An established hypothesis that explains the increase in risk of cancer with advancing age is centred on cell division. The older one gets, the more times one’s cells must divide (or undergo mitosis), the greater the chance that something will ‘go wrong’, thus causing a cell to become malignant. The model must be tweaked to accommodate the risk of breast cancer in women, which rises steeply between the puberty and menopause, and levels thereafter. It is thought that this is because cells in breast epithelial tissue proliferate (and then undergo cell death) each month, in response to changes of hormone levels that are part of the menstrual cycle—which takes place between puberty and menopause. So the cyclical growth of breast epithelium superimposes an additional risk over that incurred by age.
Epidemiologists Julian Peto (Institute of Cancer Research, UK) and Thomas Mack (University of Southern California) now present data that support the need for yet another tweak to the breast-cancer model (Nature Genetics, Vol. 26, Issue 4, 01 Dec 2000). It is known that women who have had breast cancer run a relatively high, constant risk (about 0.7% per year) of developing cancer in the other breast. Peto and Mack carried out a prospective study of women with breast cancer and their immediate relatives; they purposely included women with identical twins in the study. They find that the risk of an identical twin developing breast cancer is also 0.7%, regardless of age of onset of the initial breast cancer in her sister. Of course, identical twins tend to share environments (including the that of the womb), and so there may be environmental factors that confound this interpretation. But when Peto and Mack charted the risk of breast cancer in the mothers and (non-twin) sisters of index patients, they found a similar result. These women have an elevated constant risk (0.3–0.4%/year) that does not vary with age after initial diagnosis of breast cancer in the daughter/sister. The investigators interpret this to indicate that a woman’s risk of breast cancer starts from a genetically determined age, and that a high proportion of breast cancers arise in a small, susceptible group.
As Douglas Easton (of the Cancer Research Campaign) points out in an accompanying News & Views article, this model does not account for the inflection of risk seen at menopause. He suggests that overall risk of breast cancer is akin to a multi-factorial equation and that the finding of Peto and Mack may be one such factor in the equation—although cautions that epidemiological observations alone are probably too weak to provide a clear answer regarding which type of model, or mixture of models, most accurately accounts for the pattern of risk of breast cancer.
Dr. Thomas Mack
University of Southern California
Los Angeles, California
Telephone: +1 323 865 0445
Dr. Julian Peto
Institute of Cancer Research
Sutton, United Kingdom
Telephone: +44 20 8643 0424
Fax: +44 20 8770 7876
(News & Views)
Dr. Doug Easton
Strangeways Research Laboratories
Cambridge, United Kingdom
Telephone: +44 1223 740 160
Fax: +44 1223 740 159
(C) Nature Genetics press release.
Message posted by: Trevor M. D'Souza
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