RESUMO
Genetic causes of the global decline in male fertility are among the hot spots of scientific research in reproductive genetics. The most common way to evaluate male fertility in clinical trials is to determine semen quality. Lower semen quality is very often accompanied by subfertility or infertility, occurs in many diseases and can be caused by many factors, including genetic ones. The following forms of lowered semen quality (pathozoospermia) are known: azoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and some combined forms. To systematize information about the genetic basis of impaired spermatogenesis, we created a catalog of human genes associated with lowered semen quality (HGAPat) and analyzed their functional characteristics. The catalog comprises data on 126 human genes. Each entry of the catalog describes an association between an allelic variant of the gene and a particular form of lowered semen quality, extracted from the experimental study. Most genes included into the catalog are located on autosomes and are associated with such pathologies as non-obstructive azoospermia, oligozoospermia or asthenozoospermia. Slightly less than half of the included genes (43%) are expressed in the testes in a tissue-specific manner. Functional annotation of genes from the catalog showed that spermatogenic failure can be associated with mutations in genes that control biological processes essential for spermiogenesis (regulating DNA metabolism, cell division, formation of cellular structures, which provide cell movement) as well as with mutations in genes that control cellular responses to unfavorable conditions (stress factors, including oxidative stress and exposure to toxins).
RESUMO
INTRODUCTION: There is some evidence suggesting a link between BRCA1/2 germline mutations and increased risk of gastric cancer. METHODS: Endoscopic screening for stomach malignancies was performed in 120 BRCA1 mutation carriers in order to evaluate the probability of detecting the tumor disease. RESULTS: No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I-IV alterations were observed in 26 of 41 (63%) subjects aged >50 years as compared to 29 of 79 (37%) in younger subjects (p = 0.007, χ2 test). One BRCA1 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from BRCA1/2 mutation carriers. Somatic loss of the remaining BRCA1/2 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained BRCA1/2 copy, showed chromosomal instability. CONCLUSION: Taken together, these data justify further studies on the relationships between the BRCA1/2 and gastric cancer.
