No loss of heterozygosity (LOH) in tumor tissue and no allelic imbalance in RNA level were confirmed. The clinical relevance of the BRCA2 C-terminal stop codon variants is controversial. The pathogenic role of the germline BRCA2 c.9976A>T and c.10095delinsGAATTATATCT variants in hereditary breast and ovarian cancer (HBOC) patients was evaluated. An association with clinicopathological parameters was performed in 2491 independent probands diagnosed with HBOC and in 122,209 cancer patients reported earlier. Loss-of-heterozygosity (LOH) in tumor samples and allelic imbalance in RNA extracted from peripheral blood cells were investigated. Neither c.10095delinsGAATTATATCT or c.9976A>T variants showed significant association with clinicopathological parameters or elevated risk for HBOC-associated tumors.

Lung cancer was more prevalent in families carrying the c.9976A>T variant compared to pathogenic BRCA1 or BRCA2 carrier families. An increased prevalence of pancreatic cancer was found in families where c.9976A>T occurred together with other pathogenic BRCA1 variants. An increased risk for familial pancreatic, lung and upper aero-digestive tract cancers was confirmed in the validation set. Regarding BRCA2 C-terminal variants, no linkage with other pathogenic BRCA2 variants, no LOH in tumor tissue and no allelic imbalance in RNA level were confirmed. The c.9976A>T variant may be considered as a potential risk for lung cancer, and a potential modifying factor in pancreatic cancer when it occurs along with the pathogenic BRCA1 variant, although this observation should be validated in a larger sample cohort. In the American College of Medical Genetics and Genomics (ACMG) classification system stop codon (truncation) variants are usually considered to be pathogenic/likely pathogenic. 2Division of Food Control, National Food Agency, Uppsala, Sweden.1Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.Additionally, stop codon variants of the BRCA2 gene are frequent among all pathogenic variants, leading to a significant increase in the risk of breast and ovarian cancer. The United Nations sustainable development goals include eradication of hunger.

To feed 10 billion persons 2050, we need to get the trade-offs right between sustainability, food security, food safety, and make better use of food already produced. The hierarchy of strategies for reducing food losses and waste are in descending order source reduction, reusing or reprocessing surplus foods, recycle food as feed for animals, recover the energy as biofuels, nutrients as compost, or raw materials for industry, while as last resorts one may consider recovering the energy by incineration or dumping as garbage in landfills. This paper will explore the trade-offs inherent when aiming at triple goals of sustainability, food security, and safety looking at these strategies for reducing food losses and waste and resource footprints. Intensification of food production and circular food systems could be parts of these solutions to future food security. In this regard could our future trade-offs be informed by the experiences from the use of antimicrobials to intensify food production and from the outbreak of bovine spongiform encephalopathy (BSE) in terms of circular food production? There is no trade-off between intensification of food production aided by antimicrobials and the public health risks from antimicrobial resistance due to the zoo-technical use of antimicrobials. A sustainable future requires control of antimicrobial resistance. If one avoids that cycles of nutrients become cycles of pathogens and/or hazards, circular food production systems will a major contribution to the future sustainable food security.

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