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L R Wilkens

Publications and source records attributed to L R Wilkens.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of physician- and self-collected genital specimens for detection of human papillomavirus in men.

There is currently no consensus regarding the most appropriate methods of sampling for the detection of genital human papillomavirus (HPV) in men. We employed a recently developed collection method involving abrasion and moistened swabbing of the genital skin surface for the detection of HPV in a cohort of 136 university-affiliated males in Hawaii. Genital specimens collected by physicians using this method were compared with self-collected specimens from the same individuals obtained 24 h later. Self-collected specimens yielded a greater proportion of sufficient specimens than physician-collected specimens. HPV detection was comparable in physician- and self-collected specimens; detection was highest in the penile shaft (51.2% and 51.5%, respectively, P = 0.96), followed by the scrotum (41.2% and 46.2%, P = 0.43), the glans/coronal sulcus (31.9% and 33.1%, P = 0.84), and the foreskin (33.3% and 28.6%, P = 0.74). Site-specific agreement in HPV detection between paired physician- and self-collected samples ranged from 67.2% (kappa = 0.34) for the penile shaft to 95.0% (kappa = 0.89) for the foreskin. There was a high degree of concordance in HPV genotypes in HPV-positive pairs. The most common type was HPV type 84, which comprised approximately 15% of the specimens. The emery paper-swab method offers an efficient sampling method for genital HPV DNA detection in men that could be used both within and outside of the clinical setting.

Adolescent↗
PubMed2001

Association of tocopherols with circulating autoantibody levels against an oxidized DNA nucleoside in humans.

Autoantibodies against oxidized DNA bases are found in vivo and have been used as an indicator of oxidative damage, yet little is known concerning their individual variation and relation to serum micronutrients. Human plasma anti-5-hydroxymethyl-2'-deoxyuridine (HMdU) autoantibody (aAb) levels were repeatedly determined in 41 women and 11 men, and found to have small within-individual variation over time, but large between-individual differences. A positive association in both women (r = .5762, p = .0001) and men (r = .415, p = .2) between plasma total tocopherols and antibody levels was observed. Autoantibody levels were lower in postmenopausal women (8.37 +/- 1.61 vs. 17.18 +/- 2.85 in premenopausal women, p < .01), independently of plasma tocopherol. However, aAb titers in postmenopausal women were still significantly associated with plasma tocopherol levels and adjustment for menopausal status in women yielded a highly significant correlation between HMdU aAb levels and total tocopherol (r = .7342, p = .0001). Plasma malondialdehyde equivalents (MDA), a measure of lipid peroxidation, were also higher in individuals with either high plasma alpha-tocopherol or high beta+gamma-tocopherol levels. The positive association of tocopherols with markers of oxidative damage may reflect a response to the generation of endogenous oxidants associated with enhanced immune function. The decrease in aAb level in postmenopausal women may similarly reflect decreased immune function associated with decreased estrogen levels.

Adult↗
PubMed2001

CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population.

OBJECTIVE: In this investigation, we explored the hypothesis that genetic polymorphisms in the cytochrome P4501A1 (T3801C) and glutathione S-transferase classes mu and theta (GSTM1 and GSTT1) gene deletions promote the development of cervical dysplasia by moderating the activation and detoxification of polycyclic hydrocarbons and other compounds that influence oxidative stress and DNA adduct formation. METHODS: A multiethnic, case-control study of 131 women with biopsy-confirmed cervical squamous intraepithelial lesions (SIL) and 180 controls with cytologically normal cervical (Pap) smears was conducted between 1992 and 1996 in Honolulu, Hawaii. We collected in-person interviews, a blood sample to extract genomic DNA, and an exfoliated cervical cell sample to determine the presence and type of human papillomavirus (HPV) using PCR dot-blot hybridization. Genotyping for the CYP1A1 MspI allelic variant and deletion of the GSTM1 and GSTT1 gene loci followed a PCR method. RESULTS: Women who were homozygous, but not heterozygous, for the CYP1A1 MspI variant allele were at significantly increased risk of cervical SIL (odds ratio (OR) = 3.4; 95% confidence interval (CI) = 1.1-10.7) compared to women who were homozygous for the wild-type allele. Subjects with the GSTM1 null genotype had a nonsignificant elevated risk of cervical SIL (OR = 1.6; 95% CI = 0.8-3.0) compared to women with the gene present. No difference in the risk of cervical disease was associated with the GSTT1 null genotype. The combination of the CYP1A1 homozygous variant and the GSTM1 null genotypes increased the odds ratio for cervical SIL to 5.1 (95% CI = 1.3-20.7). There was no evidence for an interaction between genotype and exposure to tobacco smoke, alcohol drinking, or HPV DNA positivity. CONCLUSIONS: These findings, although based on a small number of subjects, suggest that the CYP1A1 MspI polymorphism may be a susceptibility factor for early, premalignant changes in the cervical epithelium.

