Polymorphism of the CD36 Gene and Cardiovascular Risk Factors in Patients with Coronary Artery Disease Manifested at a Young Age

This study investigates potential associations between CD36 gene variants and the presence of risk factors in Caucasians with coronary artery disease (CAD) manifested at a young age. The study group consisted of 90 patients; the men were ≤ 50 years old and the women were ≤ 55 years old. Amplicons of exons 4 and 5 including fragments of introns were analyzed by DHPLC. Two polymorphisms were found: IVS3-6 T/C (rs3173798) and IVS4-10 G/A (rs3211892). The C allele of the IVS3-6 T/C polymorphism was associated with higher prevalence of obesity and diabetes, higher hsCRP, lower Lp(a) serum concentrations, and younger age at myocardial infarction. The A allele of the IVS4-10 G/A polymorphism was associated with older age of myocardial infarction and higher white blood cell count. The functional role of CD36 polymorphisms in CAD development needs further research

Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

PurposeThis study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs) and to poly(ADP-ribose) polymerase (PARP) inhibitors.MethodsGenetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.ResultsThirty five (22.2%) of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7%) of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%), and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%). In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined) were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined) were identified in the hereditary non-triple-negative group.ConclusionsIdentifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs

Probability of carrying a mutation in genes involved in DNA repair by homologous recombination depending on age at diagnosis of triple-negative breast cancer (A) and hereditary non-triple-negative breast cancer (B).

<p>Fig. 1 was generated using the generalized linear model (glm) function in R environment. See the online supplementary R script (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130393#pone.0130393.s002" target="_blank">S1 Text</a>).</p

List of tested variants.

<p>¹Mutation type according to the HGVS nomenclature</p><p>List of tested variants.</p

Prevalence of germline mutations in genes tested in patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer.

<p>Four patients carried two different mutations:</p><p>¹<i>BRCA1</i>-c.3700_3704delGTAAA/<i>CHEK2</i>-c.470T>C;</p><p>^<i>2</i><i>BRCA1</i>-c.3700_3704delGTAAA/<i>NBN</i>-c.511A>G;</p><p>³<i>CHEK2</i>-c.444+1G>A/<i>NBN</i>-c.511A>G and <i>CHEK2</i>-c.470T>C/<i>NBN</i>-c.657_661delACAAA.</p><p>Prevalence of germline mutations in genes tested in patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer.</p

Prevalence of germline mutations in genes tested in patients with early onset (≤50) triple-negative and hereditary non-triple-negative breast cancer.

<p>Prevalence of germline mutations in genes tested in patients with early onset (≤50) triple-negative and hereditary non-triple-negative breast cancer.</p