The Contribution of Matrix Metalloproteinase-1 Genotype to Oral Cancer Susceptibility in Taiwan.

AIM: Metalloproteinases (MMPs) are a family of multifunctional proteins which have been shown to be up-regulated in various types of cancer. However, the contribution of MMP1 genotype to oral cancer has not been elucidated. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of oral cancer. MATERIALS AND METHODS: In this case-control study, MMP1 genotype and its interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated in 788 patients with oral cancer and 956 gender-matched healthy controls. RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype was 36.8%, 40.2% and 23.0% in the oral cancer group and 34.3%, 44.9% and 20.8% in the non-cancer control group, respectively (p for trend=0.1454). We also analyzed the allelic frequency distributions and found that the variant 1G allele of MMP1 promoter 1607 conferred similar oral cancer susceptibility as the wild-type 2G allele (odds ratio=0.99, 95% confidence interval=0.87-1.14, p=0.9199). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G/2G genotype on the risk of oral cancer among smokers (odds ratio=0.71, 95% confidence interval=0.55-0.91, p=0.0076), but not non-smokers. There was no interaction between MMP1 promoter 1607 genotype and areca chewing or alcohol drinking habits. CONCLUSION: The 1G/2G genotype of MMP1 promoter 1607 may have a protective effect on oral cancer risk for smokers. The detailed mechanisms involved in this require further investigation.

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.

Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: It has been previously proposed that genetic variations on DNA repair genes confer susceptibility to cancer and the DNA repair gene Xeroderma Pigmentosum Group D (XPD) is thought to play the role of a helicase during excision repair and transcription. We investigated three genotypes of XPD, at promoter -114 (rs3810366), Asp312Asn (rs1799793) and Lys751Gln (rs13181), regarding their association with colorectal cancer susceptibility in a Taiwanese population. MATERIALS AND METHODS: In total, 362 patients with colorectal cancer and 362 gender- and age-matched healthy controls were genotyped by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP), and their XPD genotypes' association with colorectal cancer risk was investigated. RESULTS: The genotypes of XPD Asp312Asn (p=0.2493), Lys751Gln (p=0.7547) and promoter -114 (p=0.8702), were not associated with susceptibility for colorectal cancer. The Chi-square test revealed that the variant alleles of XPD Asp312Asn, Lys751Gln and promoter -114 was not associated with susceptibility for colorectal cancer either [p=0.1330, 0.3888 and 0.8740; odds ratio (OR)=1.20, 0.83 and 0.98; 95% confidence interval (95%CI)=0.95-1.52, 0.54-1.27 and 0.80-1.21, respectively]. The risk of A/G and A/A genotypes have no association with cancer risk among non-alcohol drinkers (OR=1.24, 95%, CI=0.90-1.72, p=0.2103) or alcohol drinkers (OR=1.51, 95% CI=0.64-3.55, p=0.4648). There exists no obvious contribution of XPD genotypes to tumor size (p=0.3531), location (p=0.3006) and lymph node metastasis (p=0.1061). CONCLUSION: Asp312Asn, Lys751Gln and promoter -114 of the XPD gene were not found to be adequate predictive markers for colorectal cancer risk in Taiwan.

The Role of IL-10 Promoter Polymorphisms in Renal Cell Carcinoma.

