© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 11, 899,
June 2, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Human T-cell leukemia virus (HTLV) and bovine leukemia virus (BLV) are retroviruses that cause hematopoietic cancers and encode a unique protein, Tax, which is involved in the transformation of infected cells. Philpott and Buehring (p. 933) have investigated the mechanism by which Tax proteins may induce cell transformation. They observed chromosomal damage and diminished DNA integrity in both virus-infected and tax gene-transfected cells. To ascertain which pathways of DNA repair might be inhibited, the investigators evaluated the repair of selective DNA lesions introduced by specific agents. HTLV- or BLV-infected or tax gene-transfected cells showed normal ability to repair DNA damage induced by deoxyribonuclease I or psoralen but markedly decreased ability to repair damage induced by UV light, quercetin, or hydrogen peroxide. These results suggest that base-excision repair of oxidative damage is the pathway most inhibited by Tax proteins. This inhibition may contribute to the virus-initiated mechanism(s) of cell transformation.
BRCA1 and BRCA2 Mutations in Early-Onset Breast Cancer
Mutations in the BRCA1 and BRCA2 genes have been found in most families with cases of both breast and ovarian cancers or with many cases of early-onset breast cancer. Until now, however, no determination had been made of the prevalence of mutations in these genes in an outbred population unselected for a family history of breast cancer. In this issue, Peto et al. (p. 943) report results from a study in Britain involving two population-based series of young patients with breast cancer. They found that mutations in the BRCA1 and the BRCA2 genes contributed approximately equally to early-onset breast cancer in these women and that such mutations appear to account for only a small proportion of the familial risk of breast cancer in this outbred population.
"Only a small proportion of patients with early-onset breast cancer carry a mutation in one or the other gene, and only a small proportion of the familial risk of breast cancer is attributable to these genes."
—Peto et al.
In an editorial, Burke et al. (p. 904) state that the findings of Peto et al. provide new information about the complexity of breast cancer genetics and about the importance of modifying factors (environmental, behavioral, and genetic) on inherited cancer risk. The editorialists conclude that the study documents a pattern likely to be repeated in other cancers: Genes will be identified through linkage studies using the highest risk families, and, thus, risk associated with mutations in these genes will initially be overestimated.
Prostaglandin E2 Levels in Rectal Mucosa
Physical inactivity and a higher body mass index (BMI) have consistently been shown to increase the risk of colon cancer, and evidence suggests a relationship between prostaglandin levels in the colonic mucosa and risk of this cancer. In view of these data, Martínez et al. (p. 950) have investigated whether higher levels of leisure-time physical activity or a lower BMI are associated with lower concentrations of prostaglandin E2 (PGE2) in rectal mucosa. After adjustment for age, a higher BMI was found to be associated with higher PGE2 levels. In addition, a higher level of leisure-time physical activity was found to be inversely related to rectal mucosal PGE2 level. The authors conclude that physical activity and obesity may alter the risk of colon cancer through their effects on PGE2 synthesis.
HPV and Risk of Cervical Lesions
Human papillomavirus (HPV) infection has consistently been associated with cervical carcinoma and its cytologic precursors, cervical squamous intraepithelial lesions (SIL). Liaw et al. (p. 954) conducted a prospective nested case-control study of the risk of developing SIL in cytologically normal women who had no history of cervical neoplasia. Compared with women who initially tested negative for HPV DNA, women who tested positive for HPV DNA in cervical lavages at study enrollment were 3.8 times more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely to develop high-grade SIL. HPV 16 was the virus type most predictive of SIL. The authors conclude that the findings support a causal relationship between HPV and cervical cancer.
"The strong association between enrollment HPV infection and subsequent incident cervical squamous intraepithelial lesions...supports the hypothesis that HPV infection is the primary cause of cervical neoplasia."
—Liaw et al.
Colorectal Cancer
Potter (p. 916) presents a comprehensive review of the literature on colorectal cancer, with particular emphasis on the relationship between epidemiology and molecular biology. Many important molecular pathways, as well as environmental exposures, that might lead to colorectal cancer have been covered in detail. The author thinks that understanding environmental exposures and host susceptibilities in relation to molecular pathways has implications for screening, treatment, surveillance, and prevention.
Androgen Receptor Polymorphism and Breast Cancer Risk
Spurdle et al. (p. 961) have conducted a population-based, case-control-family study to determine whether the polymorphic CAG repeat length in exon 1 of the androgen receptor gene is a risk factor for early-onset breast cancer in the Australian population. Case subjects under 40 years of age at diagnosis with a first primary breast cancer and age-matched control subjects were interviewed to assess family history and other risk factors; androgen receptor CAG repeat length was measured in both groups. The authors report that, whether analyzed as a continuous or a dichotomous variable, there was no association between CAG repeat length and breast cancer risk, before or after adjustment for risk factors, despite having an 80% power to detect modest effects.
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