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L Le Marchand

Publications and source records attributed to L Le Marchand.

At least 37 records · Page 2Linked to original sources
PubMed1999

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

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

Alleles↗
PubMed1999

Effects of marinating with Asian marinades or western barbecue sauce on PhIP and MeIQx formation in barbecued beef.

Heterocyclic aromatic amines (HAAs), a group of chemicals formed during high-temperature cooking of meat and fish, are potent mutagens and are suspected to play a role in colorectal cancer. A recent study suggested that marinating meat may offer a way to reduce HAA formation. Hawaii's diverse ethnic populations, which are at various risks of colorectal cancer, often use traditional marinades when cooking meat. We compared the HAA content of beef steaks marinated overnight with teriyaki sauce, turmeric-garlic sauce, or commercial honey barbecue sauce with that of unmarinated steaks. The levels of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were determined by liquid-liquid extraction and gas chromatography-mass spectrometry. Beef steaks marinated with teriyaki sauce had 45% and 67% lower PhIP level at 10 minutes (p = 0.002) and 15 minutes (p = 0.001) of cooking time as well as 44% and 60% lower MeIQx levels at 10 minutes (p = 0.008) and 15 minutes (p = 0.001), respectively, than unmarinated meat. Lower levels of PhIP and MeIQx were also observed in meat marinated with turmeric-garlic sauce. In contrast, marinating with barbecue sauce caused a 2.9- and 1.9-fold increase in PhIP (p < or = 0.005) and a 4- and 2.9-fold increase in MeIQx (p < or = 0.001) at 10 and 15 minutes, respectively. Differences in the mutagenic activities of marinated and unmarinated steaks, as measured by the Ames assay, paralleled the differences in PhIP and MeIQx levels. Future studies should test the effects of specific ingredients, including the water content of marinades, and the effect of reapplying barbecue sauce during cooking (to reduce charring) on HAA formation.

Asia↗
PubMed1999

Correlates of intentions to obtain genetic counseling and colorectal cancer gene testing among at-risk relatives from three ethnic groups.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed1999

Underreporting of family history of colon cancer: correlates and implications.

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.

Adult↗
PubMed1999

Independent and joint effects of family history and lifestyle on colorectal cancer risk: implications for prevention.

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.

Age Factors↗
PubMed1998

Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens.

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.

Adult↗
PubMed1998

Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed1998

Effects of beta-carotene and alpha-tocopherol on bleomycin-induced chromosomal damage.

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.

Adult↗
PubMed1998

A simple mouthwash method for obtaining genomic DNA in molecular epidemiological studies.

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.

Adult↗
PubMed1997

Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer.

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.

Aged↗
PubMed1997

A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii (United States): lipids and foods of animal origin.

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 (P < 0.05 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 (P < 0.001 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.

Adenocarcinoma↗
PubMed1997

Dietary fiber and colorectal cancer risk.

We conducted a population-based case-control study among different ethnic groups in Hawaii to evaluate the role of various types and components of fiber, as well as micronutrients and foods of plant origin, on the risk of colorectal cancer. We administered personal interviews to 698 male and 494 female Japanese, Caucasian, Filipino, Hawaiian, and Chinese cases diagnosed during 1987-1991 with adenocarcinoma of the colon or rectum and to 1,192 population controls matched to cases by age, sex, and ethnicity. We used conditional logistic regression to estimate odds ratios, adjusted for caloric intake and other covariates. We found a strong, dose-dependent, inverse association in both sexes with fiber intake measured as crude fiber, dietary fiber, or nonstarch polysaccharides. We found inverse associations of similar magnitude for the soluble and insoluble fiber fractions and for cellulose and noncellulosic polysaccharides. This protective effect of fiber was limited to fiber from vegetable sources, with an odds ratio of 0.6 (95% confidence interval = 0.4-0.9) and 0.5 (95% confidence interval = 0.3-0.7) for the highest compared with the lowest quartile of intake for men and women, respectively. We found associations of the same magnitude for soluble and insoluble vegetable fiber, but no clear association with fiber from fruits or cereals. This pattern was consistent between sexes, across segments of the large bowel (right colon, left colon, and rectum), and among most ethnic groups. The effect of vegetable fiber may be independent of the effects of other phytochemicals, since the effect estimates remained unchanged after further adjustment for other nutrients. Intakes of carotenoids, light green vegetables, yellow-orange vegetables, broccoli, corn, carrots, bananas, garlic, and legumes (including soy products) were inversely associated with risk, even after adjustment for vegetable fiber. The data support a protective role of fiber from vegetables against colorectal cancer, which appears independent of its water solubility property and of the effects of other phytochemicals. The data also indicate that certain vegetables and fruits may be protective against this disease through mechanisms other than their fiber content.

Adenocarcinoma↗
PubMed1997

Lifestyle and nutritional correlates of cytochrome CYP1A2 activity: inverse associations with plasma lutein and alpha-tocopherol.