BACKGROUND/AIM: Renal cell carcinoma (RCC) accounts for approximately 3% of all cancer-related mortalities worldwide and the risk factors for the development of RCC have not yet been fully elucidated. Mounting proteomic evidence suggests that inflammatory process plays a role in RCC etiology and interleukin-10 (IL-10) is an important immunosuppressive cytokine. However, little is known on the contribution of IL-10 genotypes to RCC. This study aimed at evaluating the contribution of IL-10 promoter A-1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genetic polymorphisms to the risk of RCC in Taiwan. MATERIALS AND METHODS: Associations of the three IL-10 polymorphic genotypes with the risk of RCC were examined among 92 RCC patients and 580 age- and gender-matched cancer-free controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The pilot results showed that the percentages of TT and TC for IL-10 T-819C genotypes were significantly higher in the RCC patient group than those in the healthy control group. The CC genotype carriers were of lower risk for RCC (odds ratio (OR)=0.33, 95% confidence interval (CI)=0.12-0.93, p=0.0369). There is no difference in the distribution of A-1082G or A-592C genotype between the RCC and control groups. CONCLUSION: The CC genotype of IL-10 T-819C genotype may have a protective effect on RCC risk in Taiwan. Further investigation with larger sample size in addition to genotype-phenotype correlation and intracellular mechanisms are our future work.

Significant Association of Interleukin-10 Polymorphisms with Childhood Leukemia Susceptibility in Taiwan.

Mounting evidence supports the notion that inflammatory processes play a role in carcinogenesis, and interleukin-10 (IL10) is an important inflammatory cytokine. This study aimed to evaluate the contribution of IL10 A-1082G (rs1800896), T-819C (rs3021097) and A-592C (rs1800872) genotypes to the risk of childhood acute lymphoblastic leukemia (ALL) in Taiwan. Associations of these IL10 polymorphic genotypes with ALL risk were analyzed in 266 patients with childhood ALL patients and 266 non-cancer healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The results showed that CC genotype carriers at IL10 T-819C were at lower risk for childhood ALL (odds ratio=0.33, 95% confidence interval=0.16-0.68). On the contrary, AC and CC genotype carriers at IL10 A-592C were at higher risk for childhood ALL (odds ratio=1.73 and 6.34, 95% confidence interval=1.19-2.51 and 3.16-12.72, respectively). There was no difference in the distribution of A-1082G genotypes between childhood ALL and control groups. The genotypes at IL10 T-819C and A-592C may serve as predictive biomarkers for childhood ALL in Taiwan.

The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.

The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.

The Association of Flap Endonuclease 1 Genotypes with the Risk of Childhood Leukemia.

AIM: Flap endonuclease 1 (FEN1) is one of the most important proteins in maintaining genome stability and preventing carcinogenesis. In recent years, the contribution of two variants of FEN1, rs174538 and rs4246215, regarding cancer risk have been investigated in lung, breast, liver, esophageal, gastric, colorectal cancer and glioma. However, it has not been revealed whether rs174538 and rs4246215 are associated with leukemia. Therefore, in the present study we aimed to evaluate the contribution of these genotypic polymorphisms in FEN1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS: In total, 266 patients with childhood ALL and an equal number of recruited non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The FEN1 rs174538 genotype, but not rs4246215, was differently distributed between childhood ALL and control groups. The AG and AA of FEN1 rs174538 genotypes were significantly less frequently found in childhood ALL patients than in controls (odds ratio [OR]=0.68 and 0.48, 95%confidence intervals [CI]=0.47-0.98 and 0.24-0.82, respectively). As for gender, boys carrying the FEN1 rs174538 AG or AA genotype conferred lower ORs of 0.55 and 0.36 (95%CI=0.33-0.91 and 0.18-0.73, p=0.0053) for childhood ALL. Regarding age, those equal to or greater than 3.5 years of age at onset carrying the FEN1 rs174538 AG or AA genotype were of lower risk (ORs=0.53 and 0.32, 95%CI=0.31-0.90 and 0.15-0.70, p=0.0042). CONCLUSION: The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older.

Contribution of DNA Double-strand Break Repair Gene XRCC3 Genotypes to Triple-negative Breast Cancer Risk.

