985 results on '"L. Le Marchand"'
Search Results
2. The Survival Impact of Second Primary Lung Cancer in Patients with Lung Cancer
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E. Choi, S. Luo, J. Aredo, L. Wilkens, A. Leung, L. Le Marchand, I. Cheng, H. Wakelee, and S. Han
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- 2021
3. Corrigendum to ‘Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer’
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J.M. Genkinger, K. Wu, M. Wang, D. Albanes, A. Black, P.A. van den Brandt, K.A. Burke, M.B. Cook, S.M. Gapstur, G.G. Giles, E. Giovannucci, G.G. Goodman, P.J. Goodman, N. Håkansson, T.J. Key, S. Männistö, L. Le Marchand, L.M. Liao, R.J. MacInnis, M.L. Neuhouser, E.A. Platz, N. Sawada, J.M. Schenk, V.L. Stevens, R.C. Travis, S. Tsugane, K. Visvanathan, L.R. Wilkens, A. Wolk, and S.A. Smith-Warner
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Oncology ,Hematology - Published
- 2021
4. Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a United States Prospective Cohort Consortium
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J Butt, WJ Blot, K Visvanathan, L Le Marchand, Y Chen, HD Sesso, S Wassertheil-Smoller, GYF Ho, LE Tinker, JD Potter, M Song, S Berndt, T Waterboer, M Pawlita, and M Epplein
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Oncology ,Epidemiology - Abstract
Auto-antibodies to tumor suppressor p53 are found in a subset of colorectal cancer (CRC) patients. A prospective cohort study in the US (Cancer Prevention Study II) has recently reported a statistically significant 1.8-fold increased odds for the development of CRC based on pre-diagnostic sero-positivity for p53; the magnitude of this association decreased with longer time-span between blood sampling and diagnosis. In the present study, we sought to examine this association in a large US CRC cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early CRC detection biomarker. Methods: Antibody responses to p53 were measured in pre-diagnostic blood samples of 3,702 incident CRC cases (median [range] follow-up: 7.3 years [0–40 years]) and an equal number of controls, matched by age, race, and sex, from 9 US prospective cohorts. The association of sero-positivity to p53 with CRC risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Results: Overall, 5% of controls and 7% of cases were sero-positive to p53, resulting in a statistically significant 33% increased CRC risk (OR: 1.33; 95% CI: 1.09, 1.61). The association was strongest for CRC diagnoses within 2 years after blood draw (OR: 2.73; 95% CI: 1.67, 4.45), with 15% sero-positive cases compared to 6% sero-positive controls. The number of sero-positive cases decreased with longer follow-up time (2–
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- 2020
5. Ethnic Groups
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L. N. Kolonel and L. Le Marchand
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- 2014
6. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes
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D J, Hunter, E, Riboli, C A, Haiman, D, Albanes, D, Altshuler, S J, Chanock, R B, Haynes, B E, Henderson, R, Kaaks, D O, Stram, G, Thomas, M J, Thun, H, Blanché, J E, Buring, N P, Burtt, E E, Calle, H, Cann, F, Canzian, Y C, Chen, G A, Colditz, D G, Cox, A M, Dunning, H S, Feigelson, M L, Freedman, J M, Gaziano, E, Giovannucci, S E, Hankinson, J N, Hirschhorn, R N, Hoover, T, Key, L N, Kolonel, P, Kraft, L, Le Marchand, S, Liu, J, Ma, S, Melnick, P, Pharaoh, M C, Pike, C, Rodriguez, V W, Setiawan, M J, Stampfer, E, Trapido, R, Travis, J, Virtamo, S, Wacholder, and W C, Willett
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Cohort Studies ,Male ,Humans ,Prostatic Neoplasms ,Breast Neoplasms ,Female ,Penetrance ,Gonadal Steroid Hormones ,Genes, Neoplasm - Abstract
Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.
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- 2005
7. Meat intake, metabolic genes and colorectal cancer
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L, Le Marchand
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Meat ,Polymorphism, Genetic ,Arylamine N-Acetyltransferase ,Smoking ,Cytochrome P-450 CYP2E1 ,Meat Products ,Cytochrome P-450 CYP1A2 ,Heterocyclic Compounds ,Risk Factors ,Animals ,Humans ,Cattle ,Polycyclic Compounds ,Amines ,Colorectal Neoplasms - Published
- 2002
8. Adjustment for smoking in lung cancer analyses in the EPIC cohort
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H C, Boshuizen, H B, Bueno-de-Mesquita, H P, Altenburg, A, Agudo, L, Le Marchand, F, Berrino, L, Janzon, T, Rasmuson, P, Vineis, A, Lukanova, J, Linseisen, E, Riboli, and A, Miller
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Male ,Lung Neoplasms ,Time Factors ,Smoking ,Diet Surveys ,Cohort Studies ,Europe ,Risk Factors ,Humans ,Female ,Smoking Cessation ,Prospective Studies ,Follow-Up Studies ,Proportional Hazards Models - Published
- 2002
9. Using multiple imputation methods to estimate relative risks in small EPIC lung cancer subsets
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H P, Altenburg, A, Agudo, F, Berrino, H C, Boshuizen, H B, Bueno-de-Mesquita, L, Janzon, L, Le Marchand, J, Linseisen, A, Lukanova, T, Rasmuson, P, Vineis, E, Riboli, and A, Miller
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Male ,Risk ,Likelihood Functions ,Lung Neoplasms ,Statistics as Topic ,Markov Chains ,Cohort Studies ,Logistic Models ,Bias ,Data Interpretation, Statistical ,Humans ,Regression Analysis ,Female ,Monte Carlo Method - Published
- 2002
10. Etiologic research on lung cancer in Hawaii: the roles of smoking, phytochemicals and metabolic genes
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L, Le Marchand
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Lung Neoplasms ,Epidemiologic Research Design ,Smoking ,Humans ,Feeding Behavior ,Hawaii - Published
- 2002
11. RE: 'CONTROL FOR ENVIRONMENTAL RISK FACTORS IN ASSESSING GENETIC EFFECTS ON DISEASE FAMILIAL AGGREGATION'
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L P, Zhao, L, Le Marchand, R, Haile, and J, Grove
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Models, Statistical ,Models, Genetic ,Epidemiology ,business.industry ,Genetic Diseases, Inborn ,Family aggregation ,Environmental Exposure ,Disease ,Environmental risk ,Risk Factors ,Environmental health ,Humans ,Medicine ,business ,Control (linguistics) - Published
- 1993
12. Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia
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M T, Goodman, K, McDuffie, B, Hernandez, L R, Wilkens, C C, Bertram, J, Killeen, L, Le Marchand, J, Selhub, S, Murphy, and T A, Donlon
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Adult ,Vaginal Smears ,Oxidoreductases Acting on CH-NH Group Donors ,Polymorphism, Genetic ,Genotype ,Papillomavirus Infections ,Uterine Cervical Neoplasms ,Folic Acid Deficiency ,Diet ,Epidemiologic Studies ,Tumor Virus Infections ,Risk Factors ,Case-Control Studies ,DNA, Viral ,Ethnicity ,Odds Ratio ,Humans ,Female ,Papillomaviridae ,Precancerous Conditions ,Methylenetetrahydrofolate Reductase (NADPH2) ,Papanicolaou Test - Abstract
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.
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- 2001
13. Combined effects of well-done red meat, smoking, and rapid N-acetyltransferase 2 and CYP1A2 phenotypes in increasing colorectal cancer risk
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L, Le Marchand, J H, Hankin, L R, Wilkens, L M, Pierce, A, Franke, L N, Kolonel, A, Seifried, L J, Custer, W, Chang, A, Lum-Jones, and T, Donlon
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Male ,Meat ,Arylamine N-Acetyltransferase ,Smoking ,Environmental Exposure ,Middle Aged ,Carcinogens, Environmental ,Diet ,Phenotype ,Cytochrome P-450 CYP1A2 ,Risk Factors ,Enzyme Induction ,Humans ,Female ,Genetic Predisposition to Disease ,Cooking ,Colorectal Neoplasms ,Aged - Abstract
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.
