Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma

Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13–1.43, p = 6.77×10−5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34–0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL

HOLA COVID-19 Study: Evaluating the Impact of Caring for Patients With COVID-19 on Cancer Care Delivery in Latin America

PURPOSE The HOLA COVID-19 study sought to evaluate the impact of COVID-19 on oncology practices across Latin America (LATAM), challenges faced by physicians, and how practices and physicians adapted while delivering care to patients with cancer. METHODS This international cross-sectional study of oncology physicians in LATAM included a 43-item anonymous online survey to evaluate changes and adaptations to clinical practice. Multivariable logistic regression analyses were used to evaluate the association of caring for patients with COVID-19 and changes to clinical practice. RESULTS A total of 704 oncology physicians from 19 countries completed the survey. Among respondents, the most common specialty was general oncology (34%) and 56% of physicians had cared for patients with COVID-19. The majority of physicians (70%) noted a decrease in the number of new patients evaluated during the COVID-19 pandemic when compared with prepandemic, and 73% reported adopting the use of telemedicine in their practice. More than half (58%) of physicians reported making changes to the treatments that they offered to patients with cancer. In adjusted models, physicians who had cared for patients with COVID-19 had higher odds of changing the type of chemotherapy or treatments that they offered (adjusted odds ratio 1.81; 95% CI, 1.30 to 2.53) and of delaying chemotherapy start (adjusted odds ratio 2.05; 95% CI, 1.49 to 2.81). Physicians identified significant delays in access to radiation and surgical services, diagnostic tests, and supportive care. CONCLUSION The COVID-19 pandemic has significantly disrupted global cancer care. Although changes to health care delivery are a necessary response to this global crisis, our study highlights the significant disruption and changes to the treatment plans of patients with cancer in LATAM resulting from the COVID-19 health care crisis

Putatively functional SNPs imputed from the ATM locus associated with the risk of NHL.

<p>OR = odds ratio; CI = confidence interval; TFBS = transcription factor binding site; UTR = untranslated region.</p><p>*Correlated tSNP for rs228595 is rs611646; all other SNPs are correlated with the tSNP rs419716.</p

The results of association analysis, displayed as Manhattan plot, after imputation of 28 SNPs genotyped in both stage 1 and 2, which tag 11 DNA repair genes that showed association with NHL risk in our study.

<p>The SNPs and genes are ordered by chromosomal position (x-axis). The associations are displayed as –log₁₀(p-value) for each SNP. Red dots represent fifteen tagging SNPs that were genotyped in our study and were associated with NHL risk. Green dots represent tagging SNPs that were genotyped in our study and that showed no association with NHL. Blue markers represent SNPs imputed by IMPUTE from 1KG. The red dotted line defines the threshold of p-value <0.05. * indicates an associated SNP with a putatively functional impact; non-synonymous coding change or SNP mapping in: transcription factor binding site, H3K4Me1 chromatin mark, DNaseI hypersensitivity cluster, 5′UTR, 3′UTR.</p

Association analysis of rs1805812 x rs625245 interactions between <i>MRE11A</i> and <i>NBS1</i> with the risk of NHL.

<p>OR = odds ratio; CI = confidence interval.</p