Search PubMed⌕ Search

Biomedical subjects

Daniel O Stram

Publications and source records attributed to Daniel O Stram.

At least 37 records · Page 2Linked to original sources
PubMed2005

Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysis.

BACKGROUND: The PROGINS allele of the progesterone receptor (PGR) gene has been associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. We set out to refine the association between common variation at the PGR gene locus and these two diseases. METHODS: We characterized the haplotype structure of the PGR gene by genotyping 54 single-nucleotide polymorphisms (SNPs) in 349 women. We then selected a subset of 17 haplotype-tagging SNPs that captured variation across the locus and typed them in 267 ovarian cancer case patients and 397 control subjects from two case-control studies and in 1715 breast cancer case patients and 2505 control subjects from a cohort study. RESULTS: The PGR locus was characterized by four blocks of strong linkage disequilibrium. Two SNPs in block 4 were associated with an increased risk of ovarian cancer among homozygous carriers as compared with noncarriers: rs1042838 (PROGINS allele; odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.19 to 8.75, P = .022) and rs608995 (minor allele; OR = 3.10, 95% CI = 1.63 to 5.89, P<.001). The PROGINS allele was observed on a subset of chromosomes carrying the minor allele at rs608995, and its association with ovarian cancer was fully explained by its association with rs608995. In addition, rs608995 fell on two common haplotypes (4-D and 4-E), whose association with ovarian cancer was the same as that of rs608995. These same two haplotypes were associated with a non-statistically significantly reduced risk of breast cancer. CONCLUSIONS: Variation in PGR was associated with ovarian cancer risk, although the strongest result was not with the PROGINS allele. Instead, any causal allele(s) are likely in or downstream of block 4 and carried on haplotypes 4-D and 4-E. There was some evidence that the same variation was associated with a reduced risk of breast cancer, but the association was not statistically significant.

Adult↗
PubMed2005

Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index.

BACKGROUND: According to the International Neuroblastoma Pathology Classification, neuroblastomas exhibiting MYCN amplification (A-MYCN) have unique histologic features-namely, undifferentiated/poorly differentiated subtype with a high mitosis-karyorrhexis index (U/PD-H). Nonetheless, certain tumors possessing these histologic characteristics contain a nonamplified MYCN gene (NA-MYCN). METHODS: The clinical characteristics of patients from the Children's Cancer Group (CCG) 3881 and 3891 studies who had neuroblastoma, U/PD-H, exhibiting A-MYCN (n=68) or NA-MYCN (n=33) were investigated. The histologic and cytologic features of tumors (A-MYCN, n=62; NA-MYCN, n=28) filed at the Pathology Reference Laboratory, Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, were reviewed, and nucleolar areas in undifferentiated neuroblastic cells were evaluated using image analysis methods. RESULTS: All 68 patients whose tumors exhibited A-MYCN had disease that was in an advanced clinical stage (Stage III or IV); 89.7% of these patients were diagnosed between ages 0.5 and 3.5 years, and 67 of the 68 had been treated with the high-risk protocol in the CCG-3891 study. Children whose tumors exhibited NA-MYCN were evenly distributed across all age groups; 30 of these 33 children had advanced-stage disease, and 26 had been treated with a high-risk protocol. The prognosis associated with A-MYCN (event free survival [EFS], 15.7%; overall survival [OS], 22.2%) was significantly poorer than the prognosis associated with NA-MYCN (EFS, 56.1%; OS, 69.3%). The lone histologic/cytologic difference between tumors exhibiting A-MYCN and tumors exhibiting NA-MYCN involved nucleolar appearance. Neuroblastic cells in tumors exhibiting A-MYCN were characterized by the presence of 1 or more large, prominent nucleoli, and the mean nucleolar area was significantly greater in the 18 tumors exhibiting A-MYCN that were assessed (7.63 microm2) than in the 16 tumors exhibiting NA-MYCN that were assessed (5.53 microm2; P=0.004). CONCLUSIONS: Neuroblastomas, U/PD-H, were found to vary in terms of molecular background and clinical behavior. The results of the current study indicate that nucleolar enlargement in neuroblastic cells may be a sign of MYCN amplification.

Biomarkers, Tumor↗
PubMed2005

A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women.

BACKGROUND: Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia, perhaps because of lower endogenous estrogens. OBJECTIVE: The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents. DESIGN: Fifty-seven postmenopausal women participated in a randomized, controlled, dietary intervention study. The subjects consumed a very-low-fat diet (VLFD; 11% of energy as fat), a Step I diet (25% of energy as fat) supplemented with soy food (SFD; 50 mg isoflavones/d), or a control Step I diet (CD; 27% of energy as fat) with no soy food. All diets were prepared at the General Clinical Research Center of the University of Southern California. Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention. RESULTS: There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group. Serum insulin decreased significantly in the SFD group, and leptin decreased significantly in the SFD and VLFD groups; however, these changes did not differ significantly from the changes in the CD group. CONCLUSIONS: This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women. However, short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations.

Dietary Fats↗
PubMed2005

Comparison of prostate-specific antigen and hormone levels among men in Singapore and the United States.

Prostate cancer incidence rates markedly vary between countries. The highest rates of prostate cancer are observed in Western countries such as the United States, whereas the lowest rates are seen in Asian countries such as Singapore. To gain an understanding of the difference in prostate cancer burden between low-risk and high-risk populations, we examined serum prostate-specific antigen (PSA) levels among Singapore-Chinese men (n = 315) from the Singapore Chinese Health Study and African-American (n = 440), U.S. White (n = 355), U.S. Latino (n = 523), and Japanese-American (n = 349) men from the Hawaii-Los Angeles Multiethnic Cohort Study. All men had no history of prostate cancer at the time of blood draw. PSA measurements were assayed by one centralized diagnostic facility. Testosterone and 3alpha-androstanediol glucuronide levels were examined in a subsample of men. Scheffe's multiple comparison tests were used to evaluate differences in PSA and hormone levels between groups. PSA levels among the Singapore-Chinese (geometric mean = 1.43 ng/mL) were similar to that of African-Americans (1.46 ng/mL), U.S. Whites (1.28 ng/mL), and Japanese-Americans (1.22 ng/mL) and significantly higher than U.S. Latinos (1.18 ng/mL; P = 0.038). Although there was a strong correlation (R2= 0.89) between PSA levels and U.S. ethnic group-specific prostate cancer incidence rates before PSA screening (1983-1987), the levels among the Singapore-Chinese completely failed to relate to their low incidence rate. Testosterone and 3alpha-androstanediol glucuronide levels did not reflect racial/ethnic patterns of disease. Our results highlight a potentially large group of Singapore-Chinese men with undiagnosed prostate cancer. Given that the overall mortality rate of prostate cancer in Singapore is low, these undiagnosed cancers may be of nonaggressive type. Alternatively, PSA may be a poor marker of prostate cancer in this low-risk population.

Age Distribution↗
PubMed2005

Software for tag single nucleotide polymorphism selection.

This paper reviews the theoretical basis for single nucleotide polymorphism (SNP) tagging and considers the use of current software made freely available for this task. A distinction between haplotype block-based and non-block-based approaches yields two classes of procedures. Analysis of two different sets of SNP genotype data from the HapMap is used to judge the practical aspects of using each of the programs considered, as well as to make some general observations about the performance of the programs in finding optimal sets of tagging SNPs. Pairwise R2 methods, while the simplest of those considered, do tend to pick more tagging SNPs than are strictly needed to predict unmeasured (non-tagging) SNPs, since a combination of two or more tagging SNPs can form a prediction of SNPs that have no direct (pairwise) surrogate. Block-based methods that exploit the linkage disequilibrium structure within haplotype blocks exploit this sort of redundancy, but run a risk of over-fitting if used without some care. A compromise approach which eliminates the need first to analyse block structure, but which still exploits simple relationships between SNPs, appears promising.

Chromosome Mapping↗
PubMed2004

Common variation in BRCA2 and breast cancer risk: a haplotype-based analysis in the Multiethnic Cohort.

It is well established that rare mutations in BRCA2 predispose to familial breast cancer, but whether common variants at this locus contribute more modest risk to sporadic breast cancer has not been thoroughly investigated. We performed a haplotype-based study of BRCA2 among women in the Multiethnic Cohort Study (MEC), genotyping 50 SNPs spanning 109.4 kb of the BRCA2 gene. Twenty-one haplotype-tagging SNPs (including seven missense SNPs) were selected to predict the common BRCA2 haplotypes and were genotyped in a breast cancer case-control study nested in the MEC (cases, n=1715; controls, n=2502). Compared to non-carriers, we observed nominally significant positive associations for homozygous carriers of specific haplotypes in blocks 2 (haplotype 2c: OR=1.50; 95% CI, 1.08-2.09) and 3 (haplotype 3d: OR=1.50; 95% CI, 1.01-2.24). These results could be explained on the basis of a single marker in intron 24 (SNP 42: rs206340) that was correlated with these haplotypes and the homozygous state was associated with a significantly increased risk of breast cancer (AA versus GG genotypes: OR=1.59, 95% CI, 1.18-2.16; nominal P=0.005). This association was modestly stronger among women with advanced disease (OR=2.00, 95% CI, 1.30-3.08; P=0.002). In this exploratory analysis, we found little indication that common variation in BRCA2 dramatically impacts sporadic breast cancer risk. However, a significant elevation in risk was observed among approximately 6% of women who carried a specific haplotype pattern and may harbor a susceptibility allele at the BRCA2 locus.

Aged↗
PubMed2004

Tag SNP selection for association studies.

This report describes current methods for selection of informative single nucleotide polymorphisms (SNPs) using data from a dense network of SNPs that have been genotyped in a relatively small panel of subjects. We discuss the following issues: (1) Optimal selection of SNPs based upon maximizing either the predictability of unmeasured SNPs or the predictability of SNP haplotypes as selection criteria. (2) The dependence of the performance of tag SNP selection methods upon the density of SNP markers genotyped for the purpose of haplotype discovery and tag SNP selection. (3) The likely power of case-control studies to detect the influence upon disease risk of common disease-causing variants in candidate genes in a haplotype-based analysis. We propose a quasi-empirical approach towards evaluating the power of large studies with this calculation based upon the SNP genotype and haplotype frequencies estimated in a haplotype discovery panel. In this calculation, each common SNP in turn is treated as a potential unmeasured causal variant and subjected to a correlation analysis using the remaining SNPs. We use a small portion of the HapMap ENCODE data (488 common SNPs genotyped over approximately a 500 kb region of chromosome 2) as an illustrative example of this approach towards power evaluation.

Chromosome Mapping↗
PubMed2003

Revision of the International Neuroblastoma Pathology Classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular.

BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) comprises one of the categories of peripheral neuroblastic tumors. All tumors in this category, according to the original International Neuroblastoma Pathology Classification, are classified into an unfavorable histology group. Subsequently, it has been reported that GNBn can be divided into two prognostic subsets, a favorable subset (FS) and an unfavorable subset (US). METHODS: Histology slides from 70 patients who were enrolled in Children's Cancer Group studies 3881 and 3891 and who had a diagnosis of GNBn were reviewed jointly by the members of International Neuroblastoma Pathology Committee (INPC): 1) to confirm the diagnosis of GNBn, 2) to identify the FS and US by applying the same age-linked criteria that were used to distinguish the favorable histology group and unfavorable histology group in conventional neuroblastoma tumors from the neuroblastomatous component of GNBn tumors, and 3) to verify the significant prognostic difference between these two subsets. The patients had been used in a previous study, and survival data for the patients were updated since the time of their last report. RESULTS: The review clarified and illustrated morphologic characteristics of classical GNBn and it variants. The diagnosis of GNBn was confirmed in 67 of 70 patients. There were 22 patients with GNBn in the FS and 45 patients with GNBn in the US. The estimated survival differences between the FS and US patients with GNBn were statistically significant (8-year event free survival rate: 86.1% vs. 32.2%; P = 0.0003; overall survival rate: 90.5% vs. 33.2%; P = 0.0003). CONCLUSIONS: This study confirmed the recently defined prognostic subsets of GNBn. The INPC proposes to modify the International Neuroblastoma Pathology Classification by distinguishing the FS and the US among patients with GNBn tumors.

Child↗
PubMed2003

A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort.

