Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by A Risch
Total Records ( 3 ) for A Risch
  M. N Timofeeva , S Kropp , W Sauter , L Beckmann , A Rosenberger , T Illig , B Jager , K Mittelstrass , H Dienemann , Bartsch The LUCY Consortium , H Bickeboller , J. C Chang Claude , A Risch and H. E. Wichmann
 

Cytochrome P450 (CYP) enzymes, involved in metabolism of tobacco carcinogens, are also involved in estrogen metabolism and many are regulated by estrogens. These genes may thus be of relevance to gender-specific differences in lung cancer risk, particularly in early-onset lung cancer, where a high proportion of women is observed. We conducted a case–control study to investigate genetic polymorphisms in cytochromes that might modify the risk of developing early-onset lung cancer. In total, 638 Caucasian patients under the age of 51 with primary lung cancer and 1300 cancer-free control individuals, matched by age and sex, were included in this analysis. Thirteen polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analyzed. No significant association was found for any of the analyzed polymorphisms and lung cancer risk overall. However, among women, a significantly increased risk of early-onset lung cancer was observed for carriers of the minor allele of CYP1B1 SNP rs1056836 [odds ratio (OR) 1.97; 95% confidence interval (CI) 1.32–2.94; P < 0.001]. Also, a non-significant increase in lung cancer risk was observed in the group of women carriers of the minor allele of CYP2A13 SNP rs1709084 (OR 1.64; 95% CI 1.00–2.70; P = 0.05). The effect of these two polymorphisms was shown to be modified by smoking. Haplotype analysis was performed for CYP1B1 and CYP2A13. No differences between cases and controls were observed for both genes (P = 0.63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women.

  T Truong , W Sauter , J. D McKay , H. D Hosgood , C Gallagher , C. I Amos , M Spitz , J Muscat , P Lazarus , T Illig , H. E Wichmann , H Bickeboller , A Risch , H Dienemann , Z. F Zhang , B. P Naeim , P Yang , S Zienolddiny , A Haugen , L Le Marchand , Y. C Hong , J. H Kim , E. J Duell , A. S Andrew , C Kiyohara , H Shen , K Matsuo , T Suzuki , A Seow , D. P. K Ng , Q Lan , D Zaridze , N Szeszenia Dabrowska , J Lissowska , P Rudnai , E Fabianova , V Constantinescu , V Bencko , L Foretova , V Janout , N. E Caporaso , D Albanes , M Thun , M. T Landi , J Trubicka , M Lener , J Lubinski , Wang EPIC lung , A Chabrier , P Boffetta , P Brennan and R. J. Hung
 

Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10–4). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89–0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85–0.95), P = 1 x 10–4]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.

  T Truong , R. J Hung , C. I Amos , X Wu , H Bickeboller , A Rosenberger , W Sauter , T Illig , H. E Wichmann , A Risch , H Dienemann , R Kaaks , P Yang , R Jiang , J. K Wiencke , M Wrensch , H Hansen , K. T Kelsey , K Matsuo , K Tajima , A. G Schwartz , A Wenzlaff , A Seow , C Ying , A Staratschek Jox , P Nurnberg , E Stoelben , J Wolf , P Lazarus , J. E Muscat , C. J Gallagher , S Zienolddiny , A Haugen , H. F. M van der Heijden , L. A Kiemeney , D Isla , J. I Mayordomo , T Rafnar , K Stefansson , Z. F Zhang , S. C Chang , J. H Kim , Y. C Hong , E. J Duell , A. S Andrew , F Lejbkowicz , G Rennert , H Muller , H Brenner , L Le Marchand , S Benhamou , C Bouchardy , M. D Teare , X Xue , J McLaughlin , G Liu , J. D McKay , P Brennan and M. R. Spitz
  Background

Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies.

Methods

Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case–control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided.

Results

Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 x 10–26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 x 10–10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 x 10–8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 x 10–5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer.

Conclusions

In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility