Carcinoma cancer risk assessment

The following example is based on a risk assessment of di(2-ethylhexyl) phthalate (DEHP) performed by Arthur D. Little. The experimental dose-response data upon which the extrapolation is based are presented in Table II. DEHP was shown to produce a statistically significant increase in hepatocellular carcinoma when added to the diet of laboratory mice (14). Equivalent human doses were calculated using the methods described earlier, and the response was then extrapolated downward using each of the three models selected. The results of this extrapolation are shown in Table III for a range of human exposure levels from ten micrograms to one hundred milligrams per day. The risk is expressed as the number of excess lifetime cancers expected per million exposed population. 

Summary Primary hepatocellular carcinoma is one of the most common cancers in the world and is prevalent on the continents of Africa and Asia. A number of classical epidemiological studies have determined that the exposure status of people to aflatoxin B1 is an important risk factor in the etiology of liver cancer. However, these studies have only relied upon the criteria of presumptive intake data, rather than information obtained from quantitative analyses of food samples, biological fluids and from people exposed to aflatoxin. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of aflatoxin B1 in people, thereby facilitating risk assessments. Preliminary data, reported here, support the concept that measurement of the major, rapidly excised AFB-N7-Gua adduct in urine and quantification of the more persistent aflatoxin albumin adduct are appropriate dosimeters for estimating exposure status and possibly risk in individuals consuming this mycotoxin. 

When assessing the risk of endometrial malignancy in women with breast cancer taking tamoxifen, it is worth taking into account evidence that patients with breast cancer may at the outset have some endometrial pathology. In women with breast cancer scheduled for tamoxifen there were endometrial polyps in 9.3%, endometrial cysts in 16%, and synechiae in 12% at the outset. Tamoxifen significantly increased the incidence of these benign endometrial lesions, usually after less than 1 year of treatment. There were no cases of endometrial carcinoma in 34 patients who had taken tamoxifen for 12-24 months, and only one in 78 patients who had taken it for 5-72 months (103). 

Tumorigenicity The risks of endometrial cancer and ovarian cancer in women who have used perineal talcum have been reported [66. The effects of perineal use of talcum powder have been assessed in nurses. About 40% of women who responded to questions about perineal use of talcum reported ever use. The analysis included 66 028 women and there were 599 incident cases of invasive endometrial carcinoma. There was no association overall, but when the results were analysed according to menopausal status there was a positive association in post-menopausal women ever use of talcum powder was associated with a 21% increase in risk of endometrial cancer, and regular use (at least once a week) was associated with a 245-fold increase in risk. There was a borderline increase in risk with increasing frequency of use. 

Tumorigenjdty Previous studies have suggested an association between the use of hair dyes and some cancers [SEDA-15, 1573 SEDA-30, 182, SEDA-31, 288]. Hair dyes are among the chemicals most extensively used and they contain aromatic amine deri-vates, many of which are mutagenic, and which are associated with a risk of basal cell carcinoma. In a cohort study of hairdressers, there was an increased risk of in situ skin cancers. In this case-control study, patients with basal cell carcinomas on the head and neck were matched with controls to assess the relation with the use of hair dyes [22 ]. Patients without a history of known susceptibility factors for basal cell carcinoma were asked about the details of their use of hair dyes. Of 100 women with basal cell carcinomas, 64 had used hair dyes, compared with 54 of 117 controls. The patients with basal cell carcinomas also tended to use darker hair dyes and used dyes more frequently than those without basal cell carcinomas. 

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