AIM: The DNA-repair gene X-ray repair cross-complementing group 3 (XRCC3) is important in DNA double-strand break repair and plays a critical part in initiation of carcinogenesis. Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype with no existing gene-targeting drugs and little knowledge on its genetic etiology. This study aimed to investigate the contribution of the XRCC3 genotype to individual TNBC susceptibility. MATERIALS AND METHODS: A total of 2,464 Taiwan citizens consisting of 1,232 breast cancer cases and 1,232 controls were enrolled in this case-control study, and genotyping of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539 and rs28903081 were performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We also conducted risk-stratified sub-group analyses to determine the association between the genotype and age- and hormone-related characteristics of breast cancer sub-groups. RESULTS: There was no significant difference between breast cancer and control groups in the distributions of the genotypic or allelic frequencies as for the XRCC3 rs1799794 (p=0.5195 and 0.9545), rs45603942 (p=0.3478 and 0.1449), rs861530 (p=0.4567 and 0.5081), rs3212057 (p=1.0000 and 1.0000), rs1799796 (p=0.8487 and 0.7315) and rs28903081 (p=1.0000 and 1.0000), respectively. However, the XRCC3 rs861539 TT genotype was more prevalent in patients with breast cancer [odds ratio (OR)=2.99, 95% confidence interval (CI)=1.62-5.55; p=0.0002], and especially among those who were younger than 55 years (OR=2.61, 95% CI=1.82-3.73; p=0.0001), with first menarche earlier than 12.2 years (OR=2.47, 95% CI=1.74-3.52; p=0.0001), with menopause at 49.0 years old or later (OR=2.53, 95% CI=1.76-3.62; p=0.0001), or with TNBC (OR=2.05, 95% CI=1.46-4.28; p=4.63*10(-4)). CONCLUSION: XRCC3 rs861539 TT is a potential predictive marker for TNBC in Taiwanese women and investigations in other populations are warranted for further universal application in cancer detection and prediction.

Contribution of Interleukin-4 Genotypes to Lung Cancer Risk in Taiwan.

AIM: Lung cancer is the leading cause of cancer-related death worldwide. Interleukin-4 (IL-4) is a typical pleiotropic T helper 2 cytokine involved in immunology during carcinogenesis. The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genetic polymorphisms to the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contributions of the promoter IL-4 polymorphic genotypes to lung cancer risk were investigated in 358 lung cancer patients and 716 age- and gender-matched healthy controls. In addition, the interaction between IL-4 and individual smoking status was also evaluated. RESULTS: The percentages of CC, CT and TT for IL-4 C-589T genotypes were differentially represented as 69.0%, 26.5% and 4.5% in the lung-cancer patient group and 61.3%, 30.4% and 8.3% in the non-cancer control group, respectively (p=0.0156). The TT genotype carriers were of lower risk for lung cancer (odds ratio (OR)=0.48, 95% confidence interval (CI)=0.27-0.86, p=0.0106) than the CC genotype carriers. We also analyzed the allelic frequency distributions and the results showed that the T allele of IL-4 C-589T conducted a protective effect on lung cancer susceptibility (p=0.0022). On the contrary, there was no difference in the distribution of genotypic or allelic frequencies among patients and controls for the IL-4 promoter T-1099G and C-33T. CONCLUSION: The TT genotype of IL-4 C-589T compared to the CC wild-type genotype may have a protective effect on lung cancer risk in Taiwan and may serve as an early detection and prediction marker.

Tumor Necrosis Factor-α Genotypes Are Associated with Hepatocellular Carcinoma Risk in Taiwanese Males, Smokers and Alcohol Drinkers.