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- 2001
14. Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash
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M, García-Closas, K M, Egan, J, Abruzzo, P A, Newcomb, L, Titus-Ernstoff, T, Franklin, P K, Bender, J C, Beck, L, Le Marchand, A, Lum, M, Alavanja, R B, Hayes, J, Rutter, K, Buetow, L A, Brinton, and N, Rothman
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Adult ,Epidemiologic Studies ,Mouth Mucosa ,Mouthwashes ,Humans ,Reproducibility of Results ,Breast Neoplasms ,Female ,DNA ,Middle Aged ,Polymerase Chain Reaction ,Aged ,Specimen Handling - Abstract
Blood samples are an excellent source of large amounts of genomic DNA. However, alternative sources are often needed in epidemiological studies because of difficulties in obtaining blood samples. This report evaluates the buccal cytobrush and alcohol-containing mouthwash protocols for collecting DNA by mail. Several DNA extraction techniques are also evaluated. The study was conducted in two phases. In phase 1, we compared cytobrush and mouthwash samples collected by mail in two different epidemiological studies: (a) cytobrush samples (n = 120) from a United States case-control study of breast cancer; and (b) mouthwash samples (n = 40) from a prospective cohort of male United States farmers. Findings from phase 1 were confirmed in phase 2, where we randomized cytobrush (n = 28) and mouthwash (n = 25) samples among participants in the breast cancer study to directly compare both collection methods. The median human DNA yield determined by hybridization with a human DNA probe from phenol-chloroform extracts was 1.0 and 1.6 microg/2 brushes for phases 1 and 2, respectively, and 27.5 and 16.6 microg/mouthwash sample for phases 1 and 2, respectively. Most (94-100%) mouthwash extracts contained high molecular weight DNA (23 kb), in contrast to 55-61% of the brush extracts. PCR success rates for amplification of beta-globin gene fragments (268, 536, and 989 bp) were similar for cytobrush and mouthwash phenol-chloroform extracts (range, 94.4-100%). Also, we obtained high success rates in determining the number of CAG repeats in the androgen receptor gene, characterizing tetranucleotide microsatellites in six gene loci, and screening for mutations in the BRCA1/2 genes in a subset of phenol-chloroform DNA extracts. Relative to DNA extracted by phenol-chloroform from cytobrush samples, DNA extracted by NaOH had lower molecular weight, decreased PCR success rates for most assays performed, and unreliably high spectrophotometer readings for DNA yields. In conclusion, although DNA isolated from either mouthwash or cytobrush samples collected by mail from adults is adequate for a wide range of PCR-based assays, a single mouthwash sample provides substantially larger amounts and higher molecular weight DNA than two cytobrush samples.
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- 2001
15. Feasibility of collecting buccal cell DNA by mail in a cohort study
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L, Le Marchand, A, Lum-Jones, B, Saltzman, V, Visaya, A M, Nomura, and L N, Kolonel
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Aged, 80 and over ,Male ,Polymorphism, Genetic ,Mouth Mucosa ,Mouthwashes ,DNA ,Middle Aged ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Specimen Handling ,Cohort Studies ,Feasibility Studies ,Humans ,Female ,Aged - Abstract
This study assessed the feasibility of obtaining buccal cell DNA by mail from participants in a large, community-based cohort study in Hawaii. Mouthwash collection kits were sent to a total of 355 randomly selected Japanese, Caucasian, and Hawaiian cohort members. Subjects were requested to swish 10 ml of mouthwash in their mouth for 60 s and expel it into a collection cup, which they mailed back to our laboratory. Half of the subjects were requested to collect a second sample. After up to two mailings and two reminder phone calls, two-thirds of the subjects returned a sample. The participation rate was lower for Hawaiians (59.0%) than for Caucasians (68.1%) and Japanese (76.3%). Participation was not affected by requesting two specimens. Participants did not differ from the total sample in terms of education and smoking status. The mean DNA yield was lower in females (41.7 microg) than males (53.4 microg) and in Japanese (37.8 microg) as compared with Hawaiians (51.9 microg) and Caucasians (54.5 microg). For subjects who returned two samples, the DNA yields were similar when both specimens were extracted in the same batch. All samples were successfully genotyped for polymorphisms in the CYP1A1, CYP2E1, GSTM1, GSTT1, and NQO1 genes by PCR-RFLP. From these and previous data, we conclude that, in situations where blood samples cannot be obtained, mail collection of mouthwash samples should be considered because it yields substantial amounts of high-quality genomic DNA for large numbers of study subjects.
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- 2001
16. Case-control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism
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M T, Goodman, K, McDuffie, L N, Kolonel, K, Terada, T A, Donlon, L R, Wilkens, C, Guo, and L, Le Marchand
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Adult ,Genotype ,Comorbidity ,Risk Assessment ,Hawaii ,Cohort Studies ,Cytochrome P-450 Enzyme System ,Gene Frequency ,Reference Values ,Confidence Intervals ,Odds Ratio ,Humans ,Aged ,Ovarian Neoplasms ,Polymorphism, Genetic ,Incidence ,Carcinoma ,Smoking ,Estrogens ,Middle Aged ,Estrogens, Catechol ,Parity ,Logistic Models ,Case-Control Studies ,Cytochrome P-450 CYP1B1 ,Multivariate Analysis ,Female ,Aryl Hydrocarbon Hydroxylases - Abstract
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.
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- 2001
17. Relationships of TP53 codon 72 and HRAS1 polymorphisms with lung cancer risk in an ethnically diverse population
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L M, Pierce, L, Sivaraman, W, Chang, A, Lum, T, Donlon, A, Seifried, L R, Wilkens, A F, Lau, and L, Le Marchand
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Adult ,Male ,Lung Neoplasms ,Polymorphism, Genetic ,Middle Aged ,Genes, p53 ,Polymerase Chain Reaction ,Proto-Oncogene Mas ,White People ,Genes, ras ,Asian People ,Risk Factors ,Case-Control Studies ,Ethnicity ,Odds Ratio ,Humans ,Female ,Aged - Abstract
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.
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- 2000
18. CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals
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P V, Nerurkar, L, Okinaka, C, Aoki, A, Seifried, A, Lum-Jones, L R, Wilkens, and L, Le Marchand
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Male ,Lung Neoplasms ,Polymorphism, Genetic ,Smoking ,Middle Aged ,Isoenzymes ,Glutathione S-Transferase pi ,Risk Factors ,Case-Control Studies ,Occupational Exposure ,Cytochrome P-450 CYP1A1 ,Humans ,Female ,Genetic Predisposition to Disease ,Polycyclic Aromatic Hydrocarbons ,Life Style ,Biomarkers ,Chromatography, High Pressure Liquid ,Aged ,Glutathione Transferase - Abstract
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.
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- 2000
19. Association of the myeloperoxidase -463G--a polymorphism with lung cancer risk
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L, Le Marchand, A, Seifried, A, Lum, and L R, Wilkens
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Adult ,Male ,Lung Neoplasms ,Polymorphism, Genetic ,Adolescent ,Middle Aged ,Hawaii ,White People ,Amino Acid Substitution ,Japan ,Risk Factors ,Humans ,Female ,Promoter Regions, Genetic ,Aged ,Peroxidase - Abstract
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.
- Published
- 2000
20. Underreporting of family history of colon cancer: correlates and implications
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K, Glanz, J, Grove, L, Le Marchand, and C, Gotay
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Adult ,Aged, 80 and over ,Male ,Risk ,Health Knowledge, Attitudes, Practice ,Middle Aged ,Hawaii ,Bias ,Humans ,Female ,Genetic Testing ,Registries ,Colorectal Neoplasms ,Medical History Taking ,Aged - Abstract
Scientific advances in cancer genetics, risk counseling, and management of high-risk individuals require information about familial cancer history. Because some people may not report, or may be unaware of, cancer in their families, it is important to examine the extent of underreporting of family history. We mailed a survey to first-degree relatives of patients with histologically confirmed diagnoses of colorectal cancer (CRC) before age 60 (n = 426, 77% response rate). Analyses examined the extent of underreporting of family history and its predictors (demographics, cancer characteristics, knowledge, and communication) and correlates (cancer worry, perceived risk). Logistic regression analysis was performed using generalized estimating equations to account for family clusters. Despite confirmed diagnosis of CRC in a parent or sibling, 25.4% of respondents reported having no first-degree relative with colon cancer. In multivariate models, the most significant predictor of awareness of a relative's CRC was the stage-at-diagnosis; also, males and those with low knowledge about colon cancer were significantly less aware. Awareness of a relative's CRC was associated with higher cancer worry and risk perception, and being a college graduate contributed independently to increased risk perception. Sole dependence on mailed self-administered questionnaires may lead to substantial underreporting of familial colon cancers, especially those that are in situ or localized.
- Published
- 1999
21. Association of the NAD(P)H:quinone oxidoreductase 609C--T polymorphism with a decreased lung cancer risk
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H, Chen, A, Lum, A, Seifried, L R, Wilkens, and L, Le Marchand
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Male ,Lung Neoplasms ,Polymorphism, Genetic ,Genotype ,Genetic Variation ,Risk Assessment ,Hawaii ,White People ,Cytosine ,Asian People ,Japan ,Risk Factors ,Case-Control Studies ,NAD(P)H Dehydrogenase (Quinone) ,Odds Ratio ,Humans ,Point Mutation ,Female ,Registries ,Alleles ,Thymine - Abstract
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.
