Hodgkin Disease Therapy Induced Second Malignancy Susceptibility 6q21 Functional Variants in Roma and Hungarian Population Samples

Abstract

Patients treated successfully for pediatric Hodgkin's lymphoma are known to develop secondary malignancies; care is already taken in treatment to prevent this adverse effect. Recent GWAS study identified rs4946728 and rs1040411 noncoding SNPs located between PRDM1 and ATG1 genes on chromosome 6q21 as risk factors for secondary malignancies in patients formerly treated with radiotherapy for pediatric Hodgkin disease. We investigated the allele frequencies of these two SNPs in biobanked, randomly selected DNA of average, apparently healthy Hungarians (n = 277) and in samples of Roma (n = 279) population living Hungary. The risk allele frequency for rs4946728 was 79.4 % in Hungarian and 83.5 % in Roma samples, while for rs1040411 it was 56.4 % in Hungarian and 55.8 % in Roma samples. These values are quite similar in the two populations, and are rather high. The values are higher than those frequencies observed in the controls (rs4946728: 59.1 % and rs1040411: 39.6 %, p < 0.05), and are in the range of the cases (86 % and 68.2 %, respectively) of the above original GWAS study. Our findings suggest, that beside the already taken precautions, genetic characterization of Hungarian pediatric Hodgkin patients seems to be advantageous prior to the treatment of their disease.

Pediatric Hodgkin lymphoma- biomarkers, drugs, and clinical trials for translational science and medicine

“…Two independent genome wide association studies (GWAS) reported that variants at chromosome 6q21 in pediatric HL patients were associated with radiation induced second malignant neoplasms (SMNs) [89, 90]. Best and colleagues revealed significant associations between SNPs on chromosome 6q21, rs4946728 ( P = 0.002), and rs1040411 ( P = 0.03) and the odds of developing SMNs, which increased by >3-fold and >2-fold per copy of the major allele rs4946728 and rs1040411, respectively [89].…”

Current survivorship recommendations for patients with Hodgkin lymphoma: focus on late effects

“…[6][7][8] Best et al showed 2 variants at chromosome 6q21 to be associated with subsequent malignant neoplasm in survivors of HL treated with radiation therapy as children but not as adults. 6 Ma et al showed that genetic variation in FGFR2 influences breast cancer risk in HL patients treated with radiotherapy.…”

Radiation induced secondary malignancies: a review article

“…Recently, genome-wide association studies (GWAS) have identified rs4946728 and rs1040411 non-coding single nucleotide polymorphisms (SNPs) located on chromosome 6q21 as a risk factor for RISM in pediatric HL. Varszegi et al [ 9 ] investigated the frequencies of the two SNPs (those identified in GWAS study) in healthy Hungarians and Romanians. The percentage of these SNPs was higher than those observed in controls and are in the range of the cases of the original GWAS study.…”