Biomedical subjects

L L Hsieh

Publications and source records attributed to L L Hsieh.

At least 19 recordsLinked to original sources

PubMed2002

Biological monitoring of environment exposure to safrole and the Taiwanese betel quid chewing.

A rapid and sensitive biological monitoring (BM) method for assessing exposure to the environmental carcinogen safrole has been developed. The method is an isocratic high-performance liquid chromatographic (HPLC) analysis of urinary dihydroxychavicol (DHAB) and eugenol, the urinary metabolites of safrole. Good linearity, precision, and accuracy were demonstrated. A recovery of 98.8 +/- 5.4% (SD, n = 3) was found for DHAB and 84.1 +/- 3.4% (n = 3) for eugenol. The quantitation limits of the method were 8 ng for DHAB and 10 ng for eugenol. The validity of the method was demonstrated by a linear dose-response relationship observed in rats given oral doses of safrole at 30, 75, and 150 mg/kg body weight. The method was also used to monitor the environmental exposure to the Taiwanese betel quid (TBQ) chewing, because TBQ used in Taiwan not only contains areca (betel) nut, slaked lime, and catechu but also Piper betle inflorescence or its leaves. Both of the latter have a high content of safrole. The feasibility of the method to monitor TBQ chewing was demonstrated by an analysis of 153 spot human urine samples. The results showed that the p value of the nonparametric group comparison was < 0.001 for DHAB and 0.832 for eugenol. The TBQ chewers also exhibited a significantly higher rate of urinary DHAB (but not eugenol) than the nonchewers with an odd ratio of 3.47 (95% CI, 1.61-7.51). However, when only the eugenol-positive subjects were taken into analysis, the ratio rose to 24.38 (95% CI, 3.00-197.90).

Administration, Oral↗

PubMed2002

Decreased white blood cell counts in semiconductor manufacturing workers in Taiwan.

OBJECTIVES: To assess the systematic health effects on the liver, kidney, and haematological function tests of workers in semiconductors in Taiwan. METHODS: 926 workers of a semiconductor plant in Taiwan in July 1995 were investigated. Complete blood tests including liver, kidney, and haematological functions were available from 227 workers. RESULTS: There was a significantly lower mean (SD) white blood cell (WBC) count in male workers of photolithography (5870 (1190)/mm(3), p=0.003) and implantation (6190 (1150)/mm(3), p=0.018) than that of male control workers (7350 (1660)/mm(3)). There was a significantly higher prevalence of leukopenia in male photolithography workers (6 of 20; 30%) than in male control workers (1 of 18; 5.6%), the crude odds ratio (OR) was 7.3 (95% confidence interval (95% CI) 1 to 55.6), and the multivariate adjusted OR was 8.1 (95% CI 0.83 to 78.3). The tests for serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transferase (RGT), and creatinine were not significant among male workers. Female workers in photolithography had abnormal SGPT and RGT of borderline significance, the multivariate adjusted ORs were 9.6 (95% CI 0.86 to 107) and 6.35 (95% CI 0.53 to 75.8), respectively. CONCLUSIONS: This study suggests that leukopenia is a potential health effect in male fabrication workers of the semiconductor industry. The tasks of the process, maintenance, and equipment engineers which consisted mostly of men put them at risk for intermittent short term peak exposure to glycol ethers, ionising radiation, arsenic, or other toxins. The findings of this medical surveillance are significant; however, a further investigation of the aetiological factors and the subsequent health effects is necessary.

Adult↗

PubMed2001

Humoral response to p53 in human colorectal tumors: a prospective study of 1,209 patients.

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.

Adult↗

PubMed2001

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women.

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed, although less than 10% of female lung cancer patients are smokers. Until now, the etiological factor remains unknown. We hypothesize that high-risk human papillomavirus (HPV) 16/18 may be associated with lung cancer development based on high prevalence of p53 negative immunostainings in female lung tumors compared with that of male lung tumors. In this study, 141 lung cancer patients and 60 noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH), respectively. The concordant detection of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of 141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18 infection of nonsmoking female lung cancer patients is much higher at 10.12 (95% confidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval, 0.84-4.76) of nonsmoking male lung cancer patients. This result strongly suggests that HPV infection is associated with lung cancer development of nonsmoking female lung cancer patients. The high prevalence of HPV 16/18 infection may explain to a certain extent why Taiwanese women nonsmokers had a higher lung cancer mortality rate.

Female↗

PubMed2001

Mutations of p53 gene in human colorectal cancer: distinct frameshifts among populations.

