Role of chronic obstructive pulmonary disease in lung cancer pathogenesis

Table 1 Examples of genetic regions relevant to increased susceptibility to both chronic obstructive pulmonary disease and lung cancer

Chromosomal region	Possible gene(s)	Ref.
2q	GSS	[23]
4q31	HHIP, GYPA	[21]
5q33	HTR4, ADAM19	[21]
6p	GCLCL	[23]
6q	SMOC2	[22,24,25]
10q	GSTO2	[23]
11p	MMP1, MMP12, RRM1	[23,26]
12p	GSTM1	[27,28]
15q25	CHRNA3-5, IREB2	[21]
19q	ERCC1	[23]

Table 2 Oxidative stress genes with good evidence that they contribute to both chronic obstructive pulmonary disease and lung cancer

Gene	Polymorphism	COPD risk	Lung cancer risk	Ref.
EPHX1	Rs2234922 (A139G) and haplotypes	↑Asians ↔ Caucasians	↑	[88,89]
GSTM1	Null genotype	↑	↑	[28,90]
SOD3	Rs1799896	↑	In vitro evidence of SOD3 ↑risk	[90-92]

COPD: Chronic obstructive pulmonary disease; EPHX1: Epoxide hydrolase; GSTM1: Glutathione S-transferase M1; SOD3: Superoxide dismutase 3.

Table 3 Signalling pathways common to chronic obstructive pulmonary disease and lung cancer

Signal pathway	Downstream effects	Role in COPD	Role in lung cancer	Ref.
NFκβ	↑MMPs, ↑TNFα, ↓apoptosis, ↑angiogenesis	↑inflammation	↑cell proliferation, ↓cell death, metastasis	[111]
PI3K	Activation and migration of leukocytes	↑inflammation	↑cell proliferation, ↓cell death	[112,113]
P38 MAPK	Block JNK/c-Jun, ↑TNFα	↑inflammation	Metastasis, ↓cell death	[114]
PPARγ	↓MMP9, ↓TNFα, ↓TGFβ	↓inflammation	↑cell differentiation, ↓cell proliferation	[115,116]

COPD: Chronic obstructive pulmonary disease; MMPs: Matrix-metalloproteinases; JNK: c-Jun N-terminal kinases; TNFα: Tumour necrosis factor alpha; TGFβ: Tissue growth factor beta.