(searched for: doi:10.1186/s12881-020-01156-1)
Overcoming Drug Resistance in Gynecologic Cancers pp 169-193; https://doi.org/10.1016/b978-0-12-824299-5.00009-5
The role of genetic predisposition in cancer pathogenesis is well known. Despite the fact that in many cases exact mechanisms cannot be understood, overall observational and experimental data confirm the role of hereditary factors in cancer development and progression. Gynecologic cancers are not an exception. Increased risk for these tumors in the families of affected individuals lead to intensive research aggravated by huge data from GWAS. It seems like an insight into genetic pathways not only helps in understanding the disease development, but also designs more precise treatment options with better results and less side effects. Currently, there are no many clinical decisions in gynecologic cancer management that need to be based on genetic predisposition analysis, although increasing interest and availability of new technologies will probably soon make incorporation of hereditary factors in management possible. As expected, the genetic variants causing markedly elevated risk are rather rare, but those, associated with mild or moderate risk are numerous, quite common and especially important when analyzed in clusters. There are peculiarities of large-scale population studies, which determine a need of time for development and translation of significant scientific knowledge, but at this point, increased interest has resulted in rapid accumulation of reproducible data. The main approach of medicine is treating people, not the diseases. Heredity is a part of each patient and given the current progress in science and medicine, the era when understanding the genetic background will become a part of every physician’s life approaching.
Published: 1 May 2021
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Genes & Immunity, Volume 22, pp 65-74; https://doi.org/10.1038/s41435-021-00130-y
Immunogenetic studies in the past three decades have uncovered a broad range of human genetic factors that seem to influence heterosexual HIV-1 transmission in one way or another. In our own work that jointly evaluated both genetic and nongenetic factors in two African cohorts of cohabiting, HIV-1-discordant couples (donor and recipient pairs) at risk of transmission during quarterly follow-up intervals, relatively consistent findings have been seen with three loci (IL19, HLA-A, and HLA-B), although the effect size (i.e., odds ratio or hazards ratio) of each specific variant was quite modest. These studies offered two critical lessons that should benefit future research on sexually transmitted infections. First, in donor partners, immunogenetic factors (e.g., HLA-B*57 and HLA-A*36:01) that operate directly through HIV-1 viral load or indirectly through genital coinfections are equally important. Second, thousands of single-nucleotide polymorphisms previously recognized as “causal” factors for human autoimmune disorders did not appear to make much difference, which is somewhat puzzling as these variants are predicted or known to influence the expression of many immune response genes. Replicating these observations in additional cohorts is no longer feasible as the field has shifted its focus to early diagnosis, universal treatment, and active management of comorbidities.