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A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

ABSTRACT: Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per-allele odds ratio = 1·15, 95% confidence interval = 1·05-1·27; P(trend) = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.

SUBMITTER: Hosgood HD

PROVIDER: S-EPMC3253820 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

Hosgood H Dean HD Purdue Mark P MP Wang Sophia S SS Zheng Tongzhang T Morton Lindsay M LM Lan Qing Q Menashe Idan I Zhang Yawei Y Cerhan James R JR Grulich Andrew A Cozen Wendy W Yeager Meredith M Holford Theodore R TR Vajdic Claire M CM Davis Scott S Leaderer Brian B Kricker Anne A Schenk Maryjean M Zahm Shelia H SH Chatterjee Nilanjan N Chanock Stephen J SJ Rothman Nathaniel N Hartge Patricia P Armstrong Bruce B

British journal of haematology 20110120 6

Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0· ...[more]

PMID: 21250972

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Project description:To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls. Among 327 cases and 678 controls, mean doses to the stomach were 15.3 Gy, 24.7 Gy and 1.9 Gy, respectively, for Hodgkin lymphoma, testicular cancer and cervical cancer survivors, with an overall mean dose of 10.3 Gy. Risk increased with increasing radiation dose to the stomach cancer site (P < 0.001) with no evidence of nonlinearity or of a downturn at the highest doses (≥35 Gy). The pooled excess odds ratio per Gy (EOR/Gy) was 0.091 [95% confidence interval (CI): 0.036-0.20] with estimates of 0.049 (95% CI: 0.007-0.16) for Hodgkin lymphoma, 0.27 (95% CI: 0.054-1.44) for testicular cancer and 0.096 (95% CI: -0.002-0.39) for cervical cancer (P homogeneity = 0.25). The EOR/Gy increased with time since exposure (P trend = 0.004), with an EOR/Gy of 0.38 (95% CI: 0.12-1.04) for stomach cancer occurring ≥20 years postirradiation corresponding to odds ratios of 4.8 and 10.5 at radiation doses to the stomach of 10 and 25 Gy, respectively. Of 111 stomach cancers occurring ≥20 years after radiotherapy, 63.8 (57%) could be attributed to radiotherapy. Our findings differ from those based on Japanese atomic-bomb survivors, where the overall EOR/Gy was higher and where there was no evidence of an increase with time since exposure. By pooling data from three studies, we demonstrated a clear increase in stomach cancer risk over a wide range of doses from fractionated radiotherapy with the highest risks occurring many years after exposure. These findings highlight the need to directly evaluate the health effects of high-dose fractionated radiotherapy rather than relying on the data of persons exposed at low and moderate acute doses.

Dataset Information

A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

Publications

A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

Similar Datasets

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