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. 2013 Apr 2;108(6):1378-86.
doi: 10.1038/bjc.2013.7. Epub 2013 Jan 29.

Common genetic variants in the 9p21 region and their associations with multiple tumours

F Gu  1 , R M Pfeiffer, S Bhattacharjee, S S Han, P R Taylor, S Berndt, H Yang, A J Sigurdson, J Toro, L Mirabello, M H Greene, N D Freedman, C C Abnet, S M Dawsey, N Hu, Y-L Qiao, T Ding, A V Brenner, M Garcia-Closas, R Hayes, L A Brinton, J Lissowska, N Wentzensen, C Kratz, L E Moore, R G Ziegler, W-H Chow, S A Savage, L Burdette, M Yeager, S J Chanock, N Chatterjee, M A Tucker, A M Goldstein, X R Yang
Affiliations

Common genetic variants in the 9p21 region and their associations with multiple tumours

F Gu et al. Br J Cancer. .

Abstract

Background: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers.

Methods: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction.

Results: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007).

Conclusion: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

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Figures

Figure 1
Figure 1
Linkage disequilibrium structures and genotype frequencies of rs3731239 among controls of Chinese (A) and Caucasian (B) samples. The LD (indicated by r2) maps were drawn using the Haploview software, based on the genotyping data of control samples for ESCC (A) and CA (B). LD patterns in other Caucasian studies were similar to that in CA.
See this image and copyright information in PMC

References

    1. ATBC Cancer Prevention Study Group The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol. 1994;4 (1:1–10. - PubMed
    1. Barrett JH, Iles MM, Harland M, Taylor JC, Aitken JF, Andresen PA, Akslen LA, Armstrong BK, Avril MF, Azizi E, Bakker B, Bergman W, Bianchi-Scarra G, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Corda E, Cust AE, Debniak T, Duffy D, Dunning AM, Easton DF, Friedman E, Galan P, Ghiorzo P, Giles GG, Hansson J, Hocevar M, Hoiom V, Hopper JL, Ingvar C, Janssen B, Jenkins MA, Jonsson G, Kefford RF, Landi G, Landi MT, Lang J, Lubinski J, Mackie R, Malvehy J, Martin NG, Molven A, Montgomery GW, van Nieuwpoort FA, Novakovic S, Olsson H, Pastorino L, Puig S, Puig-Butille JA, Randerson-Moor J, Snowden H, Tuominen R, Van Belle P, van der Stoep N, Whiteman DC, Zelenika D, Han J, Fang S, Lee JE, Wei Q, Lathrop GM, Gillanders EM, Brown KM, Goldstein AM, Kanetsky PA, Mann GJ, Macgregor S, Elder DE, Amos CI, Hayward NK, Gruis NA, Demenais F, Bishop JA, Bishop DT. Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet. 2011;43 (11:1108–1113. - PMC - PubMed
    1. Bartoletti R, Cai T, Nesi G, Roberta Girardi L, Baroni G, Dal Canto M. Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer. J Surg Res. 2007;143 (2:422–427. - PubMed
    1. Bhattacharjee S, Rajaraman P, Jacobs KB, Wheeler WA, Melin BS, Hartge P, Yeager M, Chung CC, Chanock SJ, Chatterjee N. A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits. Am J Hum Genet. 2012;90 (5:821–835. - PMC - PubMed
    1. Bishop DT, Demenais F, Iles MM, Harland M, Taylor JC, Corda E, Randerson-Moor J, Aitken JF, Avril MF, Azizi E, Bakker B, Bianchi-Scarra G, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Chin AWT, Debniak T, Galore-Haskel G, Ghiorzo P, Gut I, Hansson J, Hocevar M, Hoiom V, Hopper JL, Ingvar C, Kanetsky PA, Kefford RF, Landi MT, Lang J, Lubinski J, Mackie R, Malvehy J, Mann GJ, Martin NG, Montgomery GW, van Nieuwpoort FA, Novakovic S, Olsson H, Puig S, Weiss M, van Workum W, Zelenika D, Brown KM, Goldstein AM, Gillanders EM, Boland A, Galan P, Elder DE, Gruis NA, Hayward NK, Lathrop GM, Barrett JH, Bishop JA. Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet. 2009;41 (8:920–925. - PMC - PubMed

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