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Daniele Campa,
Katja Butterbach,
Susan L Slager,
Christine F Skibola,
Silvia de Sanjosé,
Yolanda Benavente,
Nikolaus Becker,
Lenka Foretova, Marc Maynadie,
Pierluigi Cocco, [......],
Paul Brennan,
Lucia Conde,
Paige M Bracci,
Neil E Caporaso,
Sara S Strom,
Nicola J Camp,
James R Cerhan,
Gec Consortium,
Federico Canzian,
Alexandra Nieters
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ABSTRACT: Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular "xenosensors" like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2 and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the four genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European case-control study (EpiLymph) using the Illumina GoldenGate™ assay technology. Carriers of the SNP rs6857600 minor allele in ABCG2 was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p < 0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p = 0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL.
International Journal of Cancer 09/2011; 131(4):803-12. · 5.44 Impact Factor
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Katja Butterbach,
Lars Beckmann,
Silvia de Sanjosé,
Yolanda Benavente,
Nikolaus Becker,
Lenka Foretova, Marc Maynadie,
Pierluigi Cocco,
Anthony Staines,
Paolo Boffetta,
Paul Brennan,
Alexandra Nieters
[show abstract]
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ABSTRACT: Previous studies have suggested an important role for the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in tumour development. Therefore, we explored genetic variants in JAK-STAT pathway associated genes with lymphoma risk. In samples of the EpiLymph case-control study we genotyped 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArray™ Technology (Illumina, San Diego, CA, USA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (B-NHL) and most frequent B-NHL subtypes. Among 210 relevant JAK-STAT pathway-related SNPs, polymorphisms in nine genes (BMF, IFNG, IL12A, SOCS1, STAT1, STAT3, STAT5A, STAT6, TP63) were significantly associated with lymphoma risk. At a study-wise significance level, we obtained a risk reduction of 28% among carriers of the heterozygous genotype of the STAT3 variant (rs1053023) for B-NHL. For six other variants within the STAT3 gene we observed an inverse association with different lymphoma subtypes. A reduced risk for HL was observed for the heterozygous genotype of the STAT6 SNP (rs324011). This is an explorative investigation to examine associations between JAK-STAT signalling related genes and lymphoma risk. The results implicate a relevant role of certain pathway-related genes in lymphomagenesis, but still need to be approved by independent studies.
British Journal of Haematology 03/2011; 153(3):318-33. · 4.94 Impact Factor
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Christine F Skibola,
Paige M Bracci,
Alexandra Nieters,
Angela Brooks-Wilson,
Silvia de Sanjosé,
Ann Maree Hughes,
James R Cerhan,
Danica R Skibola,
Mark Purdue,
Eleanor Kane, [......],
Alex Smith,
Renee Shiao,
Anne J Novak, Marc Maynadie,
Stephen J Chanock,
Anthony Staines,
Theodore R Holford,
Elizabeth A Holly,
Nathaniel Rothman,
Sophia S Wang
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ABSTRACT: In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.
American journal of epidemiology 02/2010; 171(3):267-76. · 5.59 Impact Factor
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Yawei Zhang,
Silvia De Sanjose,
Paige M Bracci,
Lindsay M Morton,
Rong Wang,
Paul Brennan,
Patricia Hartge,
Paolo Boffetta,
Nikolaus Becker, Marc Maynadie,
Lenka Foretova,
Pierluigi Cocco,
Anthony Staines,
Theodore Holford,
Elizabeth A Holly,
Alexandra Nieters,
Yolanda Benavente,
Leslie Bernstein,
Shelia Hoar Zahm,
Tongzhang Zheng
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ABSTRACT: Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988-2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.
American journal of epidemiology 07/2008; 167(11):1321-31. · 5.59 Impact Factor
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Eleanor V Willett,
Lindsay M Morton,
Patricia Hartge,
Nikolaus Becker,
Leslie Bernstein,
Paolo Boffetta,
Paige Bracci,
James Cerhan,
Brian C-H Chiu,
Pierluigi Cocco, [......],
Eva Negri,
Alexandra Nieters,
Richard Severson,
Susan L Slager,
John J Spinelli,
Anthony Staines,
Renato Talamini,
Martine Vornanen,
Dennis D Weisenburger,
Eve Roman
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ABSTRACT: Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL, self-reported anthropometric data on weight and height from over 10,000 cases of NHL and 16,000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m(-2) or more, was not associated with NHL overall (pooled OR = 1.00, 95% confidence interval (CI) 0.70-1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR = 1.80, 95% CI 1.24-2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25-29.9 kg m(-2)) and obese (BMI 30-39.9 kg m(-2)), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI < 18.5 kg m(-2)). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m(-2) rise in BMI above 18.5 kg m(-2). BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR = 1.19, 95% CI 1.06-1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation.
International Journal of Cancer 05/2008; 122(9):2062-70. · 5.44 Impact Factor
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Sophia S Wang,
Susan L Slager,
Paul Brennan,
Elizabeth A Holly,
Silvia De Sanjose,
Leslie Bernstein,
Paolo Boffetta,
James R Cerhan, Marc Maynadie,
John J Spinelli, [......],
Dennis Weisenburger,
Scott Davis,
Silvia Franceschi,
Carlo La Vecchia,
Lenka Foretova,
Nikolaus Becker,
Anthony Staines,
Martine Vornanen,
Tongzhang Zheng,
Patricia Hartge
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ABSTRACT: A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.
Blood 05/2007; 109(8):3479-88. · 9.90 Impact Factor
