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Background: The French health authorities are considering expanding the current selective hepatitis E virus (HEV)-RNA testing procedure to include all donations in order to further reduce transfusion-transmitted HEV infection. Data obtained from blood donors (BDs) tested for HEV-RNA between 2015 and 2021 were used to assess the most efficient nucleic acid testing (NAT) strategy., Materials and Methods: Viral loads (VLs) and the plasma volume of blood components, as well as an HEV-RNA dose of 3.85 log IU as the infectious threshold and an assay with a 95% limit of detection (LOD) at 17 IU/mL, were used to assess the proportion of: (i) HEV-RNA-positive BDs that would remain undetected; and (ii) blood components associated with these undetected BDs with an HEV-RNA dose >3.85 log IU, considering 4 NAT options (Individual testing [ID], MP-6, MP-12, and MP-24)., Results: Of the 510,118 BDs collected during the study period, 510 (0.10%) were HEV-RNA-positive. Based on measurable VLs available in 388 cases, 1%, 15.2%, 21.8%, and 32.6% of BDs would theoretically pass undetected due to a VL below the LOD of ID, MP-6, MP-12, and MP-24 testing, respectively. All BDs associated with a potentially infectious blood component would be detected with ID-NAT while 13% of them would be undetected with MP-6, 19.6% with MP-12, and 30.4% with MP-24 depending on the plasma volume. No red blood cell (RBC) components with an HEV-RNA dose >3.85 log IU would enter the blood supply, regardless of the NAT strategy used., Discussion: A highly sensitive ID-NAT would ensure maximum safety. However, an MP-based strategy can be considered given that: (i) the risk of transmission is closely related to the plasma volume of blood components; (ii) RBC are the most commonly transfused components and have a low plasma content; and (iii) HEV-RNA doses transmitting infection exceed 4 log IU. To minimise the potential risk associated with apheresis platelet components and fresh frozen plasma, less than 12 donations should be pooled using an NAT assay with a LOD of approximately 20 IU/mL.

In case of suspected hereditary predisposition to digestive cancers, next-generation sequencing can analyze simultaneously several genes associated with an increased risk of developing these tumors. Thus, "Gastro Intestinal" (GI) gene panels are commonly used in French molecular genetic laboratories. Lack of international recommendations led to disparities in the composition of these panels and in the management of patients. To harmonize practices, the Genetics and Cancer Group (GGC)-Unicancer set up a working group who carried out a review of the literature for 31 genes of interest in this context and established a list of genes for which the estimated risks associated with pathogenic variant seemed sufficiently reliable and high for clinical use. Pancreatic cancer susceptibility genes have been excluded. This expertise defined a panel of 14 genes of confirmed clinical interest and relevant for genetic counseling: APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The reasons for the exclusion of the others 23 genes have been discussed. The paucity of estimates of the associated tumor risks led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their implication in the molecular pathways involved in the pathophysiology of GI cancers. A regular update of the literature is planned to up-grade this panel of genes in case of new data on candidate genes. Genetic and epidemiological studies and international collaborations are needed to better estimate the risks associated with the pathogenic variants of these genes either selected or not in the current panel., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This work is part of a global project aiming to use medico-administrative big data from the whole French agricultural population (~3 millions), collected through their mandatory health insurance system (Mutualité Sociale Agricole), to highlight associations between chronic diseases and agricultural activities. At the request of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), our objective was to estimate which pesticides were probably used by each agricultural worker, in order to include this information in our analyses and search for association with diseases. We selected five databases to achieve this objective: the Graphical Land Parcel Registration (RPG), the French Agricultural Census, "Cultivation Practice" surveys from the Agriculture ministry, the MATPHYTO crop-exposure matrix and the Compilation of Phytosanitary Indexes from the French Public Health Agency. A geographical grid was designed to use geographical location while maintaining worker anonymity, dividing France into square tracts of variable surface each containing a minimum of 1500 agricultural workers. We developed an automated algorithm to predict each individual potential exposure by crossing her/his occupational activity, the geographical grid and the RPG to deduce cultivation practices and use it as a gateway to estimate pesticides use. This approach allowed drawing, from administrative data, a list of substances potentially used by each agricultural worker throughout France. Results of the algorithm are illustrated at collective level (descriptive statistics for the whole population), as well as at individual level (some workers taken as examples). The generalization of this method in other national contexts is discussed. By linking this information with the health insurance databases, this approach could contribute to the agricultural workers health surveillance.

