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Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer.

ABSTRACT: Four genome-wide association (GWA) studies have found that variation in a region of strong linkage disequilibrium on the long arm of chromosome 15 (15q24-25.1) containing nicotinic acetylcholine receptor genes contributes to lung cancer risk. Because cigarette smoking is a major risk factor for developing both lung cancer and pancreatic cancer, we hypothesized that variation in this region may also modify individual susceptibility to pancreatic cancer.We conducted a case-control study of 523 patients with pathologically confirmed pancreatic adenocarcinoma and 1046 age-, sex-, ethnicity-, and smoking behavior-matched cancer-free controls.We found that 2 risk single nucleotide polymorphisms reported in the lung cancer GWA studies-rs8034191: A>G and rs1051730: G>A, located in this 15q24-25.1 region-were not associated with risk of pancreatic cancer.The results of our study suggest that the 2 single nucleotide polymorphisms at 15q25.1 do not modify pancreatic cancer risk.

SUBMITTER: Chen J

PROVIDER: S-EPMC3138891 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer.

Chen Jinyun J Wu Xifeng X Pande Mala M Amos Christopher I CI Killary Ann M AM Sen Subrata S Frazier Marsha L ML

Pancreas 20110801 6

<h4>Objectives</h4>Four genome-wide association (GWA) studies have found that variation in a region of strong linkage disequilibrium on the long arm of chromosome 15 (15q24-25.1) containing nicotinic acetylcholine receptor genes contributes to lung cancer risk. Because cigarette smoking is a major risk factor for developing both lung cancer and pancreatic cancer, we hypothesized that variation in this region may also modify individual susceptibility to pancreatic cancer.<h4>Methods</h4>We conduc ...[more]

PMID: 21697764

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Project description:BackgroundThe association between polymorphisms on 15q25.1 and lung cancer has been widely evaluated; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two polymorphisms (CHRNA3 gene: rs1051730 and AGPHD1 gene: rs8034191) on 15q25.1.MethodsData were extracted from 15 and 14 studies on polymorphisms rs1051730 and rs8034191 involving 12301/14000 and 14075/12873 lung cancer cases/controls, respectively. The random-effects model was applied, addressing heterogeneity and publication bias.ResultsThe two polymorphisms followed Hardy-Weinberg equilibrium for all studies (P>0.05). For rs1051730-G/A, carriers of A allele had a 36% increased risk for lung cancer (95% confidence interval [CI]: 1.27-1.46; P<0.0005), without heterogeneity (P = 0.258) or publication bias (P(Egger) = 0.462). For rs8034191-T/C, the allelic contrast indicated that C allele conferred a 23% increased risk for lung cancer (95% CI: 1.08-1.4; P = 0.002), with significant heterogeneity (P<0.0005), without publication bias (P(Egger) = 0.682). Subgroup analyses suggested that the between-study heterogeneity was derived from ethnicity, study design, matched information, and lung cancer subtypes. For example, the association of polymorphisms rs1051730 and rs8034191 with lung cancer was heterogeneous between Caucasians (OR = 1.32 and 1.22; 95% CI: 1.25-1.44 and 1.05-1.42; P<0.0005 and 0.008, respectively) and East Asians (OR = 1.51 and 1.03; 95% CI: 0.76-3 and 0.47-2.27; P = 0.237 and 0.934, respectively) under the allelic model, and this association was relatively strengthened under the dominant model. There was no observable publication bias for both polymorphisms.ConclusionsOur findings demonstrated that CHRNA3 gene rs1051730-A allele and AGPHD1 gene rs8034191-T allele might be risk-conferring factors for the development of lung cancer in Caucasians, but not in East-Asians.

Dataset Information

Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer.

Publications

Susceptibility locus for lung cancer at 15q25.1 is not associated with risk of pancreatic cancer.

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