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Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma.

ABSTRACT: OBJECTIVE:Sun exposure and sensitivity, including pigmentation, are associated with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the independent roles of these IRF4 polymorphisms and sun sensitivity in mediating NHL risk and explored whether they are confounded or modified by each other. METHODS:Genotyping of tag single nucleotide polymorphisms (SNPs) in the IRF4 gene was conducted in 990 NHL cases and 828 controls from a multi-center US study. Measures of sun sensitivity and exposure were ascertained from computer-assisted personal interviews. We used logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI) for NHL in relation to sun exposures, sun exposures in relation to IRF4 genotypes, and NHL in relation to sun exposures. We further assessed the effects of sun exposures in relation to IRF4 genotypes. RESULTS:As previously reported, we found significant associations between IRF4 rs12211228 and NHL and between hair and eye color and NHL. The IRF4 rs12203592 polymorphism (CT/TT genotype) was statistically significantly associated with eye color and particularly with hair color (OR(Light Blonde) = 0.24, 95% CI = 0.11-0.50, overall Chi square p = 0.0002). Analysis of joint effects between eye and hair color with the IRF4 rs12203592 SNP did not reveal statistically significant p-interactions although NHL risk did decline with lighter hair color and presence of the variant IRF4 rs12203592 allele, compared to those without a variant allele and with black/brown hair color. CONCLUSIONS:Our data do not statistically support a joint effect between IRF4 and sun sensitivity in mediating risk for NHL. Further evaluation of joint effects in other and larger populations is warranted.

SUBMITTER: Gathany AH

PROVIDER: S-EPMC2746901 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma.

Gathany Allison H AH Hartge Patricia P Davis Scott S Cerhan James R JR Severson Richard K RK Cozen Wendy W Rothman Nathaniel N Chanock Stephen J SJ Wang Sophia S SS

Cancer causes & control : CCC 20090428 8

<h4>Objective</h4>Sun exposure and sensitivity, including pigmentation, are associated with risk for non-Hodgkin lymphoma (NHL). One variant in the immune regulatory factor 4 (IRF4) gene (rs12203592) is associated with pigmentation, and a different IRF4 variant (rs12211228) is associated with NHL risk. We evaluated the independent roles of these IRF4 polymorphisms and sun sensitivity in mediating NHL risk and explored whether they are confounded or modified by each other.<h4>Methods</h4>Genotypi ...[more]

PMID: 19396635

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Project description:ImportanceUnderstanding patterns of sun-protective behaviors and their association with sunburn can provide important insight into measurement approaches and intervention targets.ObjectiveTo assess whether decision-based modeling can be used to identify patterns of sun-protective behaviors associated with the likelihood of sunburn and to compare the predictive value of this method with traditional (ie, composite score) measurement approaches.Design, setting, and participantsThis cross-sectional study used a nationally representative sample of 31?162 US adults from the 2015 National Health Interview Survey, consisting of household interviews conducted in person and completed by telephone when necessary. Participants included civilian noninstitutionalized US adults. Data were collected from January 1 through December 31, 2015.Main outcomes and measuresThe associations among sun sensitivity, multiple sun-protective behaviors (ie, using sunscreen, seeking shade, wearing a hat, and wearing protective clothing), and sunburn were examined using a ?2 automatic interaction detection method for decision tree analysis. Results were compared with a composite score approach.ResultsIn our study population of 28?558 respondents with complete data (54.1% women; mean [SD] age, 49.0 [18.0] years), 20 patterns of sun protection were identified. Among 15?992 sun-sensitive individuals, those who used only sunscreen had the highest likelihood of sunburn (62.4%). The group with the lowest likelihood of sunburn did not report using sunscreen but engaged in the other 3 protective behaviors (24.3% likelihood of sunburn). Among 12?566 non-sun-sensitive individuals, those who engaged in all 4 protective behaviors had the lowest likelihood of sunburn (6.6%). The highest likelihood of sunburn was among those who only reported sunscreen use (26.2%). The decision tree model and the composite score approach correctly classified a similar number of cases; however, the decision tree model was superior in classifying cases with sunburn (44.3% correctly classified in the decision tree vs 25.9% with the composite score).Conclusions and relevanceThis innovative application of a decision tree analytic approach demonstrates the interactive and sometimes counterintuitive effects of multiple sun-protective behaviors on likelihood of sunburn. These data show where traditional measurement approaches of behavior may fall short and highlight the importance of linking behavior to a clinically relevant outcome. Given the scope of those affected and enormous associated health care costs, improving efforts in skin cancer prevention has the potential for a significant effect on public health.

Dataset Information

Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma.

Publications

Relationship between interferon regulatory factor 4 genetic polymorphisms, measures of sun sensitivity and risk for non-Hodgkin lymphoma.

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