We analyzed 57 p53 gene mutations in 181 colorectal cancer patients in Taiwan and compiled data on 475 independent p53 mutations in 1,156 primary colorectal cancer patients worldwide between 1992 to 1998. Transitions at the CpG sites were observed in 31 (54%) and 232 cases (49%), respectively. Frameshift mutations occurring within exons were observed in 11 (20%) and 50 cases (10%), respectively. Among the various populations studied, colorectal cancer in Taiwan had the lowest p53 mutation rate (31%), highest frequency (20%) of frameshift mutations and the second lowest rate (13%) of transversion mutation. Based on their relation to the base runs, the 61 frameshift mutations could be grouped into 4 subclasses. After corrections were made for differences in the base number in a run, the relative mutational frequency at a base run was found to be 9- to 47-fold over that in the no-run residues. The p53 frameshift mutational spectrum found in the cases in Taiwan, with respect to hotspot sequence, was significantly different from those in the selected database (p = 0.008). These data support that the patterns of high frequency of transitions at CpG sites and low frequency of transversions in base substitutions in the p53 gene are similar regardless of patient origin. However, these data also illustrate that frameshift mutations in the p53 gene in colorectal cancer patients are sequence dependent and are distinct among populations.

Adult↗

PubMed2001

Gender difference in DNA adduct levels among nonsmoking lung cancer patients.

Lung cancer is the leading cause of cancer mortality in Taiwanese women. Cigarette smoking cannot explain the high lung cancer mortality in this population because less than 10% of women in Taiwan are smokers. Therefore, environmental factors other than smoking may play an important role in lung cancer development in female nonsmokers. The purpose of this study was to elucidate the role of environmental carcinogen exposure in lung cancer development in Taiwanese female nonsmokers, based on DNA adduct formation. We collected nontumorous lung tissues resected from 62 nonsmoking lung cancer patients and 20 noncancer controls to investigate whether differences in susceptibility to DNA adduct formation exist between men and women. (32)P-postlabeling and ELISA (enzyme-linked immunosorbent assay) with polyclonal antibody against BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene)-DNA adduct were used to evaluate DNA adduct levels in lung tissues of study subjects. Our data showed that the DNA adduct levels of lung cancer patients determined by both assays were significantly higher than those of noncancer controls (P = 0.0001 for (32)P-postlabeling; P = 0.01 for ELISA). Moreover, DNA adduct levels in females were markedly greater than those in males (P = 0.014 for (32)P-postlabeling; P = 0.001 for ELISA). The difference in DNA adduct levels could not be explained by genetic polymorphisms of cytochrome P-4501A1 (CYP1A1) or glutathione S-transferase (GSTM1), as determined by polymerase chain reaction and restriction fragment length polymorphism. These results demonstrate that lung cancer patients have a higher susceptibility to DNA damage than that of noncancer controls. In addition, differences in susceptibility to DNA damage derived from environmental carcinogen exposure were observed between male and female nonsmokers. In conclusion, high susceptibility to DNA damage in females may partially explain the high mortality rate of lung cancer in nonsmoking Taiwanese women.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2001

Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis.

We describe a hepatocellular carcinoma partially surrounded by focal nodular hyperplasia in a 65-year-old female patient. In order to clarify the relationship of the hepatocellular carcinoma and the adjacent focal nodular hyperplasia, clonal analysis was conducted. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome-linked androgen receptor gene (HUMARA). The allelic bands from the amplification of the focal nodular hyperplasia and of the hepatocellular carcinoma showed a significant reduction in the intensity of one of the two alleles as compared with two alleles of equal intensity in the buff coat after HhaI digestion, which indicated that these two parts were monoclonal. However, the inactivated allele in the focal nodular hyperplasia and that in the hepatocellular carcinoma were not identical. Therefore, the focal nodular hyperplasia and hepatocellular carcinoma probably derived from the clonal expansion of two different clones.

Aged↗

PubMed2001

Influence of CETP gene variation on plasma lipid levels and coronary heart disease: a survey in Taiwan.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and chylomicron in exchange for triglycerides. Two CETP genetic variation and four polymorphisms are investigated by polymerase chain reaction (PCR) and restriction enzyme digestion in a population of Taiwan. The results show that a very rare variation frequency is found for CETP intron 14 splice site G-->A change. The population shows a predominant 405Ile allele (61%), 442Asp (97.7%), intron 1Taq1B(+) G allele (52%), intron 8 Msp1(-) A allele (89%) and intron 9 EcoN1(-) T allele (59.2%) in the control group. Patients with coronary heart disease (CHD) have more CETP EcoN1(+/+) GG genotype (25.3%) than the controls (13.6%) (P=0.049). The intron 1 Taq1B(-) A allele is associated with a high HDL cholesterol and apoA1 level, the EcoN1(+) G allele with a low apoA1 level and the 442Gly with both high total cholesterol and LDL cholesterol levels. Paradoxically, the 442Gly is also present with a higher frequency (5.2%) in HDL cholesterol > or =65 mg/dl group than that in the general population (2.3%) (P=0.04).

