Association between xenobiotic gene polymorphisms and non‐Hodgkin's lymphoma risk

Abstract

Summary. The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively.Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR ¼ 4AE27; 95% CI, 2AE40-7AE61, P < 0AE001) and PON1 BB a 2AE9-fold increase (OR ¼ 2AE92; 95% CI, 1AE49-5AE72, P ¼ 0AE002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.

Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma

“…Three previous smaller epidemiologic investigations found no association between NAT1 or NAT2 genotypes and NHL risk [16,18,19]; a fourth epidemiologic investigation, which used caffeine as a metabolic probe to determine acetylation status, also found no significant relationship between acetylation status and overall malignant lymphoma but did suggest an association between the NAT2 slow-acetylator phenotype and low-grade lymphoma [17]. The NAT1 and NAT2 genotype frequencies in our controls were similar to the control populations in previous studies.…”

“…NAT1 and NAT2 appear to demonstrate some substrate specificity and varying levels of expression in different tissues [12,13]. Well-established sequence variation that corresponds to variation in acetylation capacity, and thus carcinogen metabolism, has been identified for NAT2 [13,15], but investigation of genetic variation in NAT1 and NAT2 in relation to NHL risk has been limited and inconsistent to date [16][17][18][19].…”

Clinical and biological relevance of single-nucleotide polymorphisms and acquired somatic mutations of the BCL6 first intron in follicular lymphoma

“…In NHL, SNPs of several genes have been previously related to lymphoma susceptibility, such as genes coding for xenobiotic proteins (GSTT1, PON1, Methionine synthase), 26,27 inflammation regulator cytokines (IL1, IL10, TNFa), [28][29][30] mismatch repairing elements (hMSH2), 31 or oncoproteins (H-ras 1). 32 Since BCL6 plays a crucial role during both normal B-cell maturation and lymphomagenesis, it has been hypothesized that constitutional or acquired mutations of putative functional elements may impact on lymphoma predisposition or lymphoma outcome.…”

Polymorphisms in xenobiotic‐metabolizing genes and the risk of chronic lymphocytic leukemia and non‐Hodgkin's lymphoma in adult Russian patients

“…Thus, it would be interesting to investigate associations between polymorphous variants of xenobiotic-metabolizing genes and risk of development of other lymphoproliferative diseases. The data concerning B-CLL and NHL susceptibility regarding xenobiotic-metabolizing genes status are limited and sometimes contradictory [26][27][28][29][30][31][32]. There might be gender-specific and subtype-specific associations that require further investigations.…”