AIM: Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, has high prevalence and mortality rates in Taiwan. Tumor necrosis factor-α (TNFα), an important proinflammatory cytokine, is involved in multiple physiological and pathogenic phenomena that lead to the destruction and dysregulation of tissues. The present study aimed to evaluate the contribution of TNFA genotype, together with cigarette smoking and alcohol drinking lifestyle to the risk of HCC. MATERIALS AND METHODS: In this hospital-based case-control study, association of TNFA single-nucleotide polymorphisms -1031T/C, -863C/A, -857T/C, -308G/A and +489A/G, with HCC risk were examined in 298 patients with HCC and 889 age- and gender-matched healthy controls. RESULTS: The percentages of AA, AG and GG TNFA -308G/A were 6.4%, 18.1% and 75.5% in the HCC patient group and 2.0%, 16.0% and 82.0% in the non-cancer control group, respectively. The AA and AG genotypes were associated with 3.42- and 1.23-fold higher odds of HCC than the GG genotype (95% confidence interval=1.76-6.63 and 0.87-1.74, respectively). No such significant difference was found for other polymorphic sites. We further stratified the populations by gender, cigarette smoking and alcohol drinking status to investigate their combined contributions with TNFA -308G/A genotype to HCC risk. The results showed that the AA and AG genotypes of TNFA -308G/A increased HCC susceptibility which was obvious among males, smokers, and alcohol drinkers, but not females, non-smokers, or non-drinkers (p=0.0003, 0.0003, 0.0014, 0.6127, 0.7442 and 0.3010, respectively). CONCLUSION: Our results suggest that the AA and AG polymorphism of TNFA -308G/A genotypes associated with HCC risk in Taiwan, particularly among males, smokers and alcohol drinkers.

Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotype to Gastric Cancer Risk in Taiwan.

AIM: It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. MATERIALS AND METHODS: In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. RESULTS: We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR)=1.64, 95% confidence interval (CI)=1.20-2.25, p=0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI=1.14-2.95, p=0.0159) and 1.87-fold (95% CI=1.04-3.34, p=0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR=11.27, 95% CI=3.72-34.17, p=0.0001), cigarette smoking (OR=23.20, 95% CI=6.24-86.23, p=0.0001) and Helicobacter pylori infection (OR=5.38, 95% CI=2.76-10.52, p=0.0001) on gastric cancer susceptibility. CONCLUSION: Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer.

Protective Effects of Pyridoxamine Against UVC-induced Programmed Cell Death in HaCaT Cells.

BACKGROUND: Exposure to ultraviolet (UV) light is closely related to human diseases, such as skin cancer, due to irreversible injuries to the skin cells. The UV-induced DNA damage and programmed cell death are important determinants for skin carcinogenesis. The aim of the present study was to investigate the anti-ultraviolet-C (UVC) effects of pyridoxamine in human keratinocyte HaCaT cells and its mechanisms of action. RESULTS: UVC-induced programmed cell death in HaCaT cells was abrogated by treated the cells immediately after UVC irradiation with 40, 80 and 160 µM of pyridoxamine. Monitoring the UVC-induced-specific reactive oxygen species, we found that 20, 40, 80 and 160 µM of pyridoxamine was also effective in suppressing the induction of reactive oxygen species by UVC. CONCLUSION: Overall, our results provided evidence showing that pyridoxamine was effective in protecting HaCaT cells from UVC-induced programmed cell death and may be a potential anti-UVC agent in life and clinical practice.

The association of methylenetetrahydrofolate reductase genotypes with the risk of childhood leukemia in Taiwan.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the MTHFR genotypic contribution to childhood ALL risk among different populations. METHODOLOGY/PRINCIPAL FINDINGS: In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The MTHFR C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of MTHFR C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42-0.87 and 0.24-0.97, respectively). As for gender, the boys carrying the MTHFR C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32-0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the MTHFR C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26-0.71, P=0.0016). CONCLUSIONS: Our results indicated that the MTHFR C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease.

The role of functional polymorphisms of cyclooxygenase 2 in renal cell carcinoma.

