Cancer mortality during the 1968-1994 period in a mining area in France.

We performed a geographical analysis of cancer mortality in the communes surrounding an industrial mining complex (Salsigne, France) where suspicious levels of pollution due to arsenic were measured. Compared with that observed in a control area, we showed a significant excess of mortality due to all cancer types (ratio of standard mortality ratios (ratio of SMRs)=1.1), lung cancer (ratio of SMRs=1.8), pharynx cancer (ratio of SMRs=2.1) in the whole population, and due to digestive system cancer (ratio of SMRs=1.3) among women. The results were similar after controlling for the occupation distribution in the populations. Excluding mining complex workers deaths from the deaths in the studied populations did not modify the pattern of our results. We concluded that the excess of cancer deaths could not be exclusively due to potential professional exposures among the workers of the mining complex and are probably explained by environmental contamination.

[Could treatments with beta-blockers be associated with a reduction in cancer risk?]. / Les traitements par beta-bloquants pourraient-ils être associés à une diminution du risque de cancer?

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.

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.

Possible relationship between the van der Woude syndrome (vWS) locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P).

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans occurring with a birth prevalence of approximately 1:1,000. CL/P may be part of a defined syndrome, sequence or association, although most individual or familial cases present as an isolated (nonsyndromic) malformation (NSCL/P). Inheritance is generally regarded as multigenic although, in some families, NSCL/P seemingly segregates as a monogenic trait. On the other hand, van der Woude syndrome (vWS) is a rare autosomal dominant with cardinal features of lower-lip pits (LLP) and CL/P or cleft palate (alone). Since none of these traits is present in all mutation carriers, some individual or familial vWS cases, especially those lacking LLP, are indiscernible from NSCL/P, raising the question whether allelic variation at the vWS locus could underlie NSCL/P. This question was addressed using parametric linkage (LOD score) analysis in 21 multiplex NSCL/P families based on a tightly linked microsatellite marker (D1S3753), and nonparametric analysis using the transmission/disequilibrium test (GTDT) in 106 NSCL/P triads and selecting markers D1S205, D1S491, and D1S3753. No evidence for linkage of NSCL/P to vWS was found on the 21 families using the LOD score approach. In contrast, TDT yielded a significant P value of 0.04 for D1S205, supporting involvement of vWS in NSCL/P in a complex, modifying/polygenic manner rather than as a monogenic/major disease locus.

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.