Adult↗

PubMed2001

Intraductal papillary neoplasia of the liver associated with hepatolithiasis.

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

Adult↗

PubMed2001

Characteristics of mutations in the p53 gene in oral squamous cell carcinoma associated with betel quid chewing and cigarette smoking in Taiwanese.

p53 mutations are etiologically associated with the development of oral squamous cell carcinomas (OSCCs) or are associated with exposure to specific carcinogens. In this study, we used PCR-single strand conformation polymorphism and DNA sequencing to analyze the conserved regions of the p53 gene (exons 5-9) in OSCC tumor specimens from 187 patients with varied histories of betel quid, tobacco and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations at exons 5-9. The incidence of p53 mutations was not associated with age, sex, TNM stage, status of cigarette smoking or betel quid chewing. However, alcohol drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53 mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the incidence of p53 mutations was still statistically significant (RR = 2.24; 95% CI, 1.21-4.15) after adjustment for cigarette smoking and betel quid (BQ) chewing. G:C to A:T transitions were the predominant mutations observed and associated with BQ and tobacco use. Alcohol drinking could enhance these transitions. After adjustment for cigarette smoking and BQ chewing, alcohol drinking still showed an independent effect on G:C to A:T transitions (RR = 2.41; 95% CI, 1.01-5.74). These findings strongly suggest an important contributive role of tobacco carcinogens to p53 mutation in this series of Taiwanese OSCCs and alcohol might enhance these mutagenic effects. As safrole-DNA adducts have been detected in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients with a BQ chewing history, we cannot rule out the possibility that safrole or other carcinogens present in the BQ may cause a similar pattern of mutagenesis. Determination of the role of safrole and other carcinogens present in BQ on the pattern of p53 gene mutation in OSCC will require further study.

Adult↗

PubMed2001

Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer.

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-alpha (TNF-alpha), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-alpha in OSF pathogenesis.

Adult↗

PubMed2001

Further characterization of apolipoprotein B genetic variations in Taiwanese.

Apolipoprotein B (apoB, protein; APOB, gene) is the main protein component of low-density lipoprotein (LDL) and plays an important role in blood lipid metabolism. Previously, we have reported four APOB coding regions, 5' signal peptide, and 3' repeat sequence polymorphisms in our population. In this report, we further characterize other APOB genetic variations. The results illustrate that the mutation frequencies for Arg3500Gln (1/846 alleles), Arg4019Trp (2/786 alleles), -265 C/T promoter region (0/264 alleles), and intron 2 A/G (0/450 alleles) are very low. Our population showed a frequency of 68.9% for the B4311 Ser allele. The B4311 Asn allele was associated with a higher apoB level than the Ser group (p < 0.05) in normal controls. In the normal controls, a higher B4311 Asn/Asn genotype frequency was found in the group with total cholesterol (TC) > 200 mg/dL and apoB concentration > 85 mg/dL than in the group with a TC < 200 mg/dL and apoB < 85 mg/dL (p = 0.03 for TC comparison).

Analysis of Variance↗

PubMed2001

Association of aflatoxin B(1)-albumin adduct levels with hepatitis B surface antigen status among adolescents in Taiwan.

Chronic hepatitis B virus (HBV) infection and aflatoxin B(1) (AFB(1)) exposure interact synergetically to induce hepatocellular carcinoma. One suggested mechanism for this interaction is the enhanced activation of AFB(1) in chronically HBV-infected individuals. Whereas no associations between chronic HBV infection and AFB(1)-albumin adducts were observed in several studies in adults, hepatitis B surface antigen (HbsAg)-positive children were found to have elevated adducts in Gambia. To assess the association between chronic HBV infection and AFB(1)-albumin adduct level in Taiwan, 200 junior high school adolescents from 20 townships were assayed for HBsAg and AFB(1)-albumin adducts. The mean AFB(1)-albumin adduct level was higher in HBsAg-positive compared with HBsAg-negative subjects. The association between HBsAg status and AFB(1)-albumin adducts remained after multivariate adjustment. This finding additionally supports the synergetic interaction between HBV and AFB(1), but the mechanism remains to be elucidated.

Adolescent↗

PubMed2001

Metabolic gene polymorphism frequencies in control populations.

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT2, GSTP, and EPHX) in the human population were determined. Major and significant differences in these frequencies were observed between Caucasians (n = 12,525), Asians (n = 2,136), and Africans and African Americans (n = 996), and some, but much less, heterogeneity was observed within Caucasian populations from different countries. No differences in allele frequencies were seen by age, sex, or type of controls (hospital patients versus population controls). No examples of linkage disequilibrium between the different loci were detected based on comparison of observed and expected frequencies for combinations of specific alleles.

