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Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.
Machiela MJ, Hsiung CA, Shu XO, Seow WJ, Wang Z, Matsuo K, Hong YC, Seow A, Wu C, Hosgood HD, Chen K, Wang JC, Wen W, Cawthon R, Chatterjee N, Hu W, Caporaso NE, Park JY, Chen CJ, Kim YH, Kim YT, Landi MT, Shen H, Lawrence C, Burdett L, Yeager M, Chang IS, Mitsudomi T, Kim HN, Chang GC, Bassig BA, Tucker M, Wei F, Yin Z, An SJ, Qian B, Lee VH, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Kim JH, Gao YT, Tsai YH, Jung YJ, Guo H, Hu Z, Hutchinson A, Wang WC, Klein RJ, Chung CC, Oh IJ, Chen KY, Berndt SI, Wu W, Chang J, Zhang XC, Huang MS, Zheng H, Wang J, Zhao X, Li Y, Choi JE, Su WC, Park KH, Sung SW, Chen YM, Liu L, Kang CH, Hu L, Chen CH, Pao W, Kim YC, Yang TY, Xu J, Guan P, Tan W, Su J, Wang CL, Li H, Sihoe AD, Zhao Z, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Kohno T, Kweon SS, Chen CY, Vermeulen RC, Wu J, Lim WY, Chen KC, Chow WH, Ji BT, Chan JK, Chu M, Li YJ, Yokota J, Li J, Chen H, Xiang YB, Yu CJ, Kunitoh H, Wu G, Jin L, Lo YL, Shiraishi K, Chen YH, Lin HC, Wu T, Wong MP, Wu YL, Yang PC, Zhou B, Shin MH, Fraumeni JF, Zheng W, Lin D, Chanock SJ, Rothman N, Lan Q
(2015) Int J Cancer 137: 311-9
MeSH Terms: Adult, Aged, Asian Continental Ancestry Group, China, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hong Kong, Humans, Japan, Lung Neoplasms, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Republic of Korea, Risk Factors, Singapore, Smoking, Taiwan, Telomere, Telomere Homeostasis
Show Abstract · Added April 3, 2018
Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.
Published 2014. This article is a US Government work and, as such, is in the public domain of the United States of America.
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Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.
Ng MC, So WY, Lam VK, Cockram CS, Bell GI, Cox NJ, Chan JC
(2004) Diabetes 53: 2676-83
MeSH Terms: Adult, Chromosome Mapping, Chromosomes, Human, Pair 1, Family, Female, Genetic Predisposition to Disease, Genome, Human, Hong Kong, Humans, Male, Metabolic Syndrome, Quantitative Trait Loci
Show Abstract · Added February 22, 2016
We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relative pairs) for variance component-based linkage analyses on seven MES-related traits: waist circumference, systolic and diastolic blood pressure (BP), triglyceride, HDL cholesterol, fasting plasma glucose, and insulin resistance index (insulin resistance index by homeostasis model assessment [HOMA%IR]). Analyses revealed three regions that showed suggestive linkage for MES and also showed overlapping signals for metabolic traits: chromosome 1 at 169.5-181.5 cM (logarithm of odds [LOD] = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic BP), chromosome 2 at 44.1-57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma glucose, and 1.29 for diastolic BP), and chromosome 16 at 45.2-65.4 cM (LOD = 1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that showed suggestive linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q, 9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C; and 6q for HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the chromosome 1 region to both MES and waist circumference (P(genome-wide) = 0.002 and 0.019, respectively). In summary, we have found a susceptibility locus on chromosome 1q21-q25 involved in the pathogenesis of multiple metabolic abnormalities, in particular obesity. Our results confirm the findings of previous studies on diabetes and related phenotypes. We also suggest the locations of other loci that may contribute to the development of MES in Hong Kong Chinese.
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Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.
Ng MC, So WY, Cox NJ, Lam VK, Cockram CS, Critchley JA, Bell GI, Chan JC
(2004) Diabetes 53: 1609-13
MeSH Terms: Asian Continental Ancestry Group, Chromosome Mapping, Chromosome Segregation, Chromosomes, Human, Pair 1, Computer Simulation, Diabetes Mellitus, Type 2, Genetic Linkage, Genetic Predisposition to Disease, Genome, Human, Hong Kong, Humans, Lod Score
Show Abstract · Added February 22, 2016
We conducted an autosomal genome scan to map loci for type 2 diabetes in a Hong Kong Chinese population. We studied 64 families, segregating type 2 diabetes, of which 57 had at least one member with an age at diagnosis of 0.59, P(pointwise) < 0.05): chromosome 1 at 173.9 cM (LOD = 3.09), chromosome 3 at 26.3 cM (LOD = 1.27), chromosome 4 at 135.3 cM (LOD = 2.63), chromosome 5 at 139.3 cM (LOD = 0.84), chromosome 6 at 178.9 cM (LOD = 1.91), chromosome 12 at 48.7 cM (LOD = 1.99), and chromosome 18 at 28.1 cM (LOD = 1.00). Simulation studies showed genome-wide significant evidence for linkage of the chromosome 1 region (P(genome-wide) = 0.036). We have confirmed the results of previous studies for the presence of a susceptibility locus on chromosome 1q21-q25 (173.9 cM) and suggest the locations of other loci that may contribute to the development of type 2 diabetes in Hong Kong Chinese.
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12 MeSH Terms