Functional polymorphisms in the promoter regions of MMP2 and MMP3 are not associated with melanoma progression

<p>Abstract</p> <p>Background</p> <p>The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.</p> <p>Methods</p> <p>We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.</p> <p>Results</p> <p>All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.</p> <p>Conclusion</p> <p>This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.</p

Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma

BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis

Tagging sentinel lymph nodes: a study of 100 patients with breast cancer

International audienc

[PP. 27.24] DIAGNOSTIC ACCURACY AND DIAGNOSTIC GAIN OF CRITERIA TO INTERPRET UNILATERALLY SELECTIVE ADRENAL VEIN SAMPLING (AVS) RESULTS

Objective: 10–20% of AVS performed in Excellence centers for primary aldosteronism (PA) are not bilaterally selective. The ratio of cortisol-corrected aldosterone concentration between adrenal vein and inferior vena cava (unilateral ratio, UR) has been proposed to interpret unilaterally selective AVS [1]:UR&lt;0.5could suggest unilateral PA on the opposite side; UR &gt;5.5 could suggest unilateral PA on the same side, and UR 0.5–5.5 would be inconclusive. Design and method: This retrospective study evaluates the diagnostic value of the UR on AVS data collected over10 years in a referral centre. French AVS-consensus criteria (selectivity index &gt;2, lateralisation ratio &gt;4) were used for AVS interpretation. We first assessed the numbers of cases with left and right UR both &lt;0.5 or both &gt;5.5, because in these cases the interpretation of unilaterally selective AVS will depend only on the side of successful adrenal vein cannulation, not on the side of the disease. We then assessed the sensitivity, specificity and PPV of these criteria for the diagnosis of unilateral PA. Cases with left and right UR both &lt;0.5 or both &gt;5.5 were counted as false positives for these calculations. We finally assessed the diagnostic impact of using the unilateral criteria in case of unilaterally selective AVS. Results: -537AVS were performed from 2001–2010, 64(12%) were not bilaterally selective using the reference criteria (28unilaterally selective and 36 bilaterally non-selective), 287 (53%) were diagnostic of bilateral PA, 99 (18%) of left PA and 87 (16%) of right PA [Table 1]. -Among 473 bilaterally selective AVS, 7 (1.5%) had left and right UR both &lt;0.5 and 32 (7%) had left and right UR both &gt;5.5 [Table 2]. -Sensitivity of UR &lt;0.5 to detect unilateral PA was 55%, specificity 91%, PPV79%. -Sensitivity of UR &gt;5.5 was 51%, specificity71%, PPV53% [Table3]. -Using these criteria to interpret 28 unilaterally selective AVS led to diagnose 2right PA but 0left PA with a contralateral UR &lt;0.5, 10 right PA and 6left PA with an ipsilateral UR &gt;5.5, the remaining 10 cases staying inconclusive. However, among the 16 unilateral PA diagnosed with an ipsilateral UR &gt;5.5, we must expect 8 false positives