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Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans.

Publication ,  Journal Article
Walsh, KM; Gorlov, IP; Hansen, HM; Wu, X; Spitz, MR; Zhang, H; Lu, EY; Wenzlaff, AS; Sison, JD; Wei, C; Lloyd, SM; Chen, W; Frazier, ML ...
Published in: Cancer Epidemiol Biomarkers Prev
February 2013

BACKGROUND: Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31, and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans and refined previous association signals by using the reduced linkage disequilibrium observed in African-Americans. METHODS: 1,308 African-American cases and 1,241 African-American controls from 3 centers were genotyped for 760 single-nucleotide polymorphisms (SNP) spanning 3 regions, and additional SNP imputation was carried out. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate. RESULTS: The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution [rs16969968: OR, 1.57; 95% confidence interval (CI), 1.25-1.97; P, 1.1 × 10(-4)) and variants in the 5'-UTR. Associations on 6p22.1-p21.31 were histology specific and included a missense variant in BAT2 associated with squamous cell carcinoma (rs2736158: OR, 0.64; 95% CI, 0.48-0.85; P, 1.82 × 10(-3)). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR, 0.82; 95% CI, 0.73-0.93; P, 1.1 × 10(-3)). This association was stronger among cases with adenocarcinoma (OR, 0.75; 95% CI, 0.65-0.86; P, 8.1 × 10(-5)). CONCLUSIONS: Polymorphisms in 5p15.33, 6p22.1-p21.31, and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only with squamous cell carcinoma. IMPACT: Results implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

February 2013

Volume

22

Issue

2

Start / End Page

251 / 260

Location

United States

Related Subject Headings

  • Telomerase
  • Small Cell Lung Carcinoma
  • Risk Factors
  • Receptors, Nicotinic
  • Proteins
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Nerve Tissue Proteins
  • Middle Aged
 

Citation

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Walsh, K. M., Gorlov, I. P., Hansen, H. M., Wu, X., Spitz, M. R., Zhang, H., … Amos, C. I. (2013). Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans. Cancer Epidemiol Biomarkers Prev, 22(2), 251–260. https://doi.org/10.1158/1055-9965.EPI-12-1007-T
Walsh, Kyle M., Ivan P. Gorlov, Helen M. Hansen, Xifeng Wu, Margaret R. Spitz, Huifeng Zhang, Emily Y. Lu, et al. “Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans.Cancer Epidemiol Biomarkers Prev 22, no. 2 (February 2013): 251–60. https://doi.org/10.1158/1055-9965.EPI-12-1007-T.
Walsh KM, Gorlov IP, Hansen HM, Wu X, Spitz MR, Zhang H, et al. Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans. Cancer Epidemiol Biomarkers Prev. 2013 Feb;22(2):251–60.
Walsh, Kyle M., et al. “Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans.Cancer Epidemiol Biomarkers Prev, vol. 22, no. 2, Feb. 2013, pp. 251–60. Pubmed, doi:10.1158/1055-9965.EPI-12-1007-T.
Walsh KM, Gorlov IP, Hansen HM, Wu X, Spitz MR, Zhang H, Lu EY, Wenzlaff AS, Sison JD, Wei C, Lloyd SM, Chen W, Frazier ML, Seldin MF, Bierut LJ, Bracci PM, Wrensch MR, Schwartz AG, Wiencke JK, Amos CI. Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans. Cancer Epidemiol Biomarkers Prev. 2013 Feb;22(2):251–260.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

February 2013

Volume

22

Issue

2

Start / End Page

251 / 260

Location

United States

Related Subject Headings

  • Telomerase
  • Small Cell Lung Carcinoma
  • Risk Factors
  • Receptors, Nicotinic
  • Proteins
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Polymerase Chain Reaction
  • Nerve Tissue Proteins
  • Middle Aged