Table 5. Distribution of SNP genotypes in patients exhibiting progressive disease and partial response as the best response.
| Gene (a) | SNP ID | In patients with PD as their best response (n=10) | In patients with SD, PR or CR as their best response (n=78) | P-Value by Fisher's exact | Adjusted P-value by logistic regression | Odds ratio (95% CI) |
|---|---|---|---|---|---|---|
|
Genes involved in pharmacokinetics | ||||||
| ABCB1 | rs1045642 | CC 2/10 (20%) | CC 23/77 (30%) | NS | — | — |
| rs1128503 | TT 3/10 (30%) | TT 12/78 (15%) | NS | — | — | |
| rs2032582 | TT or TA 2/8 (25%) | TT or TA 10/72 (14%) | NS | — | — | |
| TCG copy | Not present 7/7 (100%) | Not present 54/70 (77%) | NS | — | — | |
| CYP3A5 | rs776746 | GG 8/8 (100%) | GG 61/67 (91%) | NS | — | — |
| NR1/2 | rs3814055 | TT 3/8 (38%) | TT 12/74 (16%) | NS | — | — |
| rs2276707 | TT 2/8 (25%) | TT 3/75 (4%) | 0.02 | NS | — | |
| NR1/3 | rs2307424 | CC 6/10 (60%) | CC 36/78 (46%) | NS | — | — |
| rs2307418 | AA 8/10 (80%) | AA 49/78 (63%) | NS | — | — | |
| rs4073054 | TT 7/10 (70%) | TT 31/78 (40%) | 0.08 | NS | — | |
| |
CAT copy |
Present 8/10 (80%) |
Present 40/77 (52%) |
0.09 |
NS |
— |
|
Genes involved in pharmacodynamics | ||||||
| PDGFRA | rs35597368 | TT 8/10 (80%) | TT 61/78 (78%) | NS | — | — |
| VEGFR2 | rs1870377 | TT 7/10 (70%) | TT 41/78 (53%) | NS | — | — |
| VEGFR3 | rs307821 | GT+TT 5/10 (50%) | GT+TT 18/78 (23%) | 0.07 | 0.05 | 5.763 (0.986–33.693) |
| |
rs307826 |
GA+GG 6/10 (60%) |
GA+GG 17/78 (22%) |
0.01 |
0.02 |
7.011 (1.372–42.209) |
|
Genes in alternative proangiogenic factors | ||||||
| FGFR2 | rs2981582 | TT 2/10 (20%) | TT 10/77 (13%) | NS | — | — |
| IL8 | rs4073 | AA 1/9 (11%) | AA 11/70 (16%) | NS | — | — |
Abbreviations: PR=partial response; PD=progressive disease; CR=complete response; SNP=single-nucleotide polymorphism; 95% CI=95% confidence interval; SD=stable disease; NS=nonsignificant.
The logistic regression analysis was adjusted for the presence of sarcomatoid dedifferentiation, the MSKCC score and baseline neutrophils.
Variants were combined as follows: ABCB1: a TCG copy was linked to better outcome in van der Veldt et al (2010). Therefore, we analysed the impact of CC in rs1045642, TT in rs1128503 and TT (or TA) in rs2032582; CYP3A5: the GG variant was linked to poor outcome in van der Veldt et al (2010); NR1/2 rs3814055 and rs2276707: the TT variant was linked to poor outcome in van der Veldt et al (2010); NR1/3: a CAT copy was linked to poor outcome in van der Veldt et al (2010). Therefore, we analysed the impact of CC in rs2307424, AA in rs2307418 and TT in rs4073054; FGFR2: the TT variant was linked to poor outcome in Xu et al (2011a, 2011b); IL8: the AA variant was linked to poor outcome in Xu et al (2011a, 2011b); PDGFRA: the TT variant was linked to poor outcome in van der Veldt et al (2010); VEGFR2: the TT variant was linked to poor outcome in van der Veldt et al (2010); VEGFR3 rs307821: the GT/TT variant was linked to poor outcome in Garcia-Donas et al (2011); VEGFR3 rs307826: the GA/GG variant was linked to poor outcome in Garcia-Donas et al (2011).