Black People↗

PubMed2000

Mutational analysis of the p27(kip1) gene in hepatocellular carcinoma.

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcinoma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27(Kip1) mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 (GTC-->GGC) which was found in two cases. The second polymorphism was identified at codon 55 (GCG-->GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisher's exact test, 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.

Adult↗

PubMed2000

Association between aminolevulinate dehydrogenase genotype and blood lead levels in Taiwan.

This study was designed to evaluate the association between the aminolevulinate dehydrogenase (ALAD) genotype and blood lead levels in a general population environmentally exposed to lead. This study population of 660 subjects was secondarily sampled from the 3000 random samples of Taiwanese general population to study the distribution of blood lead levels in the Taiwanese population. A simple assay based on the polymerase chain reaction-restriction fragment length polymorphism technique was used to determine the genotype of the ALAD gene. This study found that most of the Taiwanese population was ALAD 1-1 (95.4%). Only 4.6% (30 subjects) of population were found to be 1-2 or 2-2. It has been hypothesized that the ALAD2 allele is associated with increased absorption of lead. This study found that individuals with ALAD2 alleles had 20% higher blood lead levels than persons with ALAD1 alleles (7.83 +/- 5.95 vs 6.51 +/- 5.03 micrograms/dL). However, the difference was not statistically significant, even after adjustment for other risk factors of environmental exposure. The result supports the previous finding that individuals with ALAD2 allele had higher blood lead levels. The small sample size and large amount of variation in our study may account for the insignificant association.

Asian People↗

PubMed1999

Physical activity, water intake and risk of colorectal cancer in Taiwan: a hospital-based case-control study.

The age-adjusted mortality rates of colorectal cancer have been rising in Taiwan over the past 2 decades, and colorectal cancer is now the third leading cause of cancer mortality in the country. We conducted a hospital-based case-control study to clarify the nature of the association between physical activity, water intake and colorectal-cancer risk in Taiwan. A total of 163 subjects (aged 33-80 years) with histologically confirmed primary colorectal cancer and 163 hospital controls were enrolled during 1992. Dietary intake, physical activity and other lifestyle activities were assessed using a comprehensive food-frequency and lifestyle-activity questionnaire. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic-regression analysis. A strong inverse dose-response relation between increased water intake and rectal cancer was found among men after adjustment for other risk factors (p for trend = 0.0005). The OR for rectal cancer among men in the highest tertile of water intake was 0.08 (95% CI, 0.02-0.35) compared with that among men in the lowest tertile (OR = 1). Similar but not significant trends were seen among women (p = 0.29). The OR for colon cancer among men with active leisure-time physical activity was 0.19 (95% CI, 0.05-0.77) times that among sedentary men (p for trend = 0.03). However, physical activity was not associated with colon-cancer risk among women (p = 0.48). No differences in the amount of water intake were found related to level of physical activity. These findings add to the evidence that leisure-time activity may reduce colon-cancer risk, not only in high-risk but also in low-risk populations, and support the potential beneficial effect of increased water intake in reducing colorectal-cancer risk.

Adult↗

PubMed1999

XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency.

Hereditary genetic defects in DNA repair lead to increased risk of cancer. Polymorphisms in several DNA repair genes have been identified; however, the impact on repair phenotype has not been elucidated. We explored the relationship between polymorphisms in the DNA repair enzyme, XRCC1 (codons 194, 280, and 399), and genotoxic end points measured in two populations: (a) placental aflatoxin B1 DNA (AFB1-DNA) adducts in a group of Taiwanese maternity subjects (n = 120); and (b) somatic glycophorin A (GPA) variants in erythrocytes from a group of North Carolina smokers and nonsmokers (n = 59). AFB1-DNA adducts were measured by ELISA, and erythrocyte GPA variant frequency (NN and NO) was assessed in MN heterozygotes with a flow cytometric assay. XRCC1 genotypes were identified by PCR-RFLPs. The XRCC1 399Gln allele was significantly associated with higher levels of both AFB1-DNA adducts and GPA NN mutations. Individuals with the 399Gln allele were at risk for detectable adducts (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.03). GPA NN variant frequency was significantly higher in 399Gln homozygotes (19.6 x 10(-6)) than in Gln/Arg heterozygotes (11.4 x 10(-6); P < 0.05) or Arg/Arg homozygotes (10.1 x 10(-6); P = 0.01). No significant effects were observed for other XRCC1 polymorphisms. These results suggest that the Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in deficient DNA repair.

Aflatoxin B1↗