International Agency for Research on Cancer, Lyon, France.
Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10(-16)), 6p21 (P = 2.3 × 10(-14)) and 15q25 (P = 2.2 × 10(-63)). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL; rs1333040, P = 3.0 × 10(-7)) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10(-8)). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer.
最近的全基因组关联研究（GWAS）已经确定了与肺癌风险相关的常见遗传变异，位于 5p15.33、6p21-6p22 和 15q25.1。其他一些遗传区域，包括 CHEK2（22q12）、TP53BP1（15q15）和 RAD52（12p13）的变体，已经在候选或途径分析中证明影响肺癌风险。为了确定肺癌的新风险变体，我们对 16 项 GWAS 进行了荟萃分析，总共包括 14900 例欧洲血统的病例和 29485 例对照。我们的数据为以前在 5p15（P=7.2×10(-16)）、6p21（P=2.3×10(-14)）和 15q25（P=2.2×10(-63)）位置上确定的风险位点提供了更多支持。此外，我们证明了 5p15、6p21 和 12p13 位点的组织学特异性效应，但 15q25 区域没有。亚组分析还确定了 9p21 上的一个新的鳞状细胞癌疾病位点（CDKN2A/p16(INK4A)/p14(ARF)/CDKN2B/p15(INK4B)/ANRIL；rs1333040，P=3.0×10(-7)），在一系列 5415 名汉族人（P=0.03；综合分析，P=2.3×10(-8)）中得到了复制。这项大型分析为遗传性遗传易感性在肺癌中的作用提供了额外的证据，并深入了解了不同组织学类型肺癌发展过程中的生物学差异。
