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Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence. Image 1 • Glycidol animal cancer test data were evaluated with a multiplicative risk model. • In vivo dosimetry of glycidol improved the estimation of the cancer risk coefficient. • A relative cancer risk coefficient for glycidol common for rat and mouse was derived. • The relative risk coefficient was approximately the same for responding tumor sites. • The relative risk coefficient was extrapolated to human exposure levels. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients have a high incidence of cutaneous squamous cell carcinoma and often develop multiple and aggressive tumours. This retrospective study based on the Swedish organ transplant cohort, focuses on the deaths caused by cutaneous squamous cell carcinoma and aims to elucidate the clinicopathological features of these tumours. The cohort comprised 5931 patients who underwent organ transplantation during the period 1970 to 1997 and were registered in the Swedish In-patient Registry, Cancer Registry and Causes-of-Death Registry. A total of 544 cutaneous squamous cell carcinomas in 201 patients were re-examined. The dominating size of the tumours was 5-10 mm and one-third of the tumours were removed by methods other than excision surgery. Well-differentiated tumours and Clark level IV were predominant. Seven patients died from their tumours, all of which were localized on the head. The principal site of metastasis was the parotid gland. The mean duration between date of transplantation and death was 10.4 years (range 6-17 years). Mortality from cutaneous cell carcinoma was compared with that of the general population. There was a highly increased risk; standardized mortality ratio 52.2; 95% confidence interval 21.0-107.6. However, the mortality rate in the Swedish cohort appears to be lower than what has been reported previously from other countries. [ABSTRACT FROM AUTHOR]

Context During pregnancy, serum levels of estrogen, progesterone, and other hormones are markedly higher than during other periods of life. Pregnancy hormones primarily are produced in the placenta, and signs of placental impairment may serve as indirect markers of hormone exposures during pregnancy. During pregnancy, these markers have been inconsistently associated with subsequent risk of breast cancer in the mother. Objective To examine associations between indirect markers of hormonal exposures, such as placental weight and other pregnancy characteristics, and maternal risk of developing breast cancer. Design and Setting Population-based cohort study using data from the Swedish Birth Register, the Swedish Cancer Register, the Swedish Cause of Death Register, and the Swedish Register of Population and Population Changes. Participants Women included in the Sweden Birth Register who delivered singletons between 1982 and 1989, with complete information on date of birth and gestational age. Women were followed up until the occurrence of breast cancer, death, or end of follow-up (December 31, 2001). Cox proportional hazards models were used to estimate associations between hormone exposures and risks of breast cancer. Main Outcome Measure Incidence of invasive breast cancer. Results Of 314 019 women in the cohort, 2216 (0.7%) developed breast cancer during the follow-up through 2001, of whom 2100 (95%) were diagnosed before age 50 years. Compared with women who had placentas weighing less than 500 g in 2 consecutive pregnancies, the risk of breast cancer was increased among women whose placentas weighed between 500 and 699 g in their first pregnancy and at least 700 g in their second pregnancy (or vice versa) (adjusted hazard ratio, 1.82; 95% confidence interval [CI], 1.07-3.08), and the corresponding risk was doubled among women whose placentas weighed at least 700 g in both pregnancies (adjusted hazard ratio, 2.05; 95% CI, 1.15-3.64). A high birth weight (≥4000 g) in 2 successive births was associated with an increased risk of breast cancer before but not after adjusting for placental weight and other covariates (adjusted hazard ratio, 1.10; 95% CI, 0.76-1.59). Conclusions Placental weight is positively associated with maternal risk of breast cancer. These results further support the hypothesis that pregnancy hormones are important modifiers of subsequent maternal breast cancer risk. [ABSTRACT FROM AUTHOR]

Organ transplant recipients are frequently affected by skin cancer, which might also be a major cause of long-term mortality. Excessive sun exposure is considered to be a factor in the aetiology, but uncertainty about the importance of this and other proposed risk factors remains. The purpose of this study was to investigate sun behaviour before and/or after the transplantation in kidney transplant recipients with or without cutaneous squamous cell carcinoma. A nested, population-based, case-control study was carried out on 95 kidney transplant recipients who had contracted cutaneous squamous cell carcinoma after the transplantation and on an accurately matched control population of 154 kidney transplanted patients. Information on sun exposure before and after the transplantation, skin type, use of sunbeds, warts, etc., was obtained from a questionnaire which contained 38 detailed questions. The differences between cases and control subjects were not significant for sun exposure before or after the transplantation, sun protective measures, number of sunburns, outdoor occupation, smoking habits or use of sunbeds. Compared to patients with skin type IV, the cutaneous squamous cell carcinoma odds ratio was 3.0 (95% CI=1.3-7.0) for skin type I+II. Patients with light blond or red hair colour also had a higher odds ratio than those with dark hair, 3.2 (95% CI=1.2-8.2), and patients with warts after the transplantation had a higher odds ratio than those without, 2.2 (95% CI=1.2-4.2). In conclusion, poor tanning ability rather than the amount of sun exposure is associated with the development of cutaneous squamous cell carcinoma in kidney transplant recipients and warts appearing after the transplantation indicate increased risk. [ABSTRACT FROM AUTHOR]

Development of malignant tumours in chronic burn wounds or scars is extremely rare, but a frequently reported complication. Most of these tumours are squamous cell carcinoma and, more occasionally, basal cell carcinoma and malignant melanoma are reported. The interval between the initial burn and the diagnosis of the tumour is usually long; 20-30 years or more. A large number of case reports and small series of selected patients have been published. Only one epidemiological study has been performed recently, but it could not confirm any increased risk. We conducted a historical co-hort study to assess the risk of cancer in Swedish patients with burn injuries. Using the national Inpatient Registry we identified 37,095 patients who had been hospitalized for burn injuries. This cohort was linked with the Swedish Cancer Registry for a virtually complete follow-up with regard to cancer. The mean follow-up time was 16.4 years (range >0-3 9). The risk of developing any form of cancer was slightly increased: standardized incidence ratio (SIR) 1.11 (95% confidence interval (CI) 1.06-1.16) based on 2227 patients with cancer. However, squamous cell carcinoma: SIR 0.88 (95% CI 0.70-1.09) and malignant melanoma: SIR 0.88 (95% CI 0.68-1.12) did not occur more often than expected. Also, in a subgroup of 12,783 patients who were followed for 20-39 years, no in- creased risk of skin cancer could be detected. This study does not support any casual association between burn injuries and a later risk of skin cancer. [ABSTRACT FROM AUTHOR]