- Published
- 1999
22. Correlates of intentions to obtain genetic counseling and colorectal cancer gene testing among at-risk relatives from three ethnic groups
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K, Glanz, J, Grove, C, Lerman, C, Gotay, and L, Le Marchand
- Subjects
Adult ,Male ,Health Knowledge, Attitudes, Practice ,Motivation ,Asian ,Genetic Counseling ,Middle Aged ,Hawaii ,White People ,Logistic Models ,Japan ,Socioeconomic Factors ,Risk Factors ,Surveys and Questionnaires ,Educational Status ,Humans ,Family ,Female ,Genetic Testing ,Colorectal Neoplasms ,Attitude to Health - Abstract
An understanding of factors associated with interest in genetic counseling and intentions to obtain colorectal cancer susceptibility testing is an important foundation for developing education, counseling, and genetic services and policies.A survey was mailed to first-degree relatives of patients diagnosed with colorectal cancer. The respondents (n = 426, 77% response rate) are siblings and adult children of Caucasian, Japanese, and Hawaiian ethnicity. Data collection was guided by a conceptual framework and included questions on demographics, family cancer history, predisposing factors (cancer worry, perceived risk, well-being), and enabling factors (decision preferences, social support, and health care factors). Logistic regression analysis on two binary dependent variables (interest in counseling and intentions to get genetic testing) was performed using Generalized Estimating Equations to account for family clusters.Forty-five % of respondents were interested in genetic counseling, and 26% "definitely" intended to get genetic testing for colon cancer when available. For counseling interest, the most important predictors were education, Hawaiian ethnicity, cancer worry, and family support. Cancer worry, perceived risk, and age (older) were directly, and Japanese ethnicity was inversely, associated with testing intentions.High rates of interest in cancer genetic testing are similar to those found in other studies. Ethnic differences reveal a paradox between objective population risk (higher for Japanese) and greater concerns (among Hawaiians). The substantial lack of awareness of family history warrants further research. Culturally sensitive education and counseling are needed for managing the likely high demand for personalized information about hereditary cancer risk.
- Published
- 1999
23. Independent and joint effects of family history and lifestyle on colorectal cancer risk: implications for prevention
- Author
-
L, Le Marchand, L R, Wilkens, J H, Hankin, L N, Kolonel, and L C, Lyu
- Subjects
Male ,Meat ,Alcohol Drinking ,Hawaii ,White People ,Sex Factors ,Asian People ,Risk Factors ,Confidence Intervals ,Ethnicity ,Odds Ratio ,Animals ,Humans ,Genetic Predisposition to Disease ,Life Style ,Aged ,Rectal Neoplasms ,Incidence ,Age Factors ,Feeding Behavior ,Middle Aged ,Gene Expression Regulation, Neoplastic ,Logistic Models ,Case-Control Studies ,Colonic Neoplasms ,Cattle ,Female - Abstract
It has been suggested that, for a substantial proportion of "sporadic" colorectal cancers (CRCs), inheritance determines individual susceptibility and that lifestyle determines which susceptible individuals express cancer. Because the genetic basis of this inherited susceptibility remains undefined, we used family history of the disease as a proxy for a genetic predisposition to examine its interactions with a variety of lifestyle factors in a large population-based case-control study of CRC. The subjects were 698 male and 494 female Japanese, Caucasian, Filipino, Hawaiian, and Chinese patients diagnosed with CRC in Hawaii during 1987-1991 and 1192 population controls matched to cases on age, sex, and ethnicity. Fourteen percent of the cases and 6% of the controls reported a family history of CRC among parents or siblings. After adjusting for other covariates, significant interactions with family history were found for beef and ethanol intakes in males (P = 0.03). Relative to men without a family history and whose intake fell in the lower third, odds ratios (ORs) for CRC for men with a family history and in the upper tertile of intake were 10.8 [95% confidence interval (CI), 4.2-27.6] and 7.5 (CI, 3.1-18.2) for beef and ethanol, respectively. The corresponding ORs for men without a family history and in the upper tertile were 1.5 (CI, 1.0-2.3) and 1.4 (CI, 1.0-1.9), respectively. No interactions were detected in women. Using a summary measure of lifestyle, we found that family history was not associated with CRC among men who were at the lower-risk tertile for all of the lifestyle risk factors. In contrast, the OR for men with a family history and at the higher-risk tertile for all of the lifestyle variables was 11.7 (CI, 5.8-23.9). In the absence of a family history, this OR was 4.8 (CI, 3.2-7.2). These data suggest that family history increases the risk of sporadic CRC in men mainly through its interaction with lifestyle exposures, primarily a high beef and ethanol intake, and are consistent with recent reports of effect modifications of dietary associations by metabolic genes. Computation of population attributable risks also suggested that a comprehensive reduction in exposure to lifestyle risk factors--and more specifically to ethanol and beef for individuals with a familial predisposition for the disease--may have a large beneficial effect on CRC incidence.
- Published
- 1999
24. Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens
- Author
-
L, Le Marchand, L, Sivaraman, L, Pierce, A, Seifried, A, Lum, L R, Wilkens, and A F, Lau
- Subjects
Adult ,Lung Neoplasms ,Genotype ,Cytochrome P-450 CYP2E1 ,Middle Aged ,Isoenzymes ,Plants, Toxic ,Tobacco ,Carcinogens ,Cytochrome P-450 CYP1A1 ,Humans ,Genetic Predisposition to Disease ,Polycyclic Aromatic Hydrocarbons ,Alleles ,Aged ,Glutathione Transferase - Abstract
The dramatic shift in the pathological presentation of lung cancer [the proportional decrease in squamous cell carcinoma (SCC) and increase in adenocarcinoma (AC)] observed in the United States after the 1950s may have taken place as the result of the reduction in polycyclic aromatic hydrocarbons (PAHs) and the increase in N-nitrosamines in inhaled smoke from filtered low-yield cigarettes. The predominant mutation patterns of these tumors also suggest differences in their etiology. We tested the hypothesis that genetic susceptibility to PAHs, as determined by polymorphisms in CYP1A1 and GSTM1, predominantly causes lung SCCs, and susceptibility to nitrosamines, as determined by polymorphisms in CYP2E1, predominantly causes lung ACs. CYP1A1 and GSTM1 play a major role in the metabolic activation and detoxification of PAHs, respectively, and CYP2E1 plays a major role in the metabolic activation of nitrosamines. We conducted a population-based case-control study among 341 incident lung cancer cases and 456 controls of Caucasian, Japanese, or Hawaiian origin. In-person interviews collected detailed information on lifestyle risk factors, and DNA extracted from peripheral leukocytes was used in PCR-based genotyping assays. Logistic regression analyses were used to compute odds ratios and 95% confidence intervals (CIs) for each cell type, adjusting for smoking and dietary variables. The presence of at least one copy of the CYP1A1 MspI variant allele was found to be associated with a 2.4-fold (95% CI, 1.2-4.7) increase in the risk of SCC when this gene was considered singly and a 3.1-fold (95% CI, 1.2-7.9) increase in the risk of SCC when combined with a GSTM1 deletion. No significant association was found between MspI and all lung cancers or other cell types or with the CYP1A1 exon 7 polymorphism. In contrast, the CYP2E1 RsaI and DraI polymorphisms were not clearly related to SCC risk, but these homozygous variant genotypes were associated with a 10-fold (95% CI, 0.0-0.5) decrease in the risk of overall lung cancer (RsaI variant) and AC (DraI variant) compared to the homozygous wild-type genotypes. Inverse associations with these two closely linked CYP2E1 polymorphisms were also suggested for small cell carcinoma. In agreement with past experimental and epidemiological data, the associations found in this study between CYP1A1 and lung SCC and between CYP2E1 and lung AC suggest a certain specificity of tobacco smoke PAHs for lung SCC and tobacco-specific nitrosamines for lung ACs.