Familial adenomatous polyposis (FAP) is a rare autosomal-inherited disease that highly predisposes to colorectal cancer, characterized by a diffuse duodenal and colorectal polyposis associated with various extradigestive tumors and linked to germline mutations within the APC gene. A French consortium of laboratories involved in APC mutation screening has progressively improved the description of the variation spectrum, inferred functional significance of nontruncating variations, and delineated phenotypic characteristics of the disease. The current version of the UMD-APC database is described here. The total number of variations has risen to 5,453 representing 1,473 distinct variations. The published records initially registered into the database were extended with 3,581 germline variations found through genetic testing performed by the eight licensed laboratories belonging to the French APC network. Sixty six of 149 variations of previously unknown significance have now been classified as (likely) causal or neutral. The database is available on the Internet (http://www.umd.be/APC/) and updated twice per year according to the consensus rules of the network. The UMD-APC database is thus expected to facilitate functional classification of rare synonymous, nonsynonymous, and intronic mutations and consequently improve genetic counseling and medical care in FAP families., (© 2014 WILEY PERIODICALS, INC.)

Although the connection between diet, lifestyle and hormones suggests that nutritional and lifestyle factors may exert an influence in the etiology of breast cancer, it is not clear whether these factors operate in the same way in women without BRCA gene mutations. A nested case-control study was conducted in a cohort of French-Canadian women, with 560 members involving 280 nongene carriers of mutated BRCA gene affected by breast cancer and 280 nonaffected and nongene carriers of mutated BRCA gene. A validated semi-quantitative food frequency questionnaire was used to ascertain dietary intake, and a core questionnaire, to gather information on lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models. It was found that energy intake >2,057 Kcal/day was significantly and positively related to breast cancer risk (OR = 2.54; 95% CI: 1.67-3.84; p = 0.01). Women who drank more than eight cups of coffee per day had an increased risk of breast cancer: OR = 1.40 (95% CI: 1.09-2.24; p = 0.03). Subjects who drank >9 g of alcohol (ethanol) per day had an increased risk of breast cancer: OR = 1.55 (95% CI: 1.02-2.37; p = 0.04). In addition, a positive and significant association was noted between the consumption of beer, wine and spirits, and breast cancer risk. The ORs were 1.34 (95% CI: 1.28-2.11; p = 0.04) for more than two bottles of beer per week, OR = 1.16 (95% CI: 1.08-2.58; p = 0.05) for >10 oz of wine per week and OR = 1.09 (95% CI: 1.02-2.08; p = 0.05) for >6 oz of spirit per week, respectively. Intakes of other nutrients and dietary components were not significantly associated with nongene carrier breast cancer risk. This study provides evidence that total energy intake, coffee, and alcohol consumption may play a role in breast cancer risk.

Background: The TP53 polymorphisms Arg72Pro (Ex4+199 G>C) and Ins16 (IVS3+24 ins16) have been proposed to modify risk of breast cancer associated with germline BRCA1 and BRCA2 mutations. Allele frequencies of these polymorphisms were investigated to determine if they modify risk in BRCA mutation carriers in breast cancer cases drawn from French Canadian cancer families, a population shown to exhibit strong founder effects., Methods: The frequencies of the TP53 alleles, genotypes and haplotypes of 157 index breast cancer cases comprised of 42 BRCA1 mutation carriers, 57 BRCA2 mutation carriers, and 58 BRCA mutation-negative cases, where each case was drawn from independently ascertained families were compared. The effect of TP53 variants on the age of diagnosis was also investigated for these groups. The TP53 polymorphisms were also investigated in 112 women of French Canadian descent with no personal history of cancer., Results: The BRCA mutation-positive groups had the highest frequency of homozygous carriers of the 72Pro allele compared with mutation-negative group. The TP53 polymorphisms exhibited linkage disequilibrium (p < 0.001), where the 72Arg and Ins16minus alleles occurred in strong disequilibrium. The highest frequency of carriers of Ins16minus-72Arg haplotype occurred in the BRCA mutation-negative groups. The BRCA1 mutation carriers homozygous for the 72Pro allele had the youngest ages of diagnosis of breast cancer. However none of these observations were statistically significant. In contrast, the BRCA2 mutation carriers homozygous for the 72Pro allele had a significantly older age of diagnosis of breast cancer (p = 0.018). Moreover, in this group, the mean age of diagnosis of breast cancer in carriers of the Ins16minus-72Arg haplotype was significantly younger than that of the individuals who did not this carry this haplotype (p = 0.009)., Conclusion: We observed no significant association of breast cancer risk with TP53 genetic variants based on BRCA1/2 mutation carrier status. Although the small sample size did not permit analysis of all possible haplotypes, we observed that BRCA2 mutation carriers harboring the Ins16minus-72Arg haplotype had a significantly younger mean age of diagnosis of breast cancer. These observations suggest that investigations in a larger French Canadian sample are warranted to further elucidate the effects of TP53 variants on age of diagnosis of breast cancer among BRCA1 and BRCA2 mutation carriers.