Adult↗
PubMed2001

Pain, photophobia, and retinal and optic nerve function after phacoemulsification with intracameral lidocaine.

OBJECTIVE: To evaluate differences in pain, photophobia, retinal and optic nerve function in test eyes given intracameral lidocaine compared with control eyes given intracameral saline after phacoemulsification under topical anesthesia. DESIGN: Prospective paired-eye intervention study with random treatment allocation. PARTICIPANTS: Thirty eyes of 15 patients underwent cataract surgery in both eyes under topical anesthesia. INTERVENTION: The first eye of each patient was randomly assigned to either 0.5 ml preservative-free 2% intracameral lidocaine or 0.5 ml of intracameral sterile saline. Within 5 months, the second eye automatically received intracameral saline if the first eye received intracameral lidocaine or vice versa. MAIN OUTCOME MEASURES: The duration of surgery was recorded. Immediately after surgery, each patient was asked to evaluate the degree of pain and photophobia experienced during surgery using a nominal scale. In addition, in five patients, electroretinography (ERG) and visual evoked response (VER) were performed within 1 week before surgery, immediately after surgery, and 1 day after surgery. Amplitudes and latencies were calculated. RESULTS: There was no difference in the duration of surgery comparing test eyes given intracameral lidocaine with control eyes given sterile saline (P = 0.81). There was no significant difference in the level of pain reported when comparing test eyes given intracameral lidocaine with control eyes (P = 1.00). None of the patients reported any significant difference in photophobia between their two eyes (P = 1.00). When comparing ERG measurements, test eyes given intracameral lidocaine did not show any significant decrease in ERG amplitudes or prolonged latencies compared with control eyes. When comparing VER measurements, test eyes given intracameral lidocaine did not show any increase in P1 latencies compared with control eyes (P = 0.31). When evaluating all postoperative ERG results 1 day after surgery, there was a suggestion of improved cone function. CONCLUSIONS: Although intracameral lidocaine does not depress retinal or optic nerve function, the addition of intracameral lidocaine to topical anesthesia during phacoemulsification does not significantly reduce intraoperative pain or photophobia.

Adult↗
PubMed2001

Case-control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism.

Steroid hormones, such as estrogens, appear to be associated with ovarian carcinogenesis, but the precise biological mechanisms are unclear. Polymorphisms in genes that regulate the concentration of estrogens and their metabolites may contribute directly to the individual variation in ovarian cancer risk through a mechanism involving oxidative stress or indirectly by influencing ovarian cancer susceptibility associated with ovulation and reproduction. We conducted a population-based, case-control study of primary ovarian cancer between 1993 and 1999 in Hawaii to test several genetic and related hypotheses. A personal interview and blood specimen were obtained in the subjects' homes. In a sample of 129 epithelial ovarian cancer cases and 144 controls, we compared the frequencies of several polymorphisms in genes that regulate steroid hormone metabolism and catecholestrogen formation. Multivariate unconditional logistic regression was used to model the association of each genetic polymorphism separately after adjusting for age, ethnicity, and other covariates. The high-activity Val432 allele of the CYP1B1 gene, which may be linked to oxidative stress through elevated 4-hydroxylated catecholestrogen formation, was associated with an increased risk of ovarian cancer. The Val/Leu genotype for CYP1B1 was associated with an odds ratio of 1.8 (95% confidence interval, 1.0-3.3) and the Val/Val genotype with an odds ratio of 3.8 (95% confidence interval, 1.2-11.4) compared with the Leu/Leu genotype (P = 0.005). Tobacco smokers with at least one CYP1A1 (MspI) m2 allele, one CYP1B1 Val allele, one COMT Met allele, or two CYP1A2 A alleles were at significantly increased risk of ovarian cancer compared to never-smokers with CYP1A1 (MspI) ml/ml, CYP1B1 Leu/Leu, COMT Val/Val, or CYP1A2 A/A genotypes, respectively. We found a positive statistical interaction (P = 0.03) between tobacco smoking and the CYP1A1 (MspI) polymorphism on the risk of ovarian cancer. None of the other gene-environment (pregnancy, oral contraceptive pill use) or gene-gene interactions were statistically significant. Although not significant, there was a suggestion that the effect of the CYP1B1 Val allele was reduced substantially in the presence of the high-activity COMT Met allele. These findings suggest that the CYP1B1-Val allele and perhaps other genetic polymorphisms in combination with environmental or hormonal exposures are susceptibility factors for ovarian cancer.

