The Contribution of MMP-7 Genotypes to Colorectal Cancer Susceptibility in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) play important roles in inflammation and carcinogenesis, but the genotypic role of MMP-7 has never been investigated in colorectal cancer (CRC) among the Taiwanese. Therefore, in this study we aimed to evaluate the contribution of MMP-7 genotypes to the risk of CRC in Taiwan. MATERIALS AND METHODS: In this case-control study, MMP-7 A-181G and C-153T promoter genotypes were determined and their association with CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. In addition, the interaction of MMP-7 genotypes and personal behaviors were also examined. RESULTS: The percentages of variant AG and GG for MMP-7 A-181G genotypes were 10.5% and 1.7% in the CRC group and 11.9% and 2.2% in the control group, respectively (p for trend=0.7145). The allelic frequency distribution analysis showed that the variant G allele of MMP-7 A-181G conferred a slight but non-significant decreased CRC susceptibility to the wild-type C allele (odds ratio (OR)=0.86, 95% confidence interval (CI)=0.64-1.31, p=0.37). Taiwanese all harbour the CC genotype at MMP-7 C-153T. As for the gene-lifestyle interaction, there were no obvious joint effects of MMP-7 A-181G genotype on the risk of CRC among ever smoker, alcohol drinker, non-smoker or non-drinker subgroups. No statistically significant correlation was observed between MMP-7 A-181G genotypic distributions and age, gender, tumor size, location or metastasis status. CONCLUSION: The genotypes of MMP-7 A-181G may play an indirect role in determining personal susceptibility to CRC and prognosis. The further genotyping work on MMP-7 and other genes (such as other MMPs, oncogenes and tumor suppression genes) on CRC susceptibility and prognosis, should be taken into consideration spontaneously in the precision medicine era.

Contribution of matrix metalloproteinases-1 genotypes to gastric cancer susceptibility in Taiwan.

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.

The Contribution of Excision Repair Cross-complementing Group 1 Genotypes to Colorectal Cancer Susceptibility in Taiwan.

AIM: To evaluate the contribution of ERCC1 rs11615 and rs3212986 genotypes regarding the risk of colorectal cancer (CRC) in Taiwan. MATERIALS AND METHODS: In this case-control study, ERCC1 rs11615 and rs3212986 genotypes and their interaction with consumption of cigarettes and alcohol in determining CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. RESULTS: The percentages of CC, CT and TT for ERCC1 rs11615 genotype were 44.2%, 36.2% and 19.6% in the CRC group and 49.7%, 38.4% and 11.9% in the control group, respectively (p for trend=0.0158). The allelic frequency distribution analysis showed that the variant T allele of ERCC1 rs11615 conferred increased CRC susceptibility to the wild-type C allele (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.08-1.67, p=0.0079). As for the gene-lifestyle interaction, there were obvious joint effects of ERCC1 rs11615 genotype on the risk of CRC among ever smokers and alcohol drinkers, but not non-smokers or non-drinkers. There is a positive correlation of ERCC1 rs11615 genotype with lymph node metastasis, but not other CRC prognosis, including tumor size and location. CONCLUSION: ERCC1 rs11615 T allele serves as a predictive marker for CRC risk and future studies with larger samples and functional evaluation are warranted to validate these findings.

Contribution of Double-strand Break Repair Gene Nijmegen Breakage Syndrome 1 Genotypes, Gender Difference and Smoking Status to Taiwanese Lung Cancer.

BACKGROUND/AIM: Nijmegen breakage syndrome 1 (NBS1) is a component of MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and maintenance of chromosomal integrity. Failure in DNA damage response affects the level of cell survival, increases the frequency of gene mutation or chromosomal instability and other cellular phenotypic abnormalities, which are the important mechanisms of carcinogenesis. However, the contribution of variant NBS1 genotypes to lung cancer is not known. The current study aimed to evaluate the contribution of the common variant NBS1 Glu185Gln (rs1805794, E185Q) genotypes to the risk of lung cancer. MATERIALS AND METHODS: The contributions of the NBS1 Glu185Gln genotypes to lung cancer risk were investigated among 358 patients with lung cancer and 716 age- and gender-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: GG, CG and CC NBS1 Glu185Gln genotype percentages were 45.2%, 43.9% and 10.9% in the patient group and 46.1%, 45.1% and 8.8% in the non-cancer control group, respectively (p for trend=0.5423). Analysis of allelic frequency distributions showed that the C allele of NBS1 Glu185Gln did not increase lung cancer susceptibility (p=0.4916). Interestingly, the CC genotypes at NBS1 Glu185Gln enhanced the risk of lung cancer among the males adjusted odds ratio (aOR)=1.85, 95% confidence interval (CI)=1.12-2.83 and among the smokers (aOR=1.76, 95% CI=1.09-2.64) but not among the females and non-smokers. CONCLUSION: The CC genotype of NBS1 Glu185Gln may increase lung cancer risk only for males and smokers and may serve as a practical marker for early detective and predictive purposes of lung cancer.

