Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients.

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.

Dynamics of bone aluminum over one year of functioning renal graft.

The concentration of aluminum (Al) in serum, urine, and bone, as well as bone histomorphometry parameters were studied before and 1 year after kidney transplantation (Tx) in 20 dialyzed patients. One year after Tx, serum Al fell significantly from 50.3 +/- 8.8 to 23.9 +/- 2.7 micrograms/l, (53% fall). Bone Al content also decreased significantly from 62.9 +/- 9.0 to 36.5 +/- 7.0 micrograms/kg bone weight, but urine Al excretion was still above normal. The repeat bone histomorphometric examination showed a good recovery of bone resorption which correlated well with serum parathyroid hormone levels, but poorer recovery of indices of bone formation and of the extent of Al deposits in the bone as shown by aluminum staining.

Mortality from respiratory and digestive cancers among asbestos cement workers in Italy.

A cohort study is presented on the mortality of blue-collar workers in an asbestos-cement production plant that has been operating since 1907. Use of both crocidolite and chrysotile is reported. The cohort includes 2608 men and 759 women who were employed in the plant on Jan. 1, 1950 and those who started to work between 1950 and 1980. Follow-up was terminated on April 15, 1986 with 97.9% traced. Expected deaths were estimated from the age- and sex-specific regional mortality rates for the years 1969 to 1981. The data have been analyzed for the period 1964 to 1986 based on person-years at risk: 43,000 for men and 14,494 for women. A statistically significant increase was found in both sexes for mortality from all causes. From 1964 to 1986, 728 men died from all causes (608 expected), 275 with cancer at any site (158 expected) 110 with lung cancer (41 expected), 28 with pleural tumors (1 expected) and 85 with asbestosis (less than 1 expected). Corresponding figures for women were--all causes: 136 deaths versus 102 expected; all cancers: 79 verses 32 expected; lung cancer: 7 versus 2 expected; pleural tumor: 15 versus 0 expected and asbestosis: 4 versus 0 expected. Deaths from digestive tract cancer were in excess only among women (18 observed versus 10 expected, p less than 0.01). No excess was found for deaths from laryngeal cancer. Standardized mortality rates (SMR) for lung cancer among males showed a clear increase in direct relationship with length of follow-up. SMR according to length of employment were 234 for length 10 to 19 years, 363 for 20 to 29 years, and 256 for 30 years or longer (p less than 0.05 and lower).