Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis

Abstract

The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated.For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS).The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage-and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods.None of the investigated polymorphisms modified response significantly in the whole patient population.However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele.In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.

Influence of single nucleotide polymorphisms in the MMP1 promoter region on cutaneous melanoma progression

“…For example, −1607 1G/2G was significantly associated with disease-free or overall survivals in patients with epithelial ovarian cancer [24], colorectal cancer [13]. However, the significant association was not found in breast cancer [18], esophageal adenocarcinoma [17] and lung cancer [25]. In the present study, we did not observe significant association of this variant with melanoma overall survival and the six clinicopathologic factors.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Furthermore, MMP-2 strongly contributes to prostate carcinogenesis (Littlepage et al, 2010) and in the vast majority of cases MMP-2 up-regulation is associated to poor prognosis (Offersen et al, 2010;Zhong et al, 2008). MMP-2 and cancer further registers a validation from genetic and epigenetic factors, since polymorphisms (SNPs) in the MMP-2 gene directly correlates with the pathology (Chaudhary et al, 2010;Kang et al, 2011;Scherf et al, 2010).…”

Matrix metalloproteinases: protective roles in cancer

“…An SNP analysis of eight SNPs in six genes ( MMP1 , MMP2 , MMP3 , MMP7 , MMP9 , MMP12 ) revealed that small cell lung cancer patients carrying the G allele of the –82A/G MMP12 polymorphism, which is associated with a higher gene expression in reporter gene assays [74], had a significantly prolonged overall survival compared to patients with the common allele [75]. Based on the aforementioned findings, we can conclude that the role of MMP‐12 in cancer is as yet not fully understood.…”