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A majority of B- and T-cell leukemias and lymphomas which are associated with chromosomal abnormalities that bear the hallmarks of aberrant V(D)J or class-switch recombination are described and the cost is genomic instability and its potential contribution to malignancy. Examples of B-cell lymphomas are also explained with point mutations in proto-oncogenes consistent with a role for somatic hypermutation (SHM).

Epidemiological studies suggest that populations consuming typical Asian diets have a lower incidence of hormone-dependent cancers than populations consuming Western diets. These dietary differences have been mainly attributed to higher soy intakes among Asians. However, studies from our laboratory suggest that the anti-estrogenic effects of dietary kelp also may contribute to these reduced cancer rates. As a follow-up to previous findings of endocrine modulation related to kelp ingestion in a pilot study of premenopausal women, we investigated the endocrine modulating effects of kelp (Fucus vesiculosus) in female rats and human luteinized granulosa cells (hLGC). Kelp administration lengthened the rat estrous cycle from 4.3 [+ or -] 0.96 to 5.4 [+ or -] 1.7 d at 175 mg * [kg.sup.-1] body wt * [d.sup.-1] (P = 0.05) and to 5.9 [+ or -] 1.9 d at 350 mg * [kg.sup.-1] * [d.sup.-1] (P = 0.002) and also led to a 100% increase in the length of diestrus (P = 0.02). Following 175 mg * [kg.sup.-1] * [d.sup.-1] treatment for 2 wk, serum 17 [beta]-estradiol levels were reduced from 48.9 [+ or -] 4.5 to 40.2 [+ or -] 3.2 ng/L (P = 0.13). After 4 wk, 17 [beta]-estradiol levels were reduced to 36.7 [+ or -] 2.2 ng/L (P = 0.02). In hLGC, 25, 50, and 75 [micro]mol/L treatment reduced 17 [beta]-estradiol levels from 4732 [+ or -] 591 to 3632 [+ or -] 758, 3313 [+ or -] 373, and 3060 [+ or -] 538 ng/L, respectively. Kelp treatment also led to modest elevations in hLGC culture progesterone levels. Kelp extract inhibited the binding of estradiol to estrogen receptor [alpha] and [beta] and that of progesterone to the progesterone receptor, with I[C.sub.50] values of 42.4, 31.8, and 40.7 [micro]mol/L, respectively. These data show endocrine modulating effects of kelp at relevant doses and suggest that dietary kelp may contribute to the lower incidence of hormone-dependent cancers among the Japanese. KEY WORDS: * Fucus vesiculosus * rat * seaweed * breast cancer * estrogen

In a recent genome-wide association study of follicular lymphoma (FL), we identified novel risk alleles on chromosome 6p21.33 that appeared to be part of an extended haplotype including HLA-DRB1*0101, DQA1*0101, and DQB1*0501. To follow up on these findings, we obtained 2-4 digit HLA-DQB1 allelotypes on a subset of 265 cases of FL and 757 controls using a novel assay that applies multiplexed ligation-dependent probe amplification (MLPA). We confirmed a positive association between FL and the HLA- DQB1*05 allele group (OR = 1.70, 95% CI 1.28-2.27; adjusted p-value = 0.013) and also identified an allele group inversely associated with FL risk, HLA-DQB1*06 (OR = 0.51, 95% CI 0.38-0.69; adjusted p-value = 4.46 × 10−5). Although these findings require verification, the role of HLA class II proteins in B-cell survival and proliferation makes this a biologically plausible association. [ABSTRACT FROM AUTHOR]

As benzene has been linked with elevated risk of both acute myeloid leukemia and lymphoma, we explored the effect of benzene exposure on levels of t(8;21), t(15;17), and t(14;18) translocations. Circulating lymphocytes of normal individuals also often contain t(14;18). Quantitative polymerase chain reaction analysis showed that 37 workers with benzene exposure had a decreased level of t(14;18) in their blood with only 16.2% having 10 or more copies of the t(14;18) BCL-2/IgH fusion gene/microg DNA, as opposed to 55% of 20 controls (P = .0063 by Fisher's exact test). This decline may be related to the immunotoxicity to specific subtypes of circulating B-lymphocytes, but the data do not support the use of t(14;18) as a biomarker of increased lymphoma risk in benzene-exposed populations. None of 88 individuals (31 controls and 57 exposed) exhibited detectable t(8;21) transcripts, and while t(15;17) transcripts were detected in two individuals, the result is inconclusive as one was exposed and the other was unexposed.

Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations.