Increased risk of breast cancer among female relatives of patients with ataxia-telangiectasia: a causal relationship?

International audienc

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected

P53 germline mutations in childhood cancers and cancer risk for carrier individuals

The family history of cancer in children treated for a solid malignant tumour in the Paediatric Oncology Department at Institute Gustave-Roussy, has been investigated. In order to determine the role of germline p53 mutations in genetic predisposition to childhood cancer, germline p53 mutations were sought in individuals with at least one relative (first- or second-degree relative or first cousin) affected by any cancer before 46 years of age, or affected by multiple cancers. Screening for germline p53 mutation was possible in 268 index cases among individuals fulfilling selection criteria. Seventeen (6.3%) mutations were identified, of which 13 were inherited and four were de novo. Using maximum likelihood methods that incorporate retrospective family data and correct for ascertainment bias, the lifetime risk of cancer for mutation carriers was estimated to be 73% for males and nearly 100% for females with a high risk of breast cancer accounting for the difference. The risk of cancer associated with such mutations is very high and no evidence of low penetrance mutation was found. These mutations are frequently inherited but de novo mutations are not rare. © 2000 Cancer Research Campaig

[Could treatments with beta-blockers be associated with a reduction in cancer risk?]

BACKGROUND: The relationship between the use of anti-hypertensive drugs and cancer risk remains controversial. The main objective of this study was to assess the potential effect of beta-blocker use on cancer risk. METHODS: In a cohort of 839 patients with cardiovascular disease, followed up prospectively for an average period of 10 years, cancer occurrence was recorded according to the exposure to beta-blockers. The relative risk of cancer associated with beta-blocker use was estimated using a Cox model adjusted on gender and age. Ever- vs never-use of beta-blockers and duration of exposure to the drug were analyzed as time-dependent variables. In addition, the standardized incidence ratios (SIR) were calculated using the corresponding age- and gender-adjusted cancer incidences in the French general population. RESULTS: A total of 326 beta-blocker users and 513 users of other treatments were included in the cohort. During the follow-up period, representing 8,466 person-years, incident cancer cases were 15 and 59 in beta-blocker ever-users versus never-users, respectively. Using the Cox model, the overall relative risk of cancer was 0.51 (95% confidence interval [95% CI]: 0.29-0.90) in the beta-blocker ever-users versus never-users (p=0.02), with a 6% decrease per year of use (95% CI: 1%-12%; p=0.03). The corresponding SIR ratio between these two groups was 0.44 (95% CI: 0.24-0.76). CONCLUSION: In this cohort, the beta-blocker treatments appeared to decrease the cancer risk significantly. However, this result should be considered with caution; further work is needed, as some sources of bias associated with this type of epidemiological study cannot be totally excluded

[Could treatments with beta-blockers be associated with a reduction in cancer risk?]

BACKGROUND: The relationship between the use of anti-hypertensive drugs and cancer risk remains controversial. The main objective of this study was to assess the potential effect of beta-blocker use on cancer risk. METHODS: In a cohort of 839 patients with cardiovascular disease, followed up prospectively for an average period of 10 years, cancer occurrence was recorded according to the exposure to beta-blockers. The relative risk of cancer associated with beta-blocker use was estimated using a Cox model adjusted on gender and age. Ever- vs never-use of beta-blockers and duration of exposure to the drug were analyzed as time-dependent variables. In addition, the standardized incidence ratios (SIR) were calculated using the corresponding age- and gender-adjusted cancer incidences in the French general population. RESULTS: A total of 326 beta-blocker users and 513 users of other treatments were included in the cohort. During the follow-up period, representing 8,466 person-years, incident cancer cases were 15 and 59 in beta-blocker ever-users versus never-users, respectively. Using the Cox model, the overall relative risk of cancer was 0.51 (95% confidence interval [95% CI]: 0.29-0.90) in the beta-blocker ever-users versus never-users (p=0.02), with a 6% decrease per year of use (95% CI: 1%-12%; p=0.03). The corresponding SIR ratio between these two groups was 0.44 (95% CI: 0.24-0.76). CONCLUSION: In this cohort, the beta-blocker treatments appeared to decrease the cancer risk significantly. However, this result should be considered with caution; further work is needed, as some sources of bias associated with this type of epidemiological study cannot be totally excluded

Thyroid and Breast cancers following radiotherapy for a hemangioma during infancy

Background and purpose A cohort study was performed to investigate the carcinogenic effect of treatment with ionizing radiation of skin hemangioma in early childhood. This study presents the incidence of differentiated thyroid and breast cancers after radiotherapy in this cohort. Methods and Materials: Of a total of 8307 patients treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, 4 767 (3 317 women) were included in an incidence study, among whom 3 795 (2 698 women) received radiotherapy. External radiotherapy, Radium 226, Strontium 90, Yttrium 90, and Phosphorus 32 were used as treatment. The mean age at first exposure was 0.7 years and the mean absorbed dose to the breast was 70 mGy and 41 mGy to the thyroid. Breast and Thyroid tumors cases were obtained by sending a questionnaire, and verified from pathological reports. Estimation of breast and thyroid cancer specific incidence rates in French population was obtained from French cancer registry network. External and internal analyses were performed. Results: During an average follow-up of 35 years, a total of 11 patients developed a differentiated thyroid carcinoma and 19 women developed BC, i.e. respectively 2.5 (95%CI: 1.4-4.4) and 2.5 (95% CI 1.5-3.8) more than expected from French general population. An association between weight and BMI at age 18 and BC risk was observed. Thyroid carcinoma incidence was higher in non-smoker patients. As compared with patients who had not received radiotherapy, those who had, had a 3.5 times higher (9%CI : 2.2-5.4 ) risk of developing a BC. Despite the risk of BC was multiplied by 3.6, 6.0, 7.9, for dose of radiation to breast varying, respectively from, 0 to 10, from 10 to 100, and > 100 (mGy), as compared to patients who did not received radiotherapy, the dose response was not significant. However, a significant dose response relationship was estimated between the radiation dose received to thyroid and the risk of thyroid cancer (Excess Relative Risk per GY, ERR/Gy: 14.7, 95%CI: 1.6 - 62.9). Conclusion: This study confirms that radiation treatment performed in the past for hemangioma during infancy increased the risk of thyroid and breast cancers