Adult↗
PubMed2001

Combined effects of well-done red meat, smoking, and rapid N-acetyltransferase 2 and CYP1A2 phenotypes in increasing colorectal cancer risk.

Heterocyclic amines (HAAs) are suspected carcinogens that are formed in meat when it is cooked at high temperature for long durations. These compounds require metabolic activation by CYP1A2 and N-acetyltransferase (NAT) 2 or NAT1 before they can bind to DNA. It has been hypothesized that well-done meat increases the risk of colorectal cancer (CRC), especially in individuals with the rapid phenotype for CYP1A2 and NAT2. This association may be particularly strong in smokers because smoking is known to induce CYP1A2. We conducted a population-based case-control study on Oahu, Hawaii to specifically test this hypothesis. An in-person interview assessed the diet and preference for well-done red meat of 349 patients with CRC and 467 population controls. A urine collection after caffeine challenge and a blood collection were used to assess phenotype for CYP1A2 and NAT2 and genotype for NAT2 and NAT1, respectively. No statistically significant main effect association with CRC was found for red meat intake, preference for well-done red meat, the NAT2 rapid genotype, the CYP1A2 rapid phenotype or the NAT1*10 allele. However, in ever-smokers, preference for well-done red meat was associated with an 8.8-fold increased risk of CRC (95% confidence interval, 1.7-44.9) among subjects with the NAT2 and CYP1A2 rapid phenotypes, compared with smokers with low NAT2 and CYP1A2 activities who preferred their red meat rare or medium. No similar association was found in never-smokers, and there was no increased risk for well-done meat among smokers with a rapid phenotype for only one of these enzymes or for smokers with both rapid phenotypes who did not prefer their red meat well-done. These data provide additional support to the hypothesis that exposure to carcinogens (presumably HAAs) through consumption of well-done meat increases the risk of CRC, particularly in individuals who are genetically susceptible (as determined by a rapid phenotype for both NAT2 and CYP1A2) and suggest that smoking, by inducing CYP1A2, facilitates this effect.

Aged↗
PubMed2001

Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia.

Epidemiological studies have been inconsistent regarding a role for folate in the etiology of cervical dysplasia. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, which is involved in the methylation of homocysteine to methionine. A common variant of this enzyme, resulting from a 677C-->T (Ala-->Val) substitution in the gene, has been shown to have reduced activity and is associated with mild hyperhomocysteinemia. A multiethnic case-control study was used to examine the association of dietary folate and MTHFR genotype with the odds ratios (ORs) for cervical dysplasia among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. We collected blood samples for DNA extraction, cervical smears for cytological diagnosis, exfoliated cervical cells for human papillomavirus (HPV) DNA testing, and personal interviews from 150 women with squamous intraepithelial lesions (SILs) and from 179 women with cytologically normal (Pap) smears. We found a positive, monotonic trend (P = 0.02) in the ORs for cervical SILs associated with the number of variant MTHFR T alleles, after multivariate adjustment. Women with the heterozygous CT genotype had twice the risk of cervical SILs [OR, 2.0; 95% confidence interval (CI), 1.1-3.7], and women with the homozygous TT genotype had almost three times the risk of SILs (OR, 2.9; 95% CI, 1.0-8.8) compared to women with the homozygous MTHFR CC genotype. The dietary intakes of folate, vitamin B(6), and vitamin B(12) were inversely related to the ORs for cervical SILs, after adjustment for HPV DNA and other confounders. The OR among women in the highest quartile compared with women in the lowest quartile of folate intake was 0.3 (95% CI, 0.1-0.7; P for trend = 0.002). Women with the variant T allele and folate intakes below the median were at significantly elevated risk of cervical SILs (OR, 5.0; 95% CI, 2.0-12.2) compared to women with CC alleles and folate intakes above the median. HPV infection was a strong risk factor for cervical dysplasia, particularly among women with the variant T allele (OR, 46.6; 95% CI, 15.9-136.2). All associations of MTHFR genotype with the ORs for cervical SILs were independent of other risk factors under study. These findings suggest that the MTHFR T allele and reduced dietary folate may increase the risk for cervical SILs.

