RESUMO
Expression of matrix metalloproteinase-1 (MMP1), an interstitial collagenase regulating the extracellular matrix, plays a major role in carcinogenesis of gastric cancer, a leading cause of death worldwide. In literature, the single-nucleotide polymorphism (SNP) promoter -1607 1G/2G (rs1799750) at the MMP1 gene promoter has been reported to alter its own transcription level. While the importance's of the genotype of MMP1 promoter -1607 has not yet been studied in gastric cancer in Taiwan, our aim was to investigate MMP1 promoter -1607 genotypes and gastric cancer (GC) susceptibility in central Taiwan population. In the current hospital-based case-control study, the contribution of MMP1 promoter -1607 genotypes to GC risk was investigated among 121 GC patients and 363 gender- and age-matched healthy controls recruited and genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology. We found that the genotypic and allelic frequencies were not differentially distributed between GC patient and control groups. The variant 1G containing genotypes have interactions with cigarrete smoking behaviors and Helicobacter pylori infection status, but not alcoholism on GC susceptibility determination. Our findings suggest that the variant 1G allele on MMP1 promoter -1607 may contribute to GC carcinogenesis and may be useful for GC early detection and prevention when combined with cigarrete smoking behaviors and Helicobacter pylori infection status.
RESUMO
Interleukin-10 (IL10) is an immunosuppressive cytokine which may facilitate carcinogenesis by down-regulating interferon-gamma production and supporting tumor escape from the immune response. Polymorphisms within the promoter of IL10 gene may not only contribute to differential IL10 expression levels among individuals but also to oral cancer susceptibility. In this hospital-based study, the association of IL10 A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872) polymorphisms with oral cancer risk were examined. A total of 788 cases with oral cancer risk and 956 controls were genotypes and analyzed by polymerase chain reaction and restriction fragment length polymorphism. The results showed that there were significant differential distributions among oral cancer cases and controls in the genotypic (p=6.29×10(-11)) and allelic (p=2.80×10(-13)) frequencies of IL10 A-1082G. Individuals who carried the AG or GG genotype for IL10 A-1082G had a 1.90- and 3.27-fold higher risk, respectively, of developing nasopharyngeal carcinoma compared to those who carried AA genotype (95% confidence interval=1.51-2.39 and 1.95-5.47). None of the other two polymorphisms investigated appear to affect cancer risk. In gene-lifestyle interaction analysis, we provide first evidence showing of an obvious joint effect of IL10 A-1082G genotype with individual smoking and areca chewing habits on nasopharyngeal carcinoma risk. The AG and GG genotypes of IL10 A-1082G, together with smoking and areca chewing habits, synergistically contribute to individual susceptibility for oral cancer.