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Chad P Garner

Publications and source records attributed to Chad P Garner.

4 recordsLinked to original sources
PubMed2005

Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: strong association of IRS1 G972R variant and cancer risk.

BACKGROUND: As cellular proliferation is central to the carcinogenic process, pathways that regulate proliferation may be important. Therefore, genes in the insulin and the insulin-like growth factor signaling pathways are plausible candidates for susceptibility genes for prostate cancer. We hypothesized that functional polymorphisms in INS, IRS1, IRS2, and IGF1 may be associated with prostate cancer. METHODS: We studied 199 incident prostate cancer cases and 267 age-matched controls. Genotyping was performed for the INS +1127 Ins-PstI, IRS1 G972R, IRS2 G1079D, and the IGF1 CA-repeat polymorphisms. Outcomes were prostate cancer, Gleason score, and AJCC stage. RESULTS: The IRS1 G972R GR/RR genotypes were associated with a significant 2.8-fold increased risk for prostate cancer (95% CI 1.5-5.1, P = 0.0007). The other variants were not significantly associated with prostate cancer. The IRS1 G972R GR/RR genotypes were also significantly associated with more advanced Gleason score (P = 0.001) and AJCC stage (P = 0.004). CONCLUSIONS: These results support a role of the insulin and/or insulin-like growth factor pathways in the etiology of prostate cancer.

Adult↗
PubMed2003

Mixture distribution analysis of phenotypic markers reflecting HFE gene mutations.

The goal of this study was to determine whether statistical modeling of population data for a phenotypic marker could reflect a major locus gene defect. Identifying mutations in the HFE gene makes it possible to assess the association between transferrin saturation (TS) subpopulations and HFE mutations. Data were analyzed from 27 895 white patients who attended a health appraisal clinic and who had TS and common mutations of HFE determined. Mixture distribution modeling of TS was performed, and the proportion of HFE mutations in TS subpopulations was assessed on a probability basis. Three subpopulations of TS were identified, consistent with Hardy-Weinberg conditions for major locus effects. For men, 72% of the subpopulation with the highest mean TS had HFE gene mutations; they were primarily homozygotes or compound heterozygotes. Seventy-three percent of the subpopulation with moderate mean TS also had HFE gene mutations; they were predominantly simple heterozygotes. Sixty-seven percent of the subpopulation with the lowest mean TS were wild-type homozygotes. Similar results were observed for women. These results suggest that statistical modeling of population clinical laboratory test data can reveal the influence of a major locus gene defect and perhaps can be applied to other aspects of body metabolism than iron.

Adult↗
PubMed2002

Evidence of genetic interaction between the beta-globin complex and chromosome 8q in the expression of fetal hemoglobin.

During human development, the switch from fetal to adult hemoglobin (Hb) is not complete with the residual gamma-globin expression being restricted to a subset of erythrocytes termed "F cells" (FC). Statistical analyses have shown the FC trait to be influenced by a common sequence variant (C-->T) at position -158 upstream of the Ggamma-globin gene, termed the "XmnI-Ggamma polymorphism." The XmnI-Ggamma site is believed to be involved in the expression of the Ggamma-globin gene through interaction with transcription factors, and polymorphisms in the transcription factors could be influencing fetal Hb expression, conditional on the XmnI-Ggamma site. Using a two-locus model, in which the second locus was the known quantitative-trait locus (QTL) at the XmnI-Ggamma site, we showed suggestive linkage to chromosome 8q. A maximum single-point LOD score of 4.33 and a multipoint LOD score of 4.75 were found in a 15-20 cM region of chromosome 8q. A single-locus analysis failed to show linkage of FC to the region when the XmnI-Ggamma site was accounted for by removing its effects from the data or including it as a covariate. Results of the single-locus analysis were significant when the effects of the XmnI-Ggamma site were not accounted for in any way. The results of analysis in a large Indian kindred indicate that there is an interaction between the XmnI-Ggamma site and a QTL on chromosome 8q that is influencing the production of fetal Hb.

Chromosome Mapping↗