Methods and compositions for assessment of pulmonary function and disorders

A method of determining a subject's risk of developing lung cancer, comprising analysing a sample from said subject for the presence of two or more polymorphisms., selected from the group consisting of:

• the Ser307Ser G/T polymorphism in the X-ray repair complementing defective repair in Chinese hamster cells 4 gene (XRCC4);
• R19W A/G in the gene encoding Cerberus 1 (Cer 1);
• K3326X A/T in the breast cancer 2 early onset gene (BRCA2);
• V433M A/G in the gene encoding Integrin alpha-11 (ITGA11);
• E375G T/C in the gene encoding Calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1);
• A/T c74delA in the gene encoding cytochrome P450 polypeptide CYP3A43;
• A/C (rs2279115) in the gene encoding B-cell CLL/lymphoma 2 (BCL2);
• A/G at +3100 in the 3′UTR (rs2317676) of the gene encoding Integrin beta 3;
• −3714 G/T (rs6413429) in the gene encoding Dopamine transporter 1 (DAT1);
• A/G (rs1139417) in the gene encoding Tumor necrosis factor receptor 1 (TNFR1);
• C/Del (rs1799732) in the gene encoding Dopamine receptor D2 (DRD2);
• C/T (rs763110) in the gene encoding Fas ligand (FasL);
• C/T (rs5743836) in the gene encoding Toll-like receptor 9 (TLR9):
• −81 C/T (rs 2273953) in the 5′ UTR of the gene encoding Tumor protein P73 (P73);
• and
• a polymorphism in linkage disequilibrium with any one or more of these polymorphisms.

A method of determining a human subject's risk of developing lung cancer, said method comprising the steps:

• (i) obtaining the result of one or more genetic tests of a sample from said subject;
• and
• (ii) analysing the result for the presence or absence of one or more polymorphisms, wherein said one or more polymorphisms comprises a genotype of AG or GG at +3100 in the 3′UTR (rs2137676) of the gene encoding Integrin beta 3 (ITGB3);
• wherein a result indicating the presence of said genotype is indicative of the subject's decreased risk of developing lung cancer.

A method of determining a subject's risk of developing lung cancer, comprising the analysis of two or more polymorphisms selected from the group consisting of:

• Ser307Ser G/T in the X-ray repair complementing defective repair in Chinese hamster cells 4 gene (XRCC4)
• R19W A/G in the gene encoding Cerberus 1 (Cer 1);
• K3326X A/T in the breast cancer 2 early onset gene (BRCA2);
• V433M A/G in the gene encoding Integrin alpha-11 (ITAG11);
• or
• E375G T/C in the gene encoding Calcium/calmodulin-dependent protein kinase kinase 1 (CAMKK1);
• A/T c74delA in the gene encoding cytochrome P450 polypeptide CYP3A43;
• A/C (rs2279115) in the gene encoding B-cell CLL/lymphoma 2 (BCL2);
• −3714 G/T (rs6413429) in the gene encoding Dopamine transporter 1 (DAT1);
• A/G (rs1139417) in the gene encoding Tumor necrosis factor receptor 1 (TNFR1);
• C/Del (rs1799732) in the gene encoding Dopamine receptor D2 (DRD2);
• C/T (rs763110) in the gene encoding Fas ligand (FasL);
• C/T (rs5743836) in the gene encoding Toll-like receptor 9 (TLR9);
• −81 C/T (rs 2273953) in the 5′ UTR of the gene encoding Tumor protein P73 (P73);
• and a polymorphism in linkage disequilibrium with any one or more of these polymorphisms.

A method of assessing a subject's suitability for an intervention diagnostic of or therapeutic for lung cancer, the method comprising:

• a) providing a net score for said subject, wherein the net score is or has been determined by:
• i) providing the result of one or more genetic tests of a sample from the subject, and analysing the result for the presence or absence of protective polymorphisms and for the presence or absence of susceptibility polymorphisms, wherein said protective and susceptibility polymorphisms are associated with lung cancer,
• ii) assigning a positive score for each protective polymorphism and a negative score for each susceptibility polymorphism or vice versa;
• iii) calculating a net score for said subject by representing the balance between the combined value of the protective polymorphisms and the combined value of the susceptibility polymorphisms present in the subject sample;
• and
• b) providing a distribution of net scores for lung cancer sufferers and non-sufferers wherein the net scores for lung cancer sufferers and non-sufferers are or have been determined in the same manner as the net score determined for said subject;
• and
• c) determining whether the net score for said subject lies within a threshold on said distribution separating individuals deemed suitable for said intervention from those for whom said intervention is deemed unsuitable;
• wherein a net score within said threshold is indicative of the subject's suitability for the intervention, and wherein a net score outside the threshold is indicative of the subject's unsuitability for the intervention.

A kit for assessing a subject's risk of developing one or more obstructive lung diseases selected from lung cancer, said kit comprising a means of analysing a sample from said subject for the presence or absence of one or more polymorphisms selected from the group consisting of:

• Ser307Ser G/T polymorphism in the X-ray repair complementing defective repair in Chinese hamster cells 4 gene (XRCC4);
• A/T c74delA in the gene encoding cytochrome P450 polypeptide CYP3A43;
• A/C (rs2279115) in the gene encoding B-cell CLL/lymphoma 2 (BCL2):
• A/G at +3100 in the 3′UTR (rs2317676) of the gene encoding Integrin beta 3 (ITGB3):
• −3714 G/T (rs6413429) in the gene encoding Dopamine transporter 1 (DAT1);
• A/G (rs1139417) in the gene encoding Tumor necrosis factor receptor 1 (TNFR1);
• C/Del (rs1799732) in the gene encoding Dopamine receptor D2 (DRD2);
• C/T (rs763110) in the gene encoding Fas ligand (FasL);
• C/T (rs5743836) in the gene encoding Toll-like receptor 9 (TLR9);
• and
• a polymorphism in linkage disequilibrium with one or more of these polymorphisms.