Adult↗
PubMed2000

Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as markers of cervical dysplasia.

BACKGROUND: An association between B-complex vitamins and related compounds with the development of cervical neoplasia is biologically plausible, yet to the authors' knowledge epidemiologic investigations of these potential biomarkers are limited. METHODS: A case-control study was designed to examine the relation between plasma folate, homocysteine, vitamin B(12), and cysteine and early, premalignant changes in cervical epithelial cells among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated cervical cells for human papillomavirus DNA testing by polymerase chain reaction, and a personal interview were obtained from 185 women with atypical squamous cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous intraepithelial lesions (SIL), and 191 women with cytologically normal (Papanicolaou) smears. RESULTS: Age-adjusted and ethnicity-adjusted mean plasma concentrations of cysteine, but not other nutrients, were significantly lower among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive trend in the odds ratio for SIL but not ASCUS was found for increased plasma homocysteine concentrations, but this finding was not statistically significant. High plasma levels of cysteine were associated with a reduced risk of ASCUS (P value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2-0.7) for the highest compared with the lowest quartile of cysteine concentration. A weak, negative relation between cysteine and the development of low grade SIL (LSIL) but not high grade SIL (HSIL) also was found. CONCLUSIONS: The results of the current study do not support the hypothesis that folate, homocysteine, or B(12) are markers of cervical dysplasia risk. A possible inverse association between plasma cysteine concentrations and the risk of cervical dysplasia needs further study.

Adult↗
PubMed2000

A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics.

The authors describe the design and implementation of a large multiethnic cohort established to study diet and cancer in the United States. They detail the source of the subjects, sample size, questionnaire development, pilot work, and approaches to future analyses. The cohort consists of 215,251 adult men and women (age 45-75 years at baseline) living in Hawaii and in California (primarily Los Angeles County) with the following ethnic distribution: African-American (16.3%), Latino (22.0%), Japanese-American (26.4%), Native Hawaiian (6.5%), White (22.9%), and other ancestry (5.8%). From 1993 to 1996, participants entered the cohort by completing a 26-page, self-administered mail questionnaire that elicited a quantitative food frequency history, along with demographic and other information. Response rates ranged from 20% in Latinos to 49% in Japanese-Americans. As expected, both within and among ethnic groups, the questionnaire data show substantial variations in dietary intakes (nutrients as well as foods) and in the distributions of non-dietary risk factors (including smoking, alcohol consumption, obesity, and physical activity). When compared with corresponding ethnic-specific cancer incidence rates, the findings provide tentative support for several current dietary hypotheses. As sufficient numbers of cancer cases are identified through surveillance of the cohort, dietary and other hypotheses will be tested in prospective analyses.

Black or African American↗
PubMed2000

Calibration of the dietary questionnaire for a multiethnic cohort in Hawaii and Los Angeles.

The performance of the dietary questionnaire used in a multiethnic cohort study in Hawaii and Los Angeles was assessed in a calibration substudy that compared diet reported from the questionnaire with three 24-hour dietary recalls. For the calibration substudy, subjects from each of eight subgroups defined by sex and ethnic group (African-American, Japanese-American, Latino, and White) were chosen randomly from among the cohort members, and each participant's previous day's diet was assessed by telephone recall on three occasions over approximately 2 months. After completing the three 24-hour recalls, each calibration subject was sent a second questionnaire; 1,606 persons completed three recalls and a second questionnaire (127 to 267 per ethnic-sex group). This report describes correlation coefficients and calibration slopes for the relation between the 24-hour recalls and second questionnaire values for a selected set of macro- and micronutrients, as absolute intakes, nutrient densities, and calorie-adjusted nutrients. In all subgroups, estimates of the correlation between the questionnaire and 24-hour recalls were greater after energy adjustment (average correlations ranged from 0.57-0.74 for nutrient densities and from 0.55-0.74 for calorie-adjusted nutrients) than when absolute nutrient values were used (average range 0.26-0.57). For absolute nutrient intakes, the correlations were greatest for Whites, somewhat lower for Japanese-Americans and Latinos, and lowest for African-Americans. After energy adjustment, the difference between subgroups were diminished, and the correlations were generally highly satisfactory.

Black or African American↗
PubMed2000

Intake of flavonoids and lung cancer.

