Genetic variants in the nucleotide excision repair genes are associated with the risk of developing endometriosis.

Endometriosis is a major health issue among women of reproductive age. However, its etiology has not yet been completely understood. We investigated 10 single nucleotide polymorphisms from six novel nucleotide excision repair genes and the susceptibility to endometriosis. A total of 153 patients with endometriosis were recruited during 2000-2010 from central Taiwan. Pathological confirmation was necessary for all patients, and exclusion criteria included the presence of leiomyoma, adenomyosis, or cancer of the uterine, cervix, or ovary and a prescription of hormone therapy. Furthermore, a total of 636 age-matched individuals without endometriosis were recruited during the same time period from central Taiwan. The polymerase chain reaction coupled with restriction fragment length polymorphism methodology was applied for genotyping. The multivariate logistic regression analysis showed that subjects carrying the ERCC1 rs11615 TT (OR = 2.04, 95% CI = 1.36-3.41), ERCC2 rs1799793 AA (OR = 1.86, 95% CI = 1.14-3.11), and ERCC6 rs2228528 AA genotypes (OR = 1.79, 95% CI = 1.13-2.83) exhibited significantly increased risks of developing endometriosis compared with their counterparts carrying the wild-type genotypes. This study suggests that certain single nucleotide polymorphisms of nucleotide excision repair genes excision repair cross-complementation group 1 (ERCC1, ERCC2, and ERCC6) predispose women to the development of endometriosis.

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan.

BACKGROUND/AIM: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. MATERIALS AND METHODS: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. RESULTS: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. CONCLUSION: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

Contribution of Matrix Metalloproteinase-2 Promoter Genotypes to Nasopharyngeal Cancer Susceptibility and Metastasis in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase 2 (MMP2) is up-regulated in many cancers. However, the association of MMP2 genotype to nasopharyngeal cancer (NPC) susceptibility in Taiwan remains elusive. MATERIALS AND METHODS: In this study, the role of MMP2 promoter C-1306T (rs243865) and C-735T (rs2285053) genotypes were investigated among 208 NPC patients and 416 healthy controls, and their role in NPC staging and TNM classifications were examined. RESULTS: There was no differential distribution as for the genotypic or allelic frequencies at MMP2 promoter C-1306T or C-735T between the control and case groups. Noticeably, those with MMP2 C-1306T CT+TT genotypes had a lower metastatic risk than those with CC (p=0.0295). As for staging, T and N classifications, there was no differential distribution in C-1306T genotypes (p>0.05). Also, there was no differential distribution of C-735T genotypes according to different behavioral/clinicopathological characteristics. CONCLUSION: CT and TT genotypes at MMP2 C-1306T were associated with a significantly decreased risk of NPC metastasis.

Contribution of MMP2 Promoter Genotypes to Oral Cancer Susceptibility, Recurrence and Metastasis in Taiwan.

AIM: Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. MATERIALS AND METHODS: In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. RESULTS: The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). CONCLUSION: The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Association of Matrix Metalloproteinase-8 Genotypes with the Risk of Bladder Cancer.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) control the homeostasis of the extracellular matrix and their genetic polymorphisms may contribute to cancer susceptibility. The aim of this study was to reveal the genotypes of MMP8 among the Taiwanese and examine the contribution of MMP8 C-799T, Val436Ala and Lys460Thr polymorphisms to bladder cancer. MATERIALS AND METHODS: MMP8 C-799T, Val436Ala and Lys460Thr polymorphic genotypes were determined in 375 patients with bladder cancer and 375 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Regarding MMP8 C-799T, there was no significant differential distribution between patient and control groups [p for trend=0.6629]. The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at MMP8 C-799T were 1.13 (95%CI=0.89-1.44, p=0.3688) and 1.10 (95%CI=0.87-1.52, p=0.9030), respectively, compared to those carrying the wild-type CC genotype. Regarding MMP8 Val436Ala, there was no significant differential distribution between patient and control groups [p for trend=0.8166]. The adjusted OR for those carrying AC and CC genotypes at MMP8 Val436Ala were 0.71 (95%CI=0.31-2.28, p=0.6094) and 1.00 (95%CI=0.21-4.73, p=0.7247), respectively. The polymorphism Lys460Thr at MMP8 was not found among Taiwanese patients. CONCLUSION: MMP8 C-799T, Val436Ala and Lys460Thr may only play an indirect role in determining personal cancer susceptibility for bladder cancer in Taiwan.