The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan.

BACKGROUND/AIM: Metalloproteinases (MMPs) are a family of proteases which have been shown to be overexpressed in various types of cancers. However, the contribution of MMP1 genotype to hepatocellular carcinoma (HCC) has not been well studied. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of HCC in Taiwan, where HCC incidence is relatively high in the world. MATERIALS AND METHODS: In this case-control study, MMP1 genotype and its interaction with consumption of cigarettes and alcohol in determining HCC risk was investigated among 298 HCC patients and 889 age- and gender-matched healthy controls. RESULTS: The percentages of ever smokers and ever alcohol drinkers were much higher in the case group than in the control group. The percentages of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype were 37.2%, 38.3% and 24.5% in the HCC group and 34.8%, 44.0% and 21.2% in the control group, respectively (p for trend=0.2048). The allelic frequency distribution analysis showed the variant 1G allele of MMP1 promoter 1607 conferred similar HCC susceptibility as the wild-type 2G allele (odds ratio (OR)=1.01, 95% confidence interval (CI)=0.84-1.22, p=0.8735). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G allele on the risk of HCC among non-smokers, but not non-smokers, even alcohol drinkers or non-drinkers. CONCLUSION: The 1G allele of MMP1 promoter 1607 may have a protective effect on HCC risk for non-smokers in Taiwan and further validations are needed in other population groups.

Contribution of Matrix Metallopeptidase-1 Genotypes, Smoking, Alcohol Drinking and Areca Chewing to Nasopharyngeal Carcinoma Susceptibility.

BACKGROUND/AIM: The up-regulation of matrix metalloproteinase-1 (MMP-1) has been demonstrated to be correlated with lymph node metastasis of nasopharyngeal carcinoma (NPC); however, the genotypic role of MMP-1 is not well understand. The present study aimed to assess the contribution of MMP-1 promoter -1607 genotypes, combined with environmental carcinogens, on the predisposition to NPC tumorigenesis. MATERIALS AND METHODS: The MMP-1 promoter -1607 genotypes were examined for 352 age- and gender-matched controls and 176 NPC patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: We found that the MMP-1 promoter -1607 heterozygous 1G/2G and homozygous 1G/1G genotypes, were more and more prone to be associated with NPC risk (odds ratio (OR)=0.64 and 0.63, 95% confidence interval (CI)=0.43-1.03 and 0.36-0.96, p=0.0659 and 0.0932, respectively). In the dominant models, there was a significant association between the genotype of MMP-1 promoter -1607 and NPC risk (OR=0.64, 95% CI=0.43-0.91, p=0.0359). In addition, individuals carrying the 1G allele at MMP-1 promoter -1607 were less susceptible to NPC (OR=0.73; 95%CI=0.59 to 0.96, p=0.0418) after adjustment for age, gender, cigarette, alcohol and areca consumption. CONCLUSION: The 1G/1G genotype of MMP-1 promoter -1607 may independently have a protective effect on NPC risk, without interaction with behavioral factors, including cigarette, alcohol and areca consumption.

Matrix Metalloproteinase-1 Genetic Polymorphism in Breast Cancer in Taiwanese.

AIM: Metalloproteinases (MMPs) are a family of enzymes involved in many physiological processes, such as skeletal development, wound healing, and scar formation, as well as carcinogenesis. However, the contribution of MMP1 genotype to breast cancer has not been elucidated. This study aimed to evaluate the contribution of commonly studied MMP1 promoter 1607 genotype to breast cancer risk. MATERIALS AND METHODS: In this hospital-based case-control study, contribution of MMP1 genotype to breast cancer risk was evaluated among 1,232 patients with breast cancer and 1,232 gender-matched healthy controls. RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype was 36.0%, 41.3% and 22.7% in the breast cancer group and 34.2%, 44.5% and 21.3% in the non-cancer group, respectively (p for trend=0.2820). We also analyzed the allelic frequency distributions and found that the variant 1G allele of MMP1 promoter 1607 conferred similar breast cancer susceptibility as the wild-type 2G allele (odds ratio=0.99, 95% confidence interval=0.89-1.11, p=0.8858). There was no interaction between MMP1 promoter 1607 genotype and cigarette smoking or alcohol drinking habits. CONCLUSION: The genotype of MMP1 promoter 1607 may not be a major determining factor for breast cancer risk. The contribution of MMP1 promoter 1607 genotype to prognosis and subtypes of breast cancer needs further investigation.