Strong inter- and intrafamilial variation of penetrance of breast and ovarian cancer is observed in BRCA1 mutation carriers. The wild-type copy of the BRCA1 gene is a plausible candidate as a cancer risk modifier given that the residual function corresponding to the intact BRCA1 allele may influence the process of tumor formation in BRCA1 carriers. Indeed, growing evidence is now becoming available on impaired reparation of double-strand DNA breaks in cells heterozygous for BRCA1 mutations, implying an enhanced mutability of BRCA1(+/-) cells. To determine whether certain variant forms of the wild-type BRCA1 allele are implicated in variation of the BRCA1-related cancer risk, their effect was studied in a panel of 591 women with BRCA1 germ-line mutations. We found that BRCA1 carriers with the wild-type BRCA1 copy bearing a common Gly1038 variant were at increased risk of ovarian cancer (hazards ratio, 1.50; 95% confidence interval, 1.03-2.19). The results of our study imply that a quite significant proportion of the interindividual variability in ovarian cancer penetrance in BRCA1 carriers may be explained by a common BRCA1 Gly1038 wild-type allele, given its high frequency (0.27).

The aim of this study was to investigate the effects of cancer genetic consultations on feelings of anxiety in women with breast/ovarian cancer. Among the 138 women attending six French clinics during a one-year period, 115 (83.3%) answered pre- and post-consultation questionnaires. The state anxiety score (Spielberger's STAI) was lower (paired t-test, p<0.001) after the consultation (34.7 9.4) than before (38.8 10.5). The time elapsing since cancer diagnosis (r=-0.28, p=0.007) was the main predictor of the decrease in anxiety. The patients consulting earlier after their cancer was diagnosed were more anxious before the consultation than those consulting later: whereas their anxiety states after the consultation were similar. The consultation effectively decreased the anxiety observed and the anxiety felt by cancer patients before the consultation may constitute an anticipatory stress response that should be investigated.

Before the organisation of breast cancer predictive testing in France, consultands' attitudes towards this kind of testing and towards passing on information about the family cancer risk to their relatives were investigated. This survey was carried out from January 1994 to January 1995 at six specialised cancer genetic clinics located in different parts of France Female consultands who were first degree relatives of cancer patients and who had at least one case of breast cancer in their family, affecting either themselves or a first degree relative or both, participated in this study. Among the 248 eligible consultands attending the clinics during the study period, 84.3% answered a post-consultation questionnaire. Among the 209 respondents, 40.7% (n = 85) were cancer patients and 59.3% (n = 124) were healthy consultands. A high consensus in favour of genetic testing was noted, since 87.7% of the sample stated that they would ask for breast cancer gene testing if this test became available. The underlying assumption of 96.6% of the women was that their health surveillance would be improved after a positive test. A high awareness of the anxiety that would be generated in a family after a positive result was observed and found to be associated (p < 0.05) with the anxiety and depressive profiles of the patients. Half of the healthy respondents said they would not change their attitude towards screening if the results of predictive testing turned out to be negative. Only 13.7% of the 161 patients who stated that the oncogeneticists asked them to contact their relatives firmly refused to do so, mainly because of difficult family relationships.

The aim of this study was to determine in healthy consultees attending cancer genetics clinics their risk status, their pathways leading to the clinics, their expectations and perception of cancer risk. In 1994, the consultees at six French centres completed a questionnaire before their first oncogenetic consultation. The oncogeneticists subsequently filled in a standardised form giving their risk assessment. Among the 206 healthy consultees, 91.3% were women, 92.2% had at least one cancer-affected first-degree relative and 73% had a "cancer family risk" as assessed by the oncogeneticist. Sixty-nine per cent of the consultees were referred to the clinics by a physician, 10.4% by their family and 18.8% on their own initiative: 83.5% of the sample perceived their family risk of cancer as being high and this belief was confirmed in 74.3% of the cases studied by the oncogeneticist. The families of self-referred consultees were less often at risk than those of consultees referred by a physician or by their family (P = 0.012). The majority (78%) expected to be informed about cancer prevention and screening, and this expectation depended on the consultee's level of education (P = 0.001). This study shows that medical pathways are more effective than the media as a means of reaching the members of the general population who are genuinely at risk, and shows that fuller information about prevention needs to be provided at cancer genetic consultations.

We analyzed the hemoglobin patterns of all the adult patients whose hemograms, performed in the hematology laboratory of our hospital, indicated microcytosis (MCV < 82 fl). During a 6 weeks period, 43 cases of microcytosis were identified out of 1827 hemograms and, among them, 16 cases of beta-thalassemia trait were diagnosed, i.e., 0.88%. This rate can probably be extrapolated to the general population of this region. It is in agreement with results obtained by other authors from southeastern France. This frequency of heterozygous beta-thalassemia is non-negligible and strongly suggests that screening for the beta-thalassemia trait in the at risk populations should be undertaken to prevent homozygous forms.