Cytochrome CYP1A2, a liver enzyme responsible for the metabolic activation of a number of putative human carcinogens, exhibits wide inter-individual differences in activity. In order to characterize sources of variability in CYP1A2 activity, we phenotyped (with the caffeine test) 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 also administered a detailed lifestyle questionnaire, including a quantitative food frequency questionnaire, and were assessed for plasma levels of carotenoids, tocopherols, retinol, ascorbic acid, cholesterol and triglycerides. In a stepwise multiple regression, 27% of the overall variation in CYP1A2 activity was explained by seven variables. Plasma lutein explained the largest portion of the variance (7%) and was negatively associated with CYP1A2 activity (p < 0.01), as were use of menopausal replacement estrogens (p = 0.04), plasma alpha-tocopherol (p = 0.05) and alcohol consumption (p = < 0.01). Acetaminophen use (p = 0.05), coffee consumption (p = 0.05) and plasma lycopene (p = 0.06) were positively associated with CYP1A2 activity. After adjustment for these variables, no association was found between CYP1A2 activity and sex, race, age, education, smoking, physical activity, weight, vitamin E supplements, the other plasma micronutrients measured, and dietary intakes of red meat, processed meat and cruciferous vegetables. Results were similar for colorectal cancer cases and controls. Almost two-thirds (73%) of the variability in CYP1A2 activity remained unexplained. This study confirms an enhancing effect of acetaminophen and coffee on CYP1A2 activity and suggests and inhibitory effect of estrogens, alcohol and food sources of lutein and alpha-tocopherol on this enzyme.

Adult↗
PubMed1996

Family history and risk of colorectal cancer in the multiethnic population of Hawaii.

Increased risk of colorectal cancer in individuals with family history of the disease has been observed consistently in past studies. However, limited attention has been given to the influence of ethnicity, the characteristics of the proband's tumor, and kinship. A population-based case-control study was conducted between 1987 and 1991 in Hawaii among 1,192 incident colorectal cancer cases and 1,192 sex-, age-, and ethnicity-matched population controls. The study identified 7,673 relatives for the cases and 7,823 relatives for the controls. With an estimating equation-based regression method, relatives of cases were found to have a 2.5-fold increased risk of colorectal cancer compared with relatives of controls (95% confidence interval (CI) 1.8-3.4) after adjustment for covariates. This increase in risk was greater for Japanese (odds ratio (OR) = 3.0, 95% CI 1.7-5.4) than Caucasians (OR = 1.8, 95% CI 1.2-2.9), for siblings (OR = 3.1, 95% CI 2.1-4.6) than parents (OR = 2.0, 95% CI 1.1-3.1), and when the index patient was diagnosed before the age of 55 years (OR = 4.1, 95% CI 2.1-8.0) with multiple tumors (OR = 9.5, 95% CI 4.4-20.6), with a distant stage (OR = 4.6, 95% CI 2.7-7.8), or with cancer of the right colon (OR = 3.0, 95% CI 2.0-4.4) or the rectum (OR = 3.0, 95% CI 1.8-4.8). The increase in risk was not affected by the relative's sex. Relatives of cases were not at increased risk for other common cancers. It is estimated that approximately 11.1% and 6.5% of colorectal cancers are attributable to a first degree family history of the disease for Japanese and Caucasians, respectively. These data and those of previous studies strongly suggest that individuals with a family history of colorectal cancer in a first degree relative are at increased risk for the disease and should receive regular diagnostic screening. Characteristics of the index case, such as age and stage at diagnosis, subsite and number of tumors, and race, as well as kinship, may be important in assessing the colorectal cancer risk of a relative.

Aged↗
PubMed1996

Predictors of N-acetyltransferase activity: should caffeine phenotyping and NAT2 genotyping be used interchangeably in epidemiological studies?

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.

Acetylation↗
PubMed1995

An ecological study of diet and lung cancer in the South Pacific.

Incidence rates of lung cancer have been markedly lower for Fiji than for other South Pacific countries, despite similar rates of smoking. We conducted population-based surveys in several island nations of the South Pacific (Cook Islands, Fiji, Tahiti and New Caledonia) and used data from Caucasian, Japanese, Hawaiian, Filipino and Chinese controls in a case-control study of lung cancer in Hawaii to investigate the role of diet in explaining differences in lung cancer incidence among 20 ethnic-sex groups. In a stepwise linear regression of lung cancer rates on smoking, diet and other variables, smoking, as expected, explained the majority (61%) of the variability in incidence. However, several dietary components also explained significant portions of the variance. Lutein intake explained 14% and vitamin E intake, cholesterol intake and height explained 5-7% each of the remaining variance in incidence. Associations with lutein and vitamin E were inverse, whereas those with cholesterol and height were direct. Dietary beta-carotene intake was not associated with lung cancer incidence. These ecological data provide evidence for a protective effect of lutein against lung cancer. A protective effect of dietary vitamin E and a risk-enhancing effect of dietary cholesterol are also suggested.

Adolescent↗