- Published
- 1998
25. A simple mouthwash method for obtaining genomic DNA in molecular epidemiological studies
- Author
-
A, Lum and L, Le Marchand
- Subjects
Adult ,Male ,Molecular Epidemiology ,Base Sequence ,Genome, Human ,Molecular Sequence Data ,Mouth Mucosa ,Mouthwashes ,Middle Aged ,DNA, Ribosomal ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Specimen Handling ,Genetic Techniques ,Feasibility Studies ,Humans ,Female ,Aged - Abstract
Genomic DNA for genetic analyses has traditionally been derived from blood samples. With the availability of PCR techniques requiring only minute amounts of DNA and the current demand for high-volume testing, a less invasive, simpler to perform, and cheaper method to obtain DNA is desirable. We developed a method to obtain high-quality genomic DNA from buccal cells that has high acceptability and allows for a large number of PCR assays from a single sample. Sixty subjects vigorously swished 10 ml of undiluted commercial mouthwash in the mouth for 60 s and expelled the liquid into a collection container. DNA was isolated from the buccal cells with a rapid method using proteinase K digestion, phenol-chloroform extraction, and ethanol precipitation. Electrophoretic analysis of the extracted DNA showed detectable levels of high molecular weight genomic DNA in all samples. The DNA yields ranged from 0.2 to 134.0 microg, for an average of 49.7 microg. Using these samples, all 60 subjects were successfully genotyped by PCR-based assays for polymorphisms in the CYP1A1 (MspI and exon 7), CYP2E1 (RsaI), GSTM1, GSTT1, and NQO1 genes, confirming that the quality of DNA isolated from mouthwash samples was sufficient to reliably support PCR amplification. Storage of the (unprocessed) specimens at room temperature or at 37 degrees C for 1 week (temperature conditions that may be encountered when mailing samples) or at -20 degrees C for at least 6 months did not affect the DNA yield or ability to PCR amplify the samples. The results suggest that this mouthwash procedure may be suitable for large community-based studies of genetic susceptibility to disease in which samples can be collected by the participants themselves, mailed back to the study center, and stored for months prior to DNA analysis.
- Published
- 1998
26. Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States
- Author
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D J, Galanis, L N, Kolonel, J, Lee, and L, Le Marchand
- Subjects
Adult ,Incidence ,Age Factors ,Breast Neoplasms ,Middle Aged ,Prognosis ,Body Height ,Hawaii ,Body Mass Index ,Survival Rate ,Risk Factors ,Ethnicity ,Humans ,Female ,Menopause ,Aged - Abstract
The purpose of the study was to describe the associations between height and body mass index (BMI) (wt/ht2) and breast cancer incidence and survival among female residents of Hawaii.The study sample is a randomly-selected, multi-ethnic cohort of 17,628 women. A total of 378 incident breast cancer cases were identified via linkage to the Hawaii Tumor Registry over an average follow-up period of 14.9 years. Using age 50 as a cut-point, 86 were considered premenopausal cases, and 292 were postmenopausal. Proportional hazards analysis was used to describe the risks associated with height and BMI, after adjustment for age, education, race/ethnicity, and drinking status. For mortality analyses, there were 34 breast cancer deaths among the 365 breast cancer cases for which staging information was available.The risk of postmenopausal breast cancer was found to increase progressively across approximate tertiles of the distribution of height (P = 0.02 for trend test), with a significantly excess risk among women in the tallest tertile (risk ratio [RR] = 1.5, 95 percent confidence interval [CI] = 1.1-2.1). Baseline levels of BMI were related positively to breast cancer incidence among postmenopausal women, after control for the above covariates (P = 0.01 for trend test). Among postmenopausal women in the highest quintile of the BMI distribution, the RR was 1.5 (CI = 1.0-2.3, P = 0.04). Further analyses indicated the association between BMI and postmenopausal breast cancer incidence was strongest among women aged 65 years and older. After statistical control for the above covariates and stage of disease, pre-morbid levels of BMI were significantly predictive of death from breast cancer, with an approximate nine percent increase in risk per unit increase in BMI (P = 0.01). Compared with women in the lowest two quartiles, the RR among the heaviest women was 2.2 (CI = 0.9-5.4,P = 0.08). Height was not associated with risk of breast cancer mortality.Relative weight may be an important modifiable risk factor for both breast cancer incidence and prognosis. The association between height and breast cancer incidence is more difficult to interpret, but may underscore the importance of early life exposures in the development of breast cancer.
- Published
- 1998
27. Effects of beta-carotene and alpha-tocopherol on bleomycin-induced chromosomal damage
- Author
-
M T, Goodman, B, Hernandez, L R, Wilkens, J, Lee, L, Le Marchand, L Q, Liu, A A, Franke, O, Küçük, and T C, Hsu
- Subjects
Adult ,Male ,Cross-Over Studies ,Mutagenicity Tests ,Chromosome Breakage ,beta Carotene ,Diet ,Bleomycin ,Predictive Value of Tests ,Neoplasms ,Humans ,Vitamin E ,Female ,Lymphocytes ,Mutagens - Abstract
The number of bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes has been proposed as a measure of the sensitivity of an individual to carcinogens. Although "mutagen sensitivity" (clastogenicity) may be a useful biomarker for the identification of individuals at high risk for DNA damage, there is some uncertainty whether the results of this assay can be modified by environmental factors, such as diet. We designed an intervention study to determine whether micronutrient supplementation with beta-carotene and alpha-tocopherol influenced the mutagenicity score among 22 healthy volunteers. This intervention study followed a double-blind, randomized, cross-over design. Chromatid breaks ranged from 0.30 to 2.30 per cell and were uncorrelated with plasma beta-carotene (r = -0.07; P = 0.50) and a-tocopherol (r = -0.01; P = 0.92) levels, after accounting for the time of the measurement. The average number of breaks per cell was similar (P for difference in means = 0.90) among subjects during periods of vitamin supplementation (mean = 0.87 breaks per cell) and placebo (mean = 0.86 breaks per cell), averaged over groups and after adjustment for baseline breaks. Substantial within-person variation may indicate some imprecision in the mutagen sensitivity assessment. Our results suggest that mutagen sensitivity is not affected by plasma levels of beta-carotene or alpha-tocopherol. Although mutagen sensitivity does not appear to be modified by changes in plasma levels of two common antioxidant vitamins, it may be useful for the identification of high-risk individuals for participation in large intervention studies with cancer outcomes.
- Published
- 1998
28. Age and gender differences in the association between MPO 463>A and lung cancer. Results from the genetic susceptibility to environmental carcinogens pooled analysis
- Author
-
E. Frullanti, Stephanie J. London, Emanuela Taioli, Simone Benhamou, Ingolf Cascorbi, Angela Risch, L. Le Marchand, Isabelle Stücker, Margaret R. Spitz, Ping Yang, S. Forti, and Sara Raimondi
- Subjects
Gender Studies ,Age and gender ,Environmental Carcinogen ,Pooled analysis ,business.industry ,Immunology ,Genetic predisposition ,Medicine ,General Medicine ,business ,Lung cancer ,medicine.disease ,Association (psychology) - Published
- 2006
29. Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer
- Author
-
L, Le Marchand, L R, Wilkens, L N, Kolonel, J H, Hankin, and L C, Lyu
- Subjects
Aged, 80 and over ,Male ,Alcohol Drinking ,Rectal Neoplasms ,Hypercholesterolemia ,Smoking ,Hawaii ,Diabetes Complications ,Sex Factors ,Socioeconomic Factors ,Case-Control Studies ,Colonic Neoplasms ,Odds Ratio ,Western World ,Body Constitution ,Humans ,Female ,Obesity ,Energy Intake ,Exercise ,Life Style ,Aged - Abstract
Variation in colorectal cancer rates between countries and within ethnic groups upon migration and/or Westernization suggests a role for some aspects of Western lifestyle in the etiology of this disease. We conducted a population-based case-control study in the multiethnic population of Hawaii to evaluate associations between colorectal cancer and a number of characteristics of the Western lifestyle (high caloric intake, physical inactivity, obesity, smoking, and drinking) and some of their associated diseases. We interviewed in person 698 male and 494 female United States-born or immigrant Japanese, Caucasian, Filipino, Hawaiian, and Chinese patients diagnosed in 1987-1991 with colorectal cancer and 1192 population controls matched on age, sex, and ethnicity. Conditional logistic regression was used to estimate odds ratios adjusting for dietary and nondietary risk factors. Place of birth and duration of residence in the United States were unrelated to colorectal cancer risk. Energy intake (independent of the calorie source) and body mass index were directly associated with risk, and lifetime recreational physical activity was inversely associated with risk. The associations with these factors were independent of each other, additive (on the logistic scale) and stronger in men. When individuals were cross-categorized in relation to the medians of these variables, those with the higher energy intake and body mass index and lower physical activity were at the highest risk (for males, OR, 3.0; 95% confidence interval, 1.8-5.0, and for females, OR, 1.7; 95% confidence interval, 1.0-3.2). Smoking in the distant, as well as recent, past and alcohol use were directly associated with colorectal cancer in both sexes. Individuals with a history of diabetes or frequent constipation were at increased risk for this cancer, whereas past diagnosis of hypercholesterolemia was inversely associated with risk. The findings were consistent between sexes, among ethnic groups, and across stages at diagnosis, making bias an unlikely explanation. These results confirm the data from immigrant studies that suggest that the increase in colorectal cancer risk experienced by Asian immigrants to the United States occurred in the first generation because we found no difference in risk between the immigrants themselves and subsequent generations. They also agree with recent findings that suggest that high energy intake, large body mass, and physical inactivity independently increase risk of this disease and that a nutritional imbalance, similar to the one involved in diabetes, may lead to colorectal cancer.