BACKGROUND: To investigate the possible relationship between intake of flavonoids-powerful dietary antioxidants that may also inhibit P450 enzymes-and lung cancer risk, we conducted a population-based, case-control study in Hawaii. METHODS: An in-person interview assessed smoking history and usual intake of 242 food items for 582 patients with incident lung cancer and 582 age-, sex-, and ethnicity-matched control subjects. Subjects who donated a blood sample were genotyped for the P450 enzyme variant allele CYP1A1*2 by use of a polymerase chain reaction-based method. Logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). All P values are two-sided. RESULTS: After adjusting for smoking and intakes of saturated fat and beta-carotene, we found statistically significant inverse associations between lung cancer risk and the main food sources of the flavonoids quercetin (onions and apples) and naringin (white grapefruit). The lung cancer OR for the highest compared with the lowest quartile of intake was 0.5 (95% CI = 0.3-0.9) for onions (P for trend =.001) and 0.6 (95% CI = 0.4-1.0) for apples (P for trend =.03). The OR for the highest compared with the lowest tertile of intake for white grapefruit was 0.5 (95% CI = 0.2-0.9) (P for trend =.02). No association was found for important food sources of other flavonoids. Using published food-composition data for flavonoids, we found an inverse association between intake of quercetin and risk of lung cancer (P for trend =.07) that appears consistent with associations for its food sources. The effect of onions was particularly strong against squamous cell carcinoma (a cell type specifically associated with CYP1A1*2 in our study) and was modified by the CYP1A1 genotype, suggesting that CYP1A1 may play a role in this association. CONCLUSION: If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.

Aged↗
PubMed2000

Association of the myeloperoxidase -463G-->a polymorphism with lung cancer risk.

Myeloperoxidase, which is released from neutrophils in response to various pulmonary insults including tobacco smoke, is suspected to play a carcinogenic role in the lung. A G-to-A substitution polymorphism in the promoter region of the MPO gene has been suggested in in vitro studies to decrease gene transcription. We tested the association of this polymorphism with lung cancer in a population-based case-control study of 323 cases and 437 controls of Caucasian, Japanese, or Native Hawaiian ancestry in Hawaii. We found a marked difference in the frequency of the variant A allele among Caucasians (26%), Japanese (17%), and Hawaiians (13%). Overall, the variant allele was somewhat less frequent in cases than controls (P = 0.13). Individuals with the A/A genotype were found to be at a 50% decreased risk compared to those with two G alleles (95% confidence interval, 0.2-1.3). Although not statistically significant, this inverse association was suggested in both sexes and two of the three ethnic groups studied. Heterozygotes were at no decreased risk. Further work needs to clarify the functional relevance of the A allele in vivo and to confirm the inverse association of the A/A genotype with lung cancer in large epidemiological studies.

Adolescent↗
PubMed2000

Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study.

The evidence for a protective effect of vegetables, fruits, and legumes against prostate cancer is weak and inconsistent. We examined the relationship of these food groups and their constituent foods to prostate cancer risk in a multicenter case-control study of African-American, white, Japanese, and Chinese men. Cases (n = 1619) with histologically confirmed prostate cancer were identified through the population-based tumor registries of Hawaii, San Francisco, and Los Angeles in the United States and British Columbia and Ontario in Canada. Controls (n = 1618) were frequency-matched to cases on ethnicity, age, and region of residence of the case, in a ratio of approximately 1:1. Dietary and other information was collected by in-person home interview; a blood sample was obtained from control subjects for prostate-specific antigen determination. Odds ratios (OR) were estimated using logistic regression, adjusting for age, geographic location, education, calories, and when indicated, ethnicity. Intake of legumes (whether total legumes, soyfoods specifically, or other legumes) was inversely related to prostate cancer (OR for highest relative to lowest quintile for total legumes = 0.62; P for trend = 0.0002); results were similar when restricted to prostate-specific antigen-normal controls or to advanced cases. Intakes of yellow-orange and cruciferous vegetables were also inversely related to prostate cancer, especially for advanced cases, among whom the highest quintile OR for yellow-orange vegetables = 0.67 (P for trend = 0.01) and the highest quintile OR for cruciferous vegetables = 0.61 (P for trend = 0.006). Intake of tomatoes and of fruits was not related to risk. Findings were generally consistent across ethnic groups. These results suggest that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer.

Aged↗
PubMed2000

CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals.

