Carcinogenesis Advance Access originally published online on March 25, 2009
Carcinogenesis 2009 30(5):793-798; doi:10.1093/carcin/bgp065
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Matrix metalloproteinase 1, 3 and 12 polymorphisms and esophageal adenocarcinoma risk and prognosis
1 Medical Oncology and Hematology, Biostatistics, Princess Margaret Hospital and Departments of Medicine, Medical Biophysics, Biostatistics and Epidemiology, Dalla Lama School of Public Health and University of Toronto, Ontario, Canada M5G 2M9
2 Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
3 Dana-Farber Cancer Institute, Boston, MA 02115, USA
4 Massachusetts General Hospital, Boston, MA 02114, USA
5 Toronto Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada M4N 3M5
6 Applied Molecular Oncology, Department of Medical Biophysics, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
* To whom correspondence should be addressed. Princess Margaret Hospital/Ontario Cancer Institute, 610 University Avenue, Suite 7-124, Toronto, Ontario M5G 2M9, Canada. Tel: +1 416 946 4501 ext. 3428; Fax: +1 416 946 6546; Email: geoffrey.liu{at}uhn.on.ca
The matrix metalloproteinase (MMP) family degrade extracellular matrix and mediate pathways including apoptosis, angiogenesis and immunity. We studied the association between four MMP polymorphisms within three MMP genes and esophageal adenocarcinoma (EA) risk and prognosis. A total of 313 EA cases and 455 age and gender frequency-matched controls were genotyped for MMP1 1G/2G, MMP3 6A/5A, MMP12 –82A/G and MMP12 1082A/G. The association between individual MMP polymorphisms and EA risk was evaluated using regression models and adjusted for age, gender, adult body mass index and smoking status. Haplotype analysis was performed to investigate the combined effect of all four linked MMP polymorphisms and EA risk. The MMP1 and MMP3 polymorphisms were associated with increased EA risk: MMP1 1G/2G and 2G/2G had adjusted odds ratios of 1.46 [95% confidence interval 1.0–2.1; P = 0.04] and adjusted odds ratio 1.83 (1.2–2.8; P = 0.005), respectively, whereas MMP3 6A/5A had adjusted odds ratio 1.40 (95% confidence interval 1.0–2.1; P = 0.09) and MMP3 5A/5A had 1.61 (95% confidence interval 1.0–2.5; P = 0.03). Two MMP haplotypes [MMP1–MMP3–MMP12 (–82) 2G-5A-A (adjusted odds ratio 1.36, 95% confidence interval 1.0–1.8; P = 0.03) and 2G-5A-G (adjusted odds ratio 1.70, 95% confidence interval 1.1–2.6; P = 0.01)] were also associated with increased EA risk. The relationship between BE cases with the same set of controls was similar. No association was identified between the MMP polymorphisms and overall survival or progression free survival of patients with EA. MMP1, MMP3 and possibly MMP12 –82A/G polymorphisms and their haplotypes are associated with increased EA risk.
Abbreviations: BMI, body mass index; EA, esophageal adenocarcinoma; GERD, gastroesophageal reflux disease; HWE, Hardy–Weinberg equilibrium; MMP, matrix metalloproteinase; OS, overall survival
Received August 20, 2008; revised February 17, 2009; accepted March 20, 2009.