- Published
- 1997
30. A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii (United States): lipids and foods of animal origin
- Author
-
L, Le Marchand, L R, Wilkens, J H, Hankin, L N, Kolonel, and L C, Lyu
- Subjects
Adult ,Male ,China ,Meat ,Philippines ,Cultural Diversity ,Adenocarcinoma ,Dietary Fats ,Hawaii ,White People ,Logistic Models ,Japan ,Risk Factors ,Case-Control Studies ,Odds Ratio ,Humans ,Female ,Colorectal Neoplasms - Abstract
Temporal trend and migrant studies have indicated that the etiology of colorectal cancer is predominantly environmental and, hence, modifiable. Animal fat intake has been frequently, but inconsistently, associated with the risk of this disease. We conducted a population-based case-control study in Hawaii (United States) among ethnic groups at different risks of the disease to evaluate the role of dietary lipids and foods of animal origin on the risk of colorectal cancer. We interviewed 698 male and 494 female Japanese, Caucasian (White), Filipino, Hawaiian, and Chinese patients diagnosed during 1987-91 with pathologically confirmed adenocarcinoma of the colon or rectum, and 1,192 population controls matched to cases on age, gender and ethnicity. Odds ratios (OR), adjusted for caloric intake and other dietary and non-dietary risk factors, were estimated using conditional logistic regression. Intakes of total fat, saturated fat (S) and polyunsaturated fat (P) were not related to the risk of colorectal cancer. However, an inverse association was found for the P/S ratio, with ORs of 0.6 in both genders (95 percent confidence interval [CI] = 0.4-1.0 for males; CI = 0.3-0.9 for females) for the highest compared with the lowest quartile (P0.05 for trend). Intakes of red meat and processed meat were associated with the risk of cancer in the right colon and rectum, respectively, in men only. Fat-trimmed red meat and fish intakes were not related to risk. Chicken eaten without skin was associated inversely with risk in both genders. The strongest association was found for eggs, with an OR of 2.7 (CI = 1.7-4.0) and 2.3 (CI = 1.4-3.7) for the highest compared with the lowest quartile of intake in men and women, respectively (P0.001 for trend). This association was dose-dependent, not explained by known confounders or other dietary variables, and was very consistent between genders, among ethnic groups, and across all segments of the large bowel. These data suggest that the ratio of polyunsaturated to saturated fat may be a better indicator of colorectal cancer risk than the absolute amount of specific fats in the diet. They also suggest that eggs and, possibly, untrimmed red meat and processed meat increase, and chicken eaten without skin decreases, colorectal cancer risk.
- Published
- 1997
31. Predictors of N-acetyltransferase activity: should caffeine phenotyping and NAT2 genotyping be used interchangeably in epidemiological studies?
- Author
-
L, Le Marchand, L, Sivaraman, A A, Franke, L J, Custer, L R, Wilkens, A F, Lau, and R V, Cooney
- Subjects
Adult ,Male ,Genotype ,Arylamine N-Acetyltransferase ,Acetylation ,Middle Aged ,Polymerase Chain Reaction ,Phenotype ,Adenomatous Polyposis Coli ,Risk Factors ,Caffeine ,Humans ,Female ,Alleles ,Aged - Abstract
To determine whether NAT2 genotyping could be used interchangeably with caffeine phenotyping in assessing N-acetyltransferase activity in epidemiological studies, sources of interindividual variability in N-acetyltransferase activity were assessed among 90 subjects of various ethnic backgrounds in Hawaii. Forty-three subjects were patients with in situ colorectal cancer treated by polypectomy, and 47 were healthy population controls. Subjects were administered a lifestyle questionnaire and were evaluated for N-acetyltransferase activity by caffeine phenotyping. NAT2 genotype was also assessed by PCR amplification of peripheral leukocyte DNA for the M1, M2, and M3 variant alleles. Fifty-four % of the overall variation in acetylation activity was explained by the three genotype categories (homozygous variant, heterozygous, and homozygous wild-type). This proportion was reduced to 42% when genotype was modeled using only two categories ("slow" being homozygous variant; "rapid" being all others). Use of gout medications (probenecid or allopurinol), consumption of heavily browned fish, and P450IA2 activity (also measured by caffeine phenotyping), together explained another 11% of the variance. No association was found between acetylation activity and sex; race; age; education; smoking; physical activity; weight; consumption of coffee, alcohol, red meat, processed meat, and cruciferous vegetables; or use of menopausal estrogens, after taking genotype into account. Results were similar for colorectal cancer patients and controls. Considerable variation in acetylation activity was observed within the homozygous wild-type group. This study suggests that the use of genotyping, instead of phenotyping, to assess the association of acetylation with cancer risk is unlikely to introduce major misclassification or bias, especially when the three genotype categories are modeled and the sample size is large. However, when the rapid acetylation phenotype is the at-risk group (e.g., when studying colon career), phenotyping appears judicious given the variability in acetylation activity within this group.
- Published
- 1996
32. Seasonal variations in plasma micronutrients and antioxidants
- Author
-
R V, Cooney, A A, Franke, J H, Hankin, L J, Custer, L R, Wilkens, P J, Harwood, and L, Le Marchand
- Subjects
Adult ,Male ,Nutritional Requirements ,Ascorbic Acid ,Feeding Behavior ,Middle Aged ,Carotenoids ,Antioxidants ,Hawaii ,Trace Elements ,Cholesterol ,Reference Values ,Humans ,Vitamin E ,Female ,Seasons ,Vitamin A ,Triglycerides - Abstract
Plasma samples were collected at monthly intervals for a period of 1 year from a group of healthy nonsmoking men and women (n = 21) living in Honolulu, HI. Analysis of plasma cholesterol and triglyceride levels showed marked seasonal variations, with higher mean levels in winter months and lower values in the summer. Cholesterol and triglycerides were highly and inversely correlated with plasma levels of the provitamin A carotenoids. Mean beta- and alpha-carotene levels were highest in late summer and fall. Plasma retinol levels were significantly lower in the summer and higher in the winter. Variations (either between individuals or seasonally) in plasma retinol were unrelated to plasma provitamin A carotenoid levels. Plasma levels of alpha-tocopherol, gamma-tocopherol, beta-cryptoxanthin, and lutein were also higher in the winter and lower in the summer. Significant seasonal correlations, both positive and negative, with environmental variables, such as temperature, solar UV radiation, and rainfall, are noted for many of these plasma micronutrients. The number of samples required to accurately characterize long-term plasma levels for an individual generally ranged from 1 to 4. However, plasma retinol levels exhibited the highest ratio of intra- to interindividual variability, suggesting the need for multiple sampling (8 samples) for this micronutrient. Some of this variability for retinol was associated with seasonal changes. Assessment by a diet history of food and supplement intake of micronutrients and phytochemicals for 1 year showed good agreement with 1-year mean plasma levels for most carotenoids, vitamin C, and alpha-tocopherol. Retinol, gamma-tocopherol, cholesterol, and triglyceride levels in plasma were unrelated to estimates of dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
33. Correlations between mutagen sensitivity and plasma nutrient levels of healthy individuals
- Author
-
O, Küçük, A, Pung, A A, Franke, L J, Custer, L R, Wilkens, L, Le Marchand, C M, Higuchi, R V, Cooney, and T C, Hsu
- Subjects
Adult ,Chromosome Aberrations ,Male ,Mutagenicity Tests ,Ascorbic Acid ,Feeding Behavior ,Middle Aged ,Carotenoids ,Antioxidants ,Hawaii ,Trace Elements ,Bleomycin ,Cholesterol ,Reference Values ,Risk Factors ,Humans ,Vitamin E ,Female ,Seasons ,Vitamin A ,Triglycerides ,Aged - Abstract
Increased mutagen sensitivity and decreased intake of antioxidant-rich fruits and vegetables have been associated with an increased risk of upper aerodigestive tract cancers. The objective of this study was to investigate the intraindividual variation in mutagen sensitivity and its possible correlation with plasma nutrient levels in a group of 25 healthy individuals in Hawaii. Mutagen sensitivity, as assessed by bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes and plasma nutrient levels were measured monthly for 11 months. The monthly numbers of chromosomal breaks/cell ranged from 0.04 to 0.80 and showed considerable intraindividual variation. Based on individual means, significant inverse correlations were found between mutagen sensitivity scores and the plasma levels of alpha-carotene (r = -0.64), total carotenoids (r = -0.41), and ascorbic acid (r = -0.40). There were also significant inverse associations between monthly mean plasma levels of alpha-carotene (r = -0.58), beta-carotene (r = -0.76) and total carotenoids (r = -0.72) and monthly mean chromosomal breaks. In contrast, there was a significant positive correlation between monthly mean plasma triglyceride level (r = 0.60) and monthly mean mutagen sensitivity. These results suggest that mutagen sensitivity as assessed by the bleomycin assay may be influenced by plasma levels of certain nutrients and could potentially be modified by dietary interventions or micronutrient supplementation.