The CYP1A1 and glutathione S-transferase enzymes (e.g., GSTM1 and GSTP1) are involved in the activation and conjugation of polycyclic aromatic hydrocarbons (PAHs), respectively, and are controlled by genes that are polymorphic. The CYP1A1*2 allelic variant has been associated with elevated urinary 1-hydroxypyrene (1-OHP), a proposed marker for internal dose of activated PAHs, in coke-oven workers. We investigated whether this association could be observed at low exposure levels, such as those experienced by the general population. We conducted a cross-sectional study among 188 individuals (106 Japanese, 60 Caucasians, and 22 Hawaiians) who were selected as controls in a population-based case-control study and provided lifestyle information, a 12-h urine specimen, and a blood sample. 1-OHP was analyzed by high-performance liquid chromatography after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping. Smokers excreted twice as much 1-OHP (geometric mean, 0.51 nmol/12 h) as nonsmokers (geometric mean, 0.27 nmol/12 h; P = 0.006). Overall and among nonsmokers, 1-OHP urinary levels did not differ by CYP1A1, GSTM1, or GSTP1 genotypes. However, after adjusting for age, ethnicity, and number of cigarettes per day, smokers with at least one CYP1A1*2 variant allele excreted 2.0-fold more 1-OHP than smokers with the wild-type genotype (P = 0.02). Similar results were obtained for the CYP1A1*3 variant allele. The present data add to the growing evidence suggesting that individuals with the (linked) CYP1A1*2 or *3 variant alleles have a greater capacity to activate PAHs from tobacco smoke and occupational exposure and, as a result, are at greater risk for PAH-related cancers, especially certain respiratory cancers.

Aged↗
PubMed2000

Relationships of TP53 codon 72 and HRAS1 polymorphisms with lung cancer risk in an ethnically diverse population.

Tobacco smoking is a strong cause of lung cancer. However, because only a small proportion of smokers develop the disease, other factors, including genetic susceptibility, may be important in determining lung cancer risk. Polymorphisms in the TP53 tumor suppressor gene and HRAS1 proto-oncogene have been associated in some studies with this cancer; we sought to replicate these associations in an ethnically diverse population in Hawaii. We conducted a population-based case-control study among 334 incident lung cancer cases and 446 controls of Caucasian, Japanese, or Native Hawaiian origin. In-person interviews collected detailed information on lifestyle risk factors. DNA was extracted from peripheral blood leukocytes, and genotyping was performed using a PCR-based assay for the TP53 codon 72 polymorphism and Southern blot analysis and PCR for allelic polymorphisms in the HRAS1 minisatellite. Logistic regression analyses were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for smoking and other risk factors. The presence of two rare HRAS1 alleles was associated with a 2.2-fold (95% CI, 1.0-5.0) increased lung cancer risk for all ethnic groups combined. The association was present in Native Hawaiians (OR, 5.2; 95% CI, 1.1-24.4) and was suggested for Japanese (OR, 2.8; 95% CI, 0.6-12.5); no association was observed in Caucasians (OR, 0.8; 95% CI, 0.2-3.6). This association was also observed for each lung cancer cell type. The presence of only one rare allele did not increase risk for any ethnic group or cell type. No significant association was found between the TP53 codon 72 polymorphism and lung cancer [OR, 1.4 (95% CI, 0.8-2.4) for the Pro/Pro genotype compared with the Arg/Arg genotype]. This study suggests that the presence of two rare HRAS1 alleles confers an increased lung cancer risk in Native Hawaiians and Japanese but possibly not in Caucasians. The amino acid replacement of arginine by proline at codon 72 of TP53 appears not to be important in determining lung cancer risk in this population.

Adult↗
PubMed1999

Association of the NAD(P)H:quinone oxidoreductase 609C-->T polymorphism with a decreased lung cancer risk.

The NAD(P)H:quinone oxidoreductase gene, NQO1, often carries a C-->T transition at bp 609, which has been associated with a reduced enzymatic activity and which may result in altered metabolic activation of tobacco smoke procarcinogens. We tested the association of this polymorphism with lung cancer risk in a population-based case-control study of 327 cases and 440 controls of Caucasian, Japanese, or Native Hawaiian ancestry in Hawaii. We found a notable difference in the frequency of the variant allele among Japanese (38%), Caucasians (20%), and Hawaiians (22%). Overall, the variant allele was less frequent in cases than in controls (P = 0.03). A significant inverse association was found in Japanese, with adjusted odds ratios of 0.8 (95% confidence interval, 0.4-1.5) and 0.3 (0.1-0.7) for the heterozygous and homozygous variant genotypes, respectively, compared with the homozygous wild-type genotype (P for genetic trend, 0.02). The association did not reach statistical significance in Caucasians and Hawaiians but was in the same direction.

Alleles↗