No Evidence for the Pathogenicity of the BRCA2 c.6937 + 594T>G Deep Intronic Variant: A Case-Control Analysis.

BACKGROUND: The role of deep intronic variants in hereditary cancer susceptibility has been largely understudied. Previously, the BRCA2 c.6937 + 594T>G variant has been shown to preferentially promote the inclusion of a 95 nucleotide cryptic exon and to introduce a premature termination codon. Our objective was to further assess the pathogenicity of the BRCA2 c.6937 + 594T>G deep intronic variant. PATIENTS AND METHODS: We examined the association between BRCA2 c.6937 + 594T>G and breast cancer (BC) risk in 464 BC cases and 497 noncancer controls from Puerto Rico. RESULTS: The overall frequency of the G allele was 2.1% in this population. There was no association between the TG/GG genotypes and BC risk in the uncorrected model and after correcting for confounders. There was only one carrier of the GG genotype. This individual did not have personal or family history of cancer and did not meet the National Comprehensive Cancer Network criteria for hereditary cancer genetic testing. CONCLUSIONS: Although previous work has demonstrated that the BRCA2 c.6937 + 594T>G variant affects splicing, this association study does not support a pathogenic role for the BRCA2 c.6937 + 594T>G intronic variant in breast and ovarian cancer syndrome susceptibility. Furthermore, it emphasizes the need to take into account multiple diverse populations in association studies for the assessment of variant pathogenicity.

Impact of Depression and Inflammation on the Progression of HIV Disease.

The human immunodeficiency virus type 1 (HIV-1) epidemic has negatively affected over 40 million people worldwide. Antiretroviral therapy (ART) has improved life expectancy and changed the outcome of HIV-1 infection, making it a chronic and manageable disease. However, AIDS and non-AIDS comorbid illnesses persist during the course of infection despite the use of ART. In addition, the development of neuropsychiatric comorbidities (including depression) by HIV-infected subjects significantly affects quality of life, medication adherence, and disease prognosis. The factors associated with depression during HIV-1 infection include altered immune response, the release of pro-inflammatory cytokines, and monoamine imbalance. Elevated plasma pro-inflammatory cytokine levels contribute to the development of depression and depressive-like behaviors in HIV+ subjects. In addition, comorbid depression influences the decline rates of CD4+ cell counts and increases plasma viral load. Depression can manifest in some subjects despite their adherence to ART. In addition, psychosocial factors related to stigma (negative attitudes, moral issues, and abuse of HIV+ subjects) are also associated with depression. Both neurobiological and psychosocial factors are important considerations for the effective clinical management of HIV and the prevention of HIV disease progression.