© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 22, 1787,
November 15, 2000
© 2000 Oxford University Press
IN THIS ISSUE |
Studies on the association between smoking and colon cancer have not consistently found a link. However, there may be subtypes of colon tumors for which smoking is biologically relevant. Slattery et al. (p. 1831) examined molecular aspects of colon tumors from subjects in a case–control study. They looked particularly at microsatellite instability (MSI), a pathologic feature of some colon tumors in which alterations are found in short nucleotide repeated DNA sequences. They also collected data on lifestyle factors of study subjects using questionnaires. MSI, found in 17% of colon tumors in this study, was associated with current cigarette smoking as well as with history of 35 or more years of smoking and with smoking at least a pack a day. Other factors, such as body mass, were less consistently associated with MSI. The authors estimate that smoking may account for approximately 21% of MSI in colon tumors.
In an accompanying editorial, Neugut and Terry (p. 1791) discuss the results of Slattery et al. in the context of different causal pathways for colon cancer. Such pathways, they say, appear to be defined by distinctive patterns of co-occurring, cancer-related genetic lesions, such as MSI and K-ras mutations; each pattern is in turn associated with different colon cancer risk factors. Neugut and Terry note that this phenomenon could explain why associations between cigarette smoking and colon cancer have not been consistently observed.
"The observed associations . . . provide information that can be valuable in describing disease pathways and the role that nongenetic factors play in those pathways."
—Slattery et al.
Hypermethylation in the APC Gene and Esophageal Cancer
Esophageal cancer is a deadly malignancy with a poor prognosis. The adenomatous polyposis coli (APC) gene shows frequent loss of heterozygosity in esophageal carcinomas, but inactivating mutations in this gene are rarely found in their tumors. Kawakami et al. (p. 1805) investigated whether the APC promoter region is hypermethylated, which could silence the gene, and whether this abnormality could serve as a prognostic plasma biomarker in patients with esophageal carcinoma. They observed APC gene hypermethylation in 92% of 52 esophageal adenocarcinomas, 50% of 32 esophageal squamous cell carcinomas, and 39.5% of 43 Barrett’s metaplasias studied, but not in matching normal tissues. In esophageal adenocarcinoma patients, there was a statistically significant association between high plasma levels of methylated APC DNA and reduced patient survival. The authors suggest that plasma levels of hypermethylated APC DNA may constitute a potentially useful biomarker of biologically aggressive disease.
Fruits and Vegetables and Lung Cancer Incidence
Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer in several studies. Feskanich et al. (p. 1812) examined the association between lung cancer and fruit and vegetable consumption in prospective cohorts of 77 283 women in the Nurses’ Health Study and 47 778 men in the Health Professionals’ Follow-up Study. They found that total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among women but not among men. After adjusting for smoking-related variables, they noted that the age-adjusted protective effect of fruits and vegetables was substantially attenuated in women and was eliminated in men. Total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, but the reduction was not statistically significant. The researchers indicate a need for further characterization of this association in relation to the disease.
"Although the ‘5 A Day’ Program promotes a reasonable and prudent diet . . . , it is necessary to continue the evaluation of these recommendations in terms of specific health outcomes."
—Feskanich et al.
HAART Therapy for AIDS and Reduction in Cancer Incidence
Highly active antiretroviral therapy (HAART) has been widely used in people infected with human immunodeficiency virus-1 (HIV) in North America, Europe, and Australia since 1997. AIDS incidence and mortality rates have fallen since HAART came into widespread use; however, HAART’s impact on cancer incidence in HIV-infected people is unknown. A group of investigators working under the International Collaboration on HIV and Cancer (p. 1823) collectively analyzed data from 23 prospective studies, comparing cancer incidence rates in the periods before (1992 through 1996) and after (1997 through 1999) the widespread use of HAART. They noted substantial reductions in the incidence of Kaposi’s sarcoma and non-Hodgkin’s lymphoma, the risk of which is considerably increased in people infected with HIV. There was no substantial change in the incidence of other cancers.
Vitamin D5 and Prevention of Rat Mammary Carcinogenesis
Although the active form of vitamin D is a potent cell-differentiating agent, its use in cancer prevention or therapy is precluded because it induces excessive blood calcium levels (hypercalcemia). Mehta et al. (p. 1836) synthesized an analogue of vitamin D5, that is less calcemic than the active form of vitamin D. They determined the efficacy of this compound at two different levels (25 µg/kg diet and 50 µg/kg diet) in an animal model. This analogue, 1
-hydroxyvitamin D5, reduced the tumor incidence from 80% in control rats to 53.3% and 46.6%, respectively, in the two treatment groups. The tumor multiplicity was reduced from 1.6 tumors per rat to 1.2 and 0.8, respectively. The vitamin D5 analogue was effective during both the initiation and the promotion stages of mouse mammary lesion formation in organ culture. The authors conclude that 1-hydroxyvitamin D5 reduces the incidence of mammary carcinogenesis in vivo, and they recommend its further development as a chemopreventive agent.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||