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High-risk Genotypes (high-risk + genotype)

Distribution by Scientific Domains

Medical Sciences	85%

Selected Abstracts

Genetic association tests with age at onset

GENETIC EPIDEMIOLOGY, Issue 2 2003
L. Hsu
Abstract Many diseases or traits exhibit a varying age at onset. Recent data examples of prostate cancer and childhood diabetes show that compared to simply treating the disease outcome as affected vs. unaffected, incorporation of age-at-onset information into the transmission/disequilibrium type of test (TDT) does not appear to change the results much. In this paper, we evaluate the power of TDT as a function of age at onset, and show that age-at-onset information is most useful when the disease is common, or the relative risk associated with the high-risk genotype varies with age. Moreover, an extremely old unaffected subject can contribute substantially to the power of the TDT, sometimes as much as old-onset subjects. We propose a modified test statistic for testing no association between the marker at the candidate locus and age at onset. The simulation study was conducted to evaluate the finite sample properties of proposed and the TDT test statistics under various sampling schemes for trios of parents and offspring, as well as for sibling clusters where unaffected siblings were used as controls. Genet Epidemiol 24:118,127, 2003. © 2003 Wiley-Liss, Inc. [source]

Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma

CANCER, Issue 5 2008
Paul Wheatley-Price MB
Abstract BACKGROUND. Pancreatic cancer risk has been linked to chronic pancreatitis and periodontitis, suggesting a role for inflammation in disease etiology. Myeloperoxidase (MPO) and superoxide dismutase (SOD2) are enzymes that regulate reactive oxygen species and contain recognized single nucleotide polymorphisms (SNPs) that confer altered enzyme activity. METHODS. One hundred twenty-two patients with pancreatic cancer and 331 age- and sex-matched controls were analyzed for polymorphisms of the MPO , guanine 463 adenine (,G463A) and the SOD2 alanine (Ala)-to-valine (Val) polymorphism at codon 16 (Ala16Val) genes. Cases and controls were analyzed for associations between these polymorphisms, adjusting for sex, age, history of alcohol use and smoking history. RESULTS. The variant A allele of MPO ,G463A was associated with a lower risk of pancreatic cancer (adjusted odds ratio [OR] for pancreatic cancer, 0.57; 95% confidence interval [95% CI], 0.4,0.9; P = .02). The SOD2 homozygous variant genotype (Val/Val) was associated with a greater risk of pancreatic cancer (adjusted OR, 1.96; 95% CI, 1.0,3.8; P = .04). Compared with individuals who carried both low-risk alleles (A/, and Ala/,), significantly more cases than controls carried both high-risk genotypes (G/G and Val/Val; adjusted OR, 4.31; 95% CI, 1.8,10; P = .001), or 1 high-risk genotype (adjusted OR, 1.96; 95% CI, 1.1,3.4; P = .01). CONCLUSIONS. Polymorphisms of the inflammatory pathway genes MPO ,G463A and SOD2Ala16Val are associated with elevated pancreatic cancer risk. Oxidative stress may play an important role in pancreatic cancer carcinogenesis. Cancer 2008. © 2008 American Cancer Society. [source]

An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early-onset colorectal cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2009
Chih-Ching Yeh
Abstract Endothelial-derived nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), may play an important role in colorectal carcinogenesis. However, the putative contribution of common eNOS genetic polymorphisms to colorectal cancer risk remains unknown. We genotyped 3 polymorphisms of eNOS (T-786C, G894T, and intron4b/a) in 727 colorectal adenocarcinoma cases and 736 age- and sex-matched healthy controls in Taiwan. Genotypes of the T-786C and G894T polymorphisms were determined by fluorescence polarization assays and the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 (intron4b/a) was analyzed by PCR. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among younger participants (,60 yrs), the intron4a variant genotype was associated with a significantly increased risk of colorectal cancer, compared with the intron4bb genotype (OR = 1.60, 95% CI = 1.04,2.46). In addition, those young individuals bearing a greater number of high-risk genotypes (OR > 1, i.e., CT+TT for T-786C, ba+aa for intron4b/a, and GG for G894T) of eNOS had a higher colorectal cancer risk (ptrend = 0.039). Compared with younger individuals without any putative high-risk genotypes, those with 3 high-risk genotypes had a significantly greater cancer risk (OR = 1.89, 95% CI = 1.04,3.43). Our results suggest that the eNOS intron4b/a polymorphism may contribute to early-onset colorectal cancer risk in the Taiwanese population. © 2008 Wiley-Liss, Inc. [source]

Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma

Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol- O -methyltransferase are associated with familial prostate carcinoma risk in a Japanese population

CANCER, Issue 7 2003
Kazuhiro Suzuki M.D.
Abstract BACKGROUND Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen-related enzymes and receptors and the risk of developing familial prostate carcinoma. METHODS In the current study, 101 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 114 healthy age and residence-matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol- O -methyltransferase (COMT) genes were analyzed. RESULTS For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97,5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02,3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85,2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high-grade carcinoma (OR, 2.59; 95% CI, 1.47,4.46; P = 0.048). The number of high-risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72,5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61,10.99; P = 0.002). CONCLUSIONS Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11639 [source]

Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis

CANCER SCIENCE, Issue 6 2006
Mostafa Saadat
The association between glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk has been both confirmed and refuted in a number of published studies. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published up to August 2005 to obtain more precise estimates of gastric cancer risk associated with GSTT1 polymorphism. In the present study, 16 case-control studies (with a total of 6717 subjects) were eligible for meta-analysis. There was no evidence of heterogeneity between the studies. The GSTT1 null genotype conferred a 1.06-fold increased risk of gastric cancer, which was not significant (95% confidence interval [CI]: 0.94,1.19). However, in the analysis of ethnic groups, we observed distinct differences associated with GSTT1 status. Restricting analyses to ethnic groups, the pooled odd ratios for the GSTT1 genotype were 1.27 in Caucasians (95% CI: 1.03,1.57) and 0.98 in Asians (95% CI: 0.86,1.13). Glutathione S-transferase M1 (GSTM1) and GSTT1 are involved in detoxification of a variety of compounds, some that overlap between enzymes and some that are highly specific. To investigate whether the profile of glutathione S-transferase genotypes was associated with risk of gastric cancer, further analyses combining the GSTT1 and GSTM1 genotypes were also carried out. There was a significant trend in risk associated with zero, one and two putative high-risk genotypes (,2 = 9.326, d.f. = 1, P = 0.0023). Those who had null genotypes of GSTM1 and GSTT1 had an increased gastric cancer risk compared with those who had both active genes (odds ratio = 2.08, 95% CI: 1.42,3.10). (Cancer Sci 2006; 97: 505,509) [source]