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The Relationship Between Environmental Exposure and Genetic Architecture of the 2q33 Locus With Esophageal Cancer in South Africa.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) has a high prevalence in several countries in Africa and Asia. Previous genome-wide association studies (GWAS) in Chinese populations have identified several ESCC susceptibility loci, including variants on chromosome 2q33 and 6p21, but the contribution of these loci to risk in African populations is unknown. In this study we tested the association of 10 genetic variants at these two risk loci on susceptibility to ESCC in two South African ethnic groups. Variants at 2q33 (rs3769823, rs10931936, rs13016963, rs7578456, rs2244438) and 6p21 (rs911178, rs3763338, rs2844695, rs17533090, rs1536501) were genotyped in a set of Black Xhosa (463 cases and 480 controls) and Mixed Ancestry (269 cases and 288 controls) individuals. Genotyping was performed using TaqMan allelic discrimination assays. The Pearson's chi-squared test was used to compare the allele frequency between cases and controls. Gene-environment interactions with tobacco smoking and alcohol consumption were investigated in a case-control analysis. A logistic regression analysis was further performed to elucidate the independent effect of each association signal on the risk of ESCC. The 2q33 variants rs10931936, rs7578456, and rs2244438 were marginally associated with higher risk of ESCC in the Mixed Ancestry population (ORs = 1.39-1.58, p ? 0.035), of which rs7578456 and rs2244438 remained significant after multiple correction (p < 0.005). The associations with rs7578456 and rs2244438 were also observed across strata of tobacco smoking (ORs = 1.47-2.75, p ? 0.035) and alcohol consumption (ORs = 1.45-2.06, p ? 0.085) status. However, only the association with rs2244438, which lies within an exon of TRAK2, remained significant after adjustment for the other variants in the region. Interestingly, none of the variants tested were significantly associated with ESCC in the Black South African population. These finding implicate TRAK2 as a casual gene for ESCC risk in the Mixed Ancestry population of South Africa and confirm prior evidence of population-specific differences in the genetic contribution to ESCC, which may reflect differences in genetic architecture and environmental exposure across ethnic groups.

SUBMITTER: Matejcic M

PROVIDER: S-EPMC6504765 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Relationship Between Environmental Exposure and Genetic Architecture of the 2q33 Locus With Esophageal Cancer in South Africa.

Matejcic Marco M Mathew Christopher G CG Parker M Iqbal MI

Frontiers in genetics 20190501

Esophageal squamous cell carcinoma (ESCC) has a high prevalence in several countries in Africa and Asia. Previous genome-wide association studies (GWAS) in Chinese populations have identified several ESCC susceptibility loci, including variants on chromosome 2q33 and 6p21, but the contribution of these loci to risk in African populations is unknown. In this study we tested the association of 10 genetic variants at these two risk loci on susceptibility to ESCC in two South African ethnic groups. ...[more]

PMID: 31118947

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Project description:Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control--traits also associated with neuroticism--and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious) and feel that they are in control of their own destiny (internal locus of control). We discuss that some of the genes underlying this relationship may include those influencing the function of dopaminergic neural systems.

Dataset Information

The Relationship Between Environmental Exposure and Genetic Architecture of the 2q33 Locus With Esophageal Cancer in South Africa.

Publications

The Relationship Between Environmental Exposure and Genetic Architecture of the 2q33 Locus With Esophageal Cancer in South Africa.

Similar Datasets

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