast cancer. To investigate whether the two treatments are as effective, over the long term, in the treatment of larger tumors, van Dongen et al. (p. 1143) conducted a randomized clinical trial of 868 women, most of whom had tumors of 2.1 to 5 cm. The women were assigned to receive either breast-conserving therapy or mastectomy and were followed for a median of 13.4 years. The authors found that the overall survival rates and incidence of distant disease 10 years after treatment were similar in the two treatment arms. Although women who received breast-conserving therapy had a higher incidence of locoregional recurrence after 10 years (20%) than women who received mastectomy (12%), the authors note that the incidence of locoregional recurrence is still small relative to that of distant recurrence.
Multiple Births and Ovarian Cancer
Prevailing hypotheses about the causes of ovarian cancer predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of ovarian cancer, but some evidence suggests that they may actually be at a lower risk. To resolve this issue, Whiteman et al. (p. 1172) analyzed pooled data from eight case–control studies of parous women and ovarian cancer. Overall, they found that women with ovarian cancer were no more likely to have a history of multiple births compared with other women. When the patients were separated according to the histologic subtype of their cancer, they found heterogeneous associations across studies for mucinous ovarian cancers but found reduced risks of nonmucinous ovarian cancer among women with a history of multiple births.
Population Stratification and Quantification of Bias
Critics have argued that bias from population stratification (the mixture of individuals from heterogeneous genetic backgrounds) undermines the credibility of epidemiologic studies designed to estimate the association between a genotype and the disease risk. Wacholder et al. (p. 1151) measured such bias by estimating the effect of the genetic factor on risk of disease with and without adjustment for ethnicity. Using data on the frequency of the N-acetyltransferase (NAT2) slow acetylation genotype (which may increase cancer risk) and incidence rates of male bladder and female breast cancers in eight European countries, they concluded that the bias from a study consisting of a mixture of non-Hispanic U.S. Caucasians with the same NAT2 frequencies and cancer rates as in their ancestral country is likely to be below 1%. Also, from an evaluation of a wide range of genotype frequencies and cancer rates, they found bias below 10% except in extreme situations.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||