- Published
- 1995
34. CYP1A1 genetic polymorphisms and in situ colorectal cancer
- Author
-
L, Sivaraman, M P, Leatham, J, Yee, L R, Wilkens, A F, Lau, and L, Le Marchand
- Subjects
Adult ,Male ,Base Sequence ,Cytochrome P-450 Enzyme System ,Case-Control Studies ,Molecular Sequence Data ,Humans ,Female ,Polycyclic Compounds ,Middle Aged ,Colorectal Neoplasms ,Polymorphism, Restriction Fragment Length ,Aged - Abstract
Numerous studies have associated colorectal adenoma with smoking and large bowel cancer with consumption of foods potentially containing polycyclic aromatic hydrocarbons. Enhanced metabolic activation of polycyclic aromatic hydrocarbons has recently been observed in homozygotes for a MspI mutation in the 3'-end of CYP1A1. We conducted a population-based case-control study to investigate whether CYP1A1 polymorphisms were related to colorectal cancer risk. Using polymerase chain reaction-based methods, we assessed the frequency of the MspI polymorphism in the 3'-end of CYP1A1 and another mutation in exon 7 of the gene (Ile-Val polymorphism) among 43 patients with in situ adenocarcinoma of the large bowel and 129 population controls. Homozygosity for the MspI mutant genotype was found to be positively associated with in situ colorectal cancer in Japanese (P = 0.008) and Hawaiians/part-Hawaiians (P0.001), whereas the study lacked power to detect a similar association in Caucasians. The odds ratio for the homozygous variant genotype compared to the heterozygous and wild-type genotypes was 7.9 (95% confidence interval, 1.4-44.4) in Japanese. A similar association was suggested for the exon 7 mutation homozygosity in Japanese, as the two polymorphisms are in genetic disequilibrium. Thus, this study suggests a potentially important role for CYP1A1 and polycyclic aromatic hydrocarbons in the etiology of colorectal cancer in populations with a high gene frequency.
- Published
- 1994
35. A pilot study on the use of plasma carotenoids and ascorbic acid as markers of compliance to a high fruit and vegetable dietary intervention
- Author
-
L, Le Marchand, J H, Hankin, F S, Carter, C, Essling, D, Luffey, A A, Franke, L R, Wilkens, R V, Cooney, and L N, Kolonel
- Subjects
Male ,Lung Neoplasms ,Nutritional Sciences ,Lutein ,Pilot Projects ,Ascorbic Acid ,Middle Aged ,Carotenoids ,Diet Records ,Lycopene ,Head and Neck Neoplasms ,Fruit ,Vegetables ,Carcinoma, Squamous Cell ,Humans ,Patient Compliance ,Female ,Seasons ,Biomarkers ,Aged - Abstract
The authors examined the feasibility of using plasma carotenoids and ascorbic acid as markers of compliance for dietary intervention trials aimed at increasing the quantity and variety of the fruit and vegetable intake of free-living individuals. Nineteen former cancer patients who had been successfully treated for a stage I or II squamous cell carcinoma of the mouth, pharynx, larynx, or lung were recruited. Subjects served as their own controls. However, in order to detect any seasonal trends, 4 individuals among the 19 were randomized to a nonintervention group. Subjects in the intervention group were counseled by dietitians with the goal of increasing their intake of fruits and vegetables to eight servings/day (1 serving each of dark green vegetables, yellow-orange vegetables, tomato products, and other vegetables; 3 servings of vitamin C-rich fruits; and 1 serving of other fruits). Subjects in the nonintervention group were advised to follow their usual diet. Three-day measured food records kept at base line and after 3 months of intervention, as well as unannounced 24-h dietary recalls, documented an increase in mean fruit and vegetable intake from 4.2 to 9.5 servings daily in the intervention group. A concomitant increase of 29% was observed in total plasma carotenoids (P = 0.02), with increases of 25% for plasma lycopene (P = 0.06), 31% for plasma lutein (P = 0.002), 39% for plasma beta-carotene (P = 0.01), and 57% for plasma alpha-carotene (P = 0.01). Mean plasma levels of ascorbic acid increased by 27% (P0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
36. Use of breath hydrogen and methane as markers of colonic fermentation in epidemiological studies: variability in excretion
- Author
-
L R, Wilkens, L, Le Marchand, P, Harwood, and R V, Cooney
- Subjects
Aged, 80 and over ,Cross-Cultural Comparison ,Male ,Asian ,Smoking ,Feeding Behavior ,Middle Aged ,Hawaii ,Breath Tests ,Reference Values ,Risk Factors ,Case-Control Studies ,Colonic Neoplasms ,Fermentation ,Biomarkers, Tumor ,Humans ,Mass Screening ,Female ,Methane ,Aged ,Hydrogen - Abstract
Breath hydrogen and methane are specific end products of colonic fermentation, a process which may play a protective role against colon cancer. To assess the possibility of using these markers in epidemiological studies, we characterized the intra- and intersubject variability of breath hydrogen and methane excretion over 15 consecutive days among 32 men and women of various ethnic backgrounds (16 Asians, 8 Caucasians, 8 Hawaiians). Participants were asked to collect four end-expiratory samples each day, which we had shown previously would optimally characterize daily hydrogen excretion. There was substantial within-subject variation in breath hydrogen over the study, although breath methane levels were more constant over time. We found that about 4 days of measurement of breath hydrogen and 1 day of measurement for breath methane are required to correctly characterize individuals according to their long-term excretion of these gases. This was true for Asians and non-Asians. Although breath methane appears to be more practical to measure, it is a less sensitive marker of colonic fermentation than breath hydrogen. Whereas all subjects excreted hydrogen, only 28% of the subjects excreted methane, and methane excretor status of a few participants varied during the study. Because the breath test is noninvasive and reliable, we tested the multiple day collection protocol among colon cancer patients and controls and found it to be well accepted. We conclude that it is practical to measure breath hydrogen and methane in large epidemiological studies conducted at the individual level. The potential use for these markers is discussed.
- Published
- 1994
37. Intake of specific carotenoids and lung cancer risk
- Author
-
L, Le Marchand, J H, Hankin, L N, Kolonel, G R, Beecher, L R, Wilkens, and L P, Zhao
- Subjects
Male ,Lung Neoplasms ,Matched-Pair Analysis ,Carotenoids ,Diet Surveys ,Hawaii ,Diet ,Logistic Models ,Risk Factors ,Case-Control Studies ,Population Surveillance ,Vegetables ,Odds Ratio ,Humans ,Female ,Food Analysis - Abstract
Using newly available food composition data for carotenoids, the authors reanalyzed a population-based case-control study of diet and lung cancer conducted in Hawaii in 1983-1985 (L. Le Marchand et al., J. Natl. Cancer Inst., 81: 1158-1164, 1989). The analysis included interviews with 230 men and 102 women with lung cancer and 597 men and 268 women as controls, frequency-matched to the patients by age and sex. A previously validated quantitative diet history assessed the usual intake of foods rich in carotenoids. After adjusting for smoking and other covariates, no association was found with lung cancer risk for dietary lycopene or beta-cryptoxanthin intake, whereas dose-dependent inverse associations of comparable magnitude were found for dietary beta-carotene, alpha-carotene, and lutein. When subjects were cross-classified by their joint intakes of the latter three carotenoids, those who had a high intake (median) for all three had the lowest risk for lung cancer. In a similar two-way interaction analysis, the previously reported inverse association of lung cancer with vegetable consumption in these data was found to be stronger than that with intake of these three carotenoids. Consistent with our previous findings, this analysis provides further evidence for a protective effect of certain carotenoids against lung cancer and for the greater protection afforded by consuming a variety of vegetables compared to only foods rich in a particular carotenoid.