Renal cell carcinoma (RCC) accounts for about 3% of all cancer-related mortalities worldwide and the risk factors for the development of RCC have not yet been fully elucidated. Mounting evidence shows that overexpression of cyclo-oxygenase 2 (COX2) is commonly found in malignant tumors, including RCC. However, the contribution of genotypic variations of COX2 to RCC has not been studied. We hypothesized that variants of the COX2 gene are associated with risk of susceptibility to RCC in Taiwan. In this hospital-based case-control study, 92 patients with RCC and 580 age- and gender-matched cancer-free controls were recruited and the associations of COX2 A-1195G, G-765C, T+8473C, intron 1, intron 5, and intron 6 polymorphisms with RCC risk were examined in this Taiwanese population. The results showed that compared to the wild-type GG genotype, the CG genotype for COX2 G-765C was significantly associated with a lower risk of RCC (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0082). For other polymorphic sites, no obvious associations were found. There was also an obvious association of COX2 G765C genotype with reduced RCC risk among those without family cancer history (p=0.0331). These evidence indicated that COX2 G-765C genotype involved in the etiology of RCC and may serve as a novel genetic marker for susceptibility of RCC.

Association of caveolin-1 genotypes with renal cell carcinoma risk in Taiwan.

The alteration of caveolin-1 (Cav-1) during carcinogenesis is of great interest and its over-expression in the tumor cell cytoplasm can predict a poor prognosis of renal cell carcinoma (RCC). However, whether the over-expression in RCC is associated with inherited polymorphism is not clear. In this hospital-based case-control study, the association of Cav-1 genotypes with RCC risk in a central Taiwanese population was investigated. Ninety-two patients with RCC and five hundred and eighty of age/gender-matched healthy controls were recruited and genotyped for six polymorphic sites at Cav-1, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992). The results showed that there were statistically different distributions of the genotypic (P = 0.0170 and 0.0011) and allelic (P = 0.0033 and 0.0352) frequencies for the Cav-1 G14713A and T29107A polymorphisms among RCC patients and control subjects, respectively. As for the haplotype analysis, subjects carrying "GG/AT or GG/AA" at Cav-1 G14713A/T29107A showed a 2.06-fold increased odds ratio of RCC compared to those with GG/TT, while those of any other combinations were of unaltered odds ratios. In conclusion, this is the first report providing evidence showing that Cav-1 genotype is associated with RCC. The results showed that the G allele of the Cav-1 G14713A and the A allele of the Cav-1 T29107A are risky genetic factors for RCC susceptibility and the combinative GG/AT or GG/AA haplotype at Cav-1 G14713A/T29107A can serve as one of the RCC predictors for Taiwanese.

Evaluation of the contribution of methylenetetrahydrofolate reductase genotypes to Taiwan breast cancer.

The aim of the present study was to evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and its interaction with early-onset breast cancer risk in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed and their joint effects with individual age- and estrogen-related factors on breast cancer risk were discussed. In total, 1,232 patients with breast cancer and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The MTHFR C677T genotype, but not the A1298C, was differently distributed between cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in patients with cancer. In addition, females carrying MTHFR C677T CT or TT genotypes had a higher odds ratio of 1.21 (95% confidence interval=1.03-1.42, p=1.85E-5) for breast cancer, especially before the age of 45.4 years (odds ratio=1.51 and 95% confidence interval=1.20-1.90). Our results indicate that MTHFR C677T T allele was associated with increased risk of breast cancer in Taiwan, especially in cases who were 45.4 old or younger and with earlier menarche age (<12.2 years).

Associations of cyclooxygenase 2 polymorphic genotypes with bladder cancer risk in Taiwan.

AIM: Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in southwestern Taiwan. However, the genetic contribution to its etiology is not well-understood. The aim of this study is to evaluate the association of cyclooxygenase 2 (Cox-2) polymorphic genotypes with Taiwan bladder cancer patients. MATERIALS AND METHODS: Six polymorphic variants of Cox-2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same amount of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. RESULTS: Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs20417) genotypes were positively associated with bladder cancer risk (p=0.0102). Individuals with the Cox-2 -765GC genotypes were associated with higher prostate cancer risk than those with -765GG. CONCLUSION: Our findings provide evidence that the C allele of Cox-2 promoter G-765C may be associated with the overexpression of COX-2 during bladder cancer development and may be a useful marker for the early detection of bladder cancer.