No abstract

Some autoimmune disorders are increasingly recognized as risk factors for nonHodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of selfreported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (

Glutathione S -transferases (GSTs) detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Functional polymorphisms exist in at least three genes that encode GSTs, including GSTM1, GSTT1, and GSTP1. We hypothesize, therefore, that polymorphisms in genes that encode GSTs alter susceptibility to chemotherapy-induced carcinogenesis, specifically to therapy-related acute myeloid leukemia (t-AML), a devastating complication of long-term cancer survival. Elucidation of genetic determinants may help to identify individuals at increased risk of developing t-AML. To this end, we have examined 89 cases of t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in GSTM1, GSTT1, and GSTP1 . Gene deletion of GSTM1 or GSTT1 was not specifically associated with susceptibility to t-AML. Individuals with at least one GSTP1 codon 105 Val allele were significantly over-represented in t-AML cases compared with de novo AML cases [odds ratio (OR), 1.81; 95% confidence interval (CI), 1.11–2.94]. Moreover, relative to de novo AML, the GSTP1 codon 105 Val allele occurred more often among t-AML patients with prior exposure to chemotherapy (OR, 2.66; 95% CI, 1.39–5.09), particularly among those with prior exposure to known GSTP1 substrates (OR, 4.34; 95% CI, 1.43–13.20), and not among those t-AML patients with prior exposure to radiotherapy alone (OR,1.01; 95% CI, 0.50–2.07). These data suggest that inheritance of at least one Val allele at GSTP1 codon 105 confers a significantly increased risk of developing t-AML after cytotoxic chemotherapy, but not after radiotherapy.

In 2004-2007 4 independent case-control studies reported evidence that sun exposure might protect against NHL; a fifth, in women only, found increased risks of NHL associated with a range of sun exposure measurements. These 5 studies are the first to examine the association between personal sun exposure and NHL. We report here on the relationship between sun exposure and NHL in a pooled analysis of 10 studies participating in the International Lymphoma Epidemiology Consortium (InterLymph), including the 5 published studies. Ten case-control studies covering 8,243 cases and 9,697 controls in the USA, Europe and Australia contributed original data for participants of European origin to the pooled analysis. Four kinds of measures of self-reported personal sun exposure were assessed at interview. A two-stage estimation method was used in which study-specific odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders including smoking and alcohol use, were obtained from unconditional logistic regression models and combined in random-effects models to obtain the pooled estimates. Risk of NHL fell significantly with the composite measure of increasing recreational sun exposure, pooled OR 5 0.76 (95% CI 0.63-0.91) for the highest exposure category (p for trend 0.01). A downtrend in risk with increasing total sun exposure was not statistically significant. The protective effect of recreational sun exposure was statistically significant at 18-40 years of age and in the 10 years before diagnosis, and for B cell, but not T cell, lymphomas. Increased recreational sun exposure may protect against NHL. ' 2007 Wiley-Liss, Inc.Key words: non Hodgkin lymphoma; personal sun exposure; pooled analysis It was suggested at first that sunlight might increase risk for non-Hodgkin lymphoma (NHL) because of parallel upwards trends in incidence of melanoma and NHL, a positive geographical correlation between incidence rates of NHL and non-melanocytic skin cancer and an increased risk of NHL in people with a history of skin cancer. [1][2][3][4] Four independent studies directly relating personal sun exposure to NHL risk have suggested the opposite however: that sunlight might protect against NHL.5-8 Reduced risks of NHL were associated with increasing sun exposure on non-working days or vacations in an Australian population, 5 more sunbathing, sunburns and sunlamp exposure in the large SCALE study in Sweden and Denmark,6 with greater exposure to the midday summer sun, greater residential ambient UV and greater sunlamp or tanning booth exposure in a US study, 7 and with using sunbeds or sunlamps and taking holidays in a sunny climate in a German study. 8 One such study, which included only women in Connecticut, has found increased risks of NHL associated with a range of sun exposure measurements including having a suntan for less than 3 months a year and a suntan history of more than 60 years, and with increasing duration of spending time in strong sunlight in summer; the increased risk was particularly for chro...