- Published
- 1993
38. Ethnic differences in the lung cancer risk associated with smoking
- Author
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L, Le Marchand, L R, Wilkens, and L N, Kolonel
- Subjects
Adult ,Aged, 80 and over ,Male ,China ,Lung Neoplasms ,Incidence ,Philippines ,Smoking ,Middle Aged ,Hawaii ,White People ,Logistic Models ,Sex Factors ,Japan ,Risk Factors ,Case-Control Studies ,Ethnicity ,Humans ,Female ,Aged - Abstract
Mortality trends and ecological data strongly suggest that the lung cancer risk associated with smoking is greater among Hawaiians than among the other ethnic groups in Hawaii. The authors combined data from two consecutive population-based case-control studies to formally test this hypothesis among 740 cases and 1616 controls. A multiple logistic regression analysis adjusting for pack-years of smoking, occupation, education, and age revealed that Hawaiian, Filipino, and Caucasian male smokers were at 121%, 53%, and 46% greater risk for lung cancer than Japanese male smokers. These risk differences were statistically significant, were consistent across sexes and histological types, and were not explained by the type of cigarettes, the level of inhalation, or by cholesterol or beta-carotene intake. Additionally, an increased lung cancer risk unrelated to smoking was observed among Chinese women. The possibility that other dietary antioxidants and/or genetic risk factors are responsible for these ethnic differences needs to be investigated.
- Published
- 1992
39. [Cancer in Japanese migrants to Hawaii: interaction between genes and environment]
- Author
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L, Le Marchand and L N, Kolonel
- Subjects
Male ,Lung Neoplasms ,Japan ,Neoplasms ,Colonic Neoplasms ,Humans ,Female ,Genetic Predisposition to Disease ,Environmental Exposure ,Emigration and Immigration ,Hawaii - Abstract
This paper describes the progressive changes in cancer incidence that have been observed among Japanese after their migration to Hawaii. It reviews descriptive and analytic epidemiologic data suggesting a role for genetic susceptibilities in explaining the high risk of Japanese for colon cancer and their low risk for lung cancer, when compared to Caucasians. Differences in certain pharmacogenetic polymorphisms may explain these risk patterns. This research may lead to a better characterization of cancer risk at the individual level and, consequently, to improved methods of prevention.
- Published
- 1992
40. An analytical method for assessing patterns of familial aggregation in case-control studies
- Author
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L P, Zhao and L, Le Marchand
- Subjects
Adult ,Male ,Statistics as Topic ,Middle Aged ,Hawaii ,Bias ,Risk Factors ,Case-Control Studies ,Ethnicity ,Odds Ratio ,Humans ,Regression Analysis ,Female ,Colorectal Neoplasms ,Epidemiologic Methods ,Aged - Abstract
This paper describes an analytical method that is used to assess patterns of disease aggregation within family based on family history information collected in case-control studies. In such a study, cases and controls are thought of as probands whose relatives are identified, and relatives' phenotypes and other covariates such as age, sex, and genealogical relationship with the probands are recorded. By modeling the dependence of relatives' phenotypes on case-control status and other covariates, this method yields adjusted odds ratios that quantify familial aggregation. The estimated standard errors are obtained for statistical inference since the method acknowledges the potential correlations between relatives' phenotypes by using the estimating equations technique. In population-based case-control studies, the estimates and statistical inferences are generalizable to the general population. To illustrate this method, we analyzed a case-control study of colorectal cancer involving 5,190 relatives of 792 cases and 4,478 relatives of 680 population-based controls conducted in Hawaii. Although detailed results will be presented elsewhere, the colorectal cancer was found to aggregate within family with an odds ratio of 2.74 (95% confidence interval (CI): 1.78-4.21). Among parents, the odds ratio for familial aggregation was 2.38 (95% CI: 1.25-4.54). The corresponding value for siblings was 3.09 (95% CI: 1.87-5.11). It was also found that the odds ratio increases from about 2.00 for relatives of the probands who were 50 years or older to 7.66 and 12.84 for relatives of the probands who were between 40 and 50 years and under 40 years, respectively, suggesting that the familial aggregation of colorectal cancer decreases as probands' age increases.
- Published
- 1992
41. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis.
- Author
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S. Anttila, I. Kalina, L. Le Marchand, S.J. London, A. Rannug, M. Romkes, J. Salagovic, B. Schoket, L. Gaspari, E. Taioli, R.J. Hung, P. Boffetta, J. Brockmöller, D. Butkiewicz, I. Cascorbi, M.L. Clapper, S. Garte, A. Haugen, and A. Hirvonen
- Subjects
GENETIC polymorphisms ,CYTOCHROMES ,LUNG cancer - Abstract
Polymorphisms for genes encoding the metabolic enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) might contribute to the variability in individual susceptibility to lung cancer. The role of CYP1A1 and GSTM1 in lung carcinogenesis might be more important at low levels of exposure to carcinogens. Non-smokers represent a population at low exposure, however, they are often overlooked because of the small number of cases. We therefore conducted a pooled analysis of 14 case-control studies on lung cancer in Caucasian non-smokers with comparable information on genetic polymorphisms included in the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. We pooled the raw data from a total of 302 cases and 1631 controls with random effects models. We also evaluated the possibility of inclusion bias and conducted influence analyses. The odds ratio (OR) of lung cancer for the variant CYP1A1 Ile
462 Val polymorphism (Ile/Val, Val/Val) was 2.99 [95% confidence interval (95%CI) 1.51-5.91]; this effect was stronger on lung adenocarcinoma (OR 4.85, 95%CI 2.03-11.6). After excluding outlying or imprecise studies, we did not observe a significant effect of the CYP1A1 MspI (T3801 C) polymorphism or GSTM1 null genotype (OR 1.20, 95%CI 0.89-1.63). Furthermore, our analyses suggested a combined effect of the CYP1A1 Ile462 Val polymorphism and GSTM1 null genotype. The OR for the combination of the CYP1A1 Ile462 Val variant and GSTM1 null genotype was 4.67 (95%CI 2.00-10.9) compared with the concurrent presence of the CYP1A1 wild-type and GSTM1 non-null genotype. We did not observe a modification of the effect of the GSTM1 null genotype according to exposure to environmental tobacco smoke and urban/rural residence. Our study therefore suggests that the CYP1A1 Ile462 Val variant allele might play a role in lung carcinogenesis among non-smokers, possibly in combination with the GSTM1 null genotype. [ABSTRACT FROM AUTHOR]- Published
- 2003
42. Sex ratio of offspring of patients with prostatic cancer
- Author
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L, Le Marchand, C N, Yoshizawa, and L N, Kolonel
- Subjects
Male ,Letter ,Reproduction ,Humans ,Prostatic Neoplasms ,Female ,Sex Ratio - Published
- 1986
43. Seasonal variation in birthdates of men with testicular cancer
- Author
-
L N Kolonel and L Le Marchand
- Subjects
Gynecology ,Male ,medicine.medical_specialty ,Periodicity ,Epidemiology ,business.industry ,Public Health, Environmental and Occupational Health ,Seasonality ,medicine.disease ,Testicular Neoplasms ,medicine ,Humans ,Seasons ,business ,Testicular cancer ,Research Article - Published
- 1987
44. The epidemiology of colon cancer and dietary fat
- Author
-
L N, Kolonel and L, Le Marchand
- Subjects
Dietary Fiber ,Male ,Risk ,Cocarcinogenesis ,Meat ,Dietary Fats ,Feces ,Colonic Neoplasms ,Humans ,Female ,Steroids ,Energy Intake ,Epidemiologic Methods ,Biotransformation ,Diagnosis-Related Groups ,Mutagens - Published
- 1986
45. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
- Author
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Jian Song, David C. Gotley, Naohiro Nishida, Stephen N. Thibodeau, Gijs A. Patijn, Ingrid de Vries, Mike Churchman, Roxana S. Redis, Ken Yamamoto, Ramana V. Davuluri, Itsuki Taniguchi, Berna Beverloo, Maarit Tiirikainen, Imad Shureiqi, Xinna Zhang, Anieta M. Sieuwerts, Roberta Gafà, Graham Casey, Stanley R. Hamilton, James W. Welsh, Masaki Mori, Massimo Negrini, Franziska Haderk, Janneke F. van Galen, Koshi Mimori, Riccardo Spizzo, Milena S. Nicoloso, Cristina Ivan, Marcos R. Estecio, Steven Gallinger, Riccardo Fodde, Ian Tomlinson, Loic Le Marchand, Vikas Bhardwaj, Min-Ae Song, Sendurai A. Mani, George A. Calin, Wei Zhang, Guillermo Garcia-Manero, Asha S. Multani, Manuela Ferracin, Hui Ling, Ioana Berindan-Neagoe, Yaser Atlasi, Masayoshi Shimizu, Subrata Sen, Giovanni Lanza, Zhiyi Guo, Maryam Shariati, Elisa Barbarotto, John A. Foekens, John W.M. Martens, Scott Kopetz, Pathology, Clinical Genetics, Medical Oncology, H. Ling, R. Spizzo, Y. Atlasi, M. Nicoloso, M. Shimizu, R. S. Redi, N. Nishida, R. Gafa, J. Song, Z. Guo, C. Ivan, E. Barbarotto, I. De Vrie, X. Zhang, M. Ferracin, M. Churchman, J. F. van Galen, B. H. Beverloo, M. Shariati, F. Haderk, M. R. Estecio, G. Garcia-Manero, G. A. Patijn, D. C. Gotley, V. Bhardwaj, I. Shureiqi, S. Sen, A. S. Multani, J. Welsh, K. Yamamoto, I. Taniguchi, M.-A. Song, S. Gallinger, G. Casey, S. N. Thibodeau, L. Le Marchand, M. Tiirikainen, S. A. Mani, W. Zhang, R. V. Davuluri, K. Mimori, M. Mori, A. M. Sieuwert, J. W. M. Marten, I. Tomlinson, M. Negrini, I. Berindan-Neagoe, J. A. Foeken, S. R. Hamilton, G. Lanza, S. Kopetz, R. Fodde, and G. A. Calin
- Subjects
Male ,Transcription, Genetic ,Colorectal cancer ,Transcription Factor 7-Like 1 Protein ,SNP RS6983267 ,BETA-CATENIN ,COLORECTAL-CANCER ,Metastasis ,Mice ,0302 clinical medicine ,Chromosome instability ,Transcriptional regulation ,TRANSCRIPTION ,Neoplasm Metastasis ,Wnt Signaling Pathway ,Genetics (clinical) ,Genetics ,Regulation of gene expression ,0303 health sciences ,Wnt signaling pathway ,Non-coding RNA ,3. Good health ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Female ,RNA, Long Noncoding ,Chromosomes, Human, Pair 8 ,colorectal cancer ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,NO ,target ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Cell Line, Tumor ,Chromosomal Instability ,microRNA ,expression ,C-MYC ,medicine ,BREAST-CANCER ,Animals ,Humans ,030304 developmental biology ,HUMAN-CELLS ,Research ,medicine.disease ,APC ,MicroRNAs ,Case-Control Studies ,Cancer research ,protein ,colorectal cancer, expression, microRNas, protein, target - Abstract
The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR–17–5p, and miR–20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk.
- Published
- 2013
46. Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.
- Author
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Wu AH, Wu J, Tseng C, Stram DO, Shariff-Marco S, Larson T, Goldberg D, Fruin S, Jiao A, Inamdar PP, Ihenacho U, Le Marchand L, Wilkens L, Haiman C, Ritz B, and Cheng I
- Abstract
Purpose: Recent studies suggested fine particulate matter (PM
2.5 ) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse., Materials and Methods: Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors., Results: Satellite-based PM2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m3 , 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM2.5 -associations ( Pheterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM2.5 (HR per 10 μg/m3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064)., Conclusion: Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM2.5 exposure.- Published
- 2024
- Full Text
- View/download PDF
47. Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.
- Author
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Hazelwood E, Lopez Manzano C, Vincent EE, Albanes D, Bishop DT, Le Marchand L, Ulrich CM, Peters U, Murphy G, Samadder NJ, Anderson L, Gunter MJ, Murphy N, Van Guelpen B, and Papadimitriou N
- Abstract
Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis., Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied., Results: We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC., Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk., Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.
- Published
- 2024
- Full Text
- View/download PDF
48. Breast, Colorectal, and Prostate Cancer Incidence among Filipino Americans by Generational Status in the Multiethnic Cohort Study.
- Author
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Abe JV, Legaspi J, Guillermo C, Bogumil D, Setiawan VW, Le Marchand L, Hernandez BY, Wilkens LR, and Maskarinec G
- Subjects
- Humans, Male, Female, Incidence, Middle Aged, Aged, Hawaii epidemiology, Cohort Studies, Philippines ethnology, California epidemiology, Prospective Studies, Adult, Colorectal Neoplasms epidemiology, Colorectal Neoplasms ethnology, Prostatic Neoplasms ethnology, Prostatic Neoplasms epidemiology, Breast Neoplasms ethnology, Breast Neoplasms epidemiology, Asian statistics & numerical data
- Abstract
Background: Filipino Americans constitute 12% and 4% of the respective populations of Hawaii and California, with a large proportion of immigrants experiencing increasing cancer rates. This study investigated the incidence of colorectal, breast, and prostate cancers by generational status in the Multiethnic Cohort., Methods: We analyzed 10,495 Filipino Multiethnic Cohort first-, second-, and third-generation participants, in which 26.8% were of mixed race and ethnicity. Linkage to statewide cancer registries identified 375 breast, 249 colorectal, and 436 prostate cancer incident cases. Cox models were used to calculate HRs and 95% confidence intervals (CI) for the association between generational status and cancer incidence. Models were adjusted for age at cohort entry and cancer-specific covariates that were chosen based on stepwise regression., Results: Compared with the first generation, colorectal cancer showed a significantly higher incidence in the second and third generations with respective HRs of 1.43 (95% CI, 1.04, 1.98) and 1.76 (95% CI, 1.29, 2.38). This association was attenuated after adjustment for relevant covariates. Breast cancer incidence was elevated in the third versus first generation (HR = 1.29; 95% CI, 1.01, 1.63) even in the fully adjusted model, whereas little difference was observed for prostate cancer., Conclusions: In this prospective study, we found differences in incidence by generational status, specifically colorectal cancer among men and female breast cancer., Impact: Understanding behavioral changes due to acculturation is warranted to mitigate cancer risks in migrant populations., (©2024 American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
49. Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.
- Author
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Tin Tin S, Smith-Byrne K, Ferrari P, Rinaldi S, McCullough ML, Teras LR, Manjer J, Giles G, Le Marchand L, Haiman CA, Wilkens LR, Chen Y, Hankinson S, Tworoger S, Eliassen AH, Willett WC, Ziegler RG, Fuhrman BJ, Sieri S, Agnoli C, Cauley J, Menon U, Fourkala EO, Rohan TE, Kaaks R, Reeves GK, and Key TJ
- Subjects
- Adult, Female, Humans, Middle Aged, Alcohol Dehydrogenase genetics, Breast Neoplasms blood, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cohort Studies, Cross-Sectional Studies, Estradiol blood, Estradiol metabolism, Postmenopause blood, Progesterone blood, Progesterone metabolism, Testosterone blood, Testosterone metabolism, Alcohol Drinking adverse effects, Alcohol Drinking blood, Alcohol Drinking metabolism, Gonadal Steroid Hormones blood, Gonadal Steroid Hormones metabolism, Mendelian Randomization Analysis, Premenopause blood, Sex Hormone-Binding Globulin metabolism, Sex Hormone-Binding Globulin analysis
- Abstract
Background: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes., Methods: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984)., Results: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively)., Conclusions: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
- Published
- 2024
- Full Text
- View/download PDF
50. Characterization of additive gene-environment interactions for colorectal cancer risk.
- Author
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Thomas CE, Lin Y, Kim M, Kawaguchi ES, Qu C, Um CY, Lynch BM, Van Guelpen B, Tsilidis K, Carreras-Torres R, van Duijnhoven FJ, Sakoda LC, Campbell PT, Tian Y, Chang-Claude J, Bézieau S, Budiarto A, Palmer JR, Newcomb PA, Casey G, Le Marchand L, Giannakis M, Li CI, Gsur A, Newton C, Obón-Santacana M, Moreno V, Vodicka P, Brenner H, Hoffmeister M, Pellatt AJ, Schoen RE, Dimou N, Murphy N, Gunter MJ, Castellví-Bel S, Figueiredo JC, Chan AT, Song M, Li L, Bishop DT, Gruber SB, Baurley JW, Bien SA, Conti DV, Huyghe JR, Kundaje A, Su YR, Wang J, Keku TO, Woods MO, Berndt SI, Chanock SJ, Tangen CM, Wolk A, Burnett-Hartman A, Wu AH, White E, Devall MA, Díez-Obrero V, Drew DA, Giovannucci E, Hidaka A, Kim AE, Lewinger JP, Morrison J, Ose J, Papadimitriou N, Pardamean B, Peoples AR, Ruiz-Narvaez EA, Shcherbina A, Stern MC, Chen X, Thomas DC, Platz EA, Gauderman WJ, Peters U, and Hsu L
- Abstract
Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure., Methods: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk., Results: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility., Conclusions: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention., Competing Interests: Conflict of Interest: SB Gruber: Brogent International LLC, co-founder, not related to submitted work. All other authors do not have any conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
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