The CYP19 gene encodes for aromatase (P450arom), a key steroidogenic enzyme that catalyzes the final step of estrogen biosynthesis. Apart from rare mutations in CYP19 which result in severe phenotypes associated with estrogen insufficiency, little is known about whether common variation in CYP19 is associated with risk of hormone-related diseases. In this study, we employed a haplotype-based approach to search for common disease-associated variants in this candidate breast cancer susceptibility gene among African-American, Hawaiian, Japanese, Latina and White women in the Multiethnic Cohort Study (MEC). We utilized 74 densely spaced single-nucleotide polymorphisms (SNPs) (one every approximately 2.6 kb) spanning 189.4 kb of the CYP19 locus to characterize linkage disequilibrium (LD) and haplotype patterns among 69-70 individuals from each ethnic population. We detected four regions of strong LD (blocks 1-4) that were quite closely conserved across populations. Within each block there was a limited diversity of common haplotypes (5 to 10 with a frequency >/=5%) and most haplotypes were observed to be shared across populations. Twenty-five haplotype-tagging SNPs (htSNPs) were selected to predict the common haplotypes with high probability (average Rh2=0.92) and genotyped in a breast cancer case-control study in the MEC (cases, n=1355; controls, n=2580). We first performed global tests for differences in risk according to the common haplotypes and observed significant haplotype-effects in block 2 [P=0.01; haplotypes 2b (OR=1.23; 95% CI, 1.07-1.40), 2d (OR=1.28; 95% CI, 1.01-1.62)]. We also found a common long-range haplotype comprised of block-specific haplotypes 2b and 3c to be associated with increased risk of breast cancer (haplotype 2b-3c: OR=1.31; 95% CI, 1.11-1.54). Our findings suggest the hypothesis that women with the long-range CYP19 haplotype 2b-3c may be carriers of a predisposing breast cancer susceptibility allele.

Adult↗
PubMed2003

Impact of radiotherapy for high-risk neuroblastoma: a Children's Cancer Group study.

PURPOSE: To assess the effect of local radiation administered to primary disease sites in children with high-risk neuroblastoma. MATERIALS AND METHODS: A total of 539 eligible patients were entered on protocol CCG-3891, consisting of chemotherapy, primary surgery, and 10 Gy of external beam radiation therapy (EBRT) to gross residual disease, followed by randomized assignment to continuation chemotherapy (CC) or autologous bone marrow transplantation (ABMT). ABMT patients received total body irradiation (TBI). RESULTS: Estimated event-free survival and overall survival at 5 years were 25% +/- 2% and 35% +/- 2%, respectively. Estimated 5-year locoregional recurrence rates were 51% +/- 5% and 33% +/- 7% for CC and ABMT patients (p = 0.004). For patients who received 10 Gy of EBRT to the primary, the addition of 10 Gy of TBI and ABMT decreased local recurrence compared with CC (22% +/- 12% and 52% +/- 8%, p = 0.022). EBRT did not increase acute toxicity, except for increased total parenteral nutrition administration. CONCLUSIONS: In combination with EBRT to the primary tumor site, the addition of 10 Gy of TBI as a component of high-dose chemotherapy with ABMT improved local control compared with CC without TBI. Results suggest a dose-response relationship for local EBRT. Short-term toxicity of local EBRT is limited.

Adolescent↗
PubMed2003

Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study.

We describe an approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes. Based on a preliminary sample of 70 control subjects chosen at random from each of the 5 ethnic groups in the MEC we estimate haplotype frequencies using a variant of the Excoffier-Slatkin E-M algorithm after genotyping a high density of SNPs selected every 3-5 kb in and surrounding a candidate gene. In order to evaluate the performance of a candidate set of htSNPS (which will be genotyped in the much larger case-control sample) we treat the haplotype frequencies estimate above as known, and carry out a formal calculation of the uncertainty of the number of copies of common haplotypes carried by an individual, summarizing this calculation as a coefficient of determination, R2h. A candidate set of htSNPS of a given size is chosen so as to maximize the minimum value of R2h over the common haplotypes, h.

Aromatase↗
PubMed2003

Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the Rh2 criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well.

Algorithms↗
PubMed2003

Bayesian spatial modeling of haplotype associations.

We review methods for relating the risk of disease to a collection of single nucleotide polymorphisms (SNPs) within a small region. Association studies using case-control designs with unrelated individuals could be used either to test for a direct effect of a candidate gene and characterize the responsible variant(s), or to fine map an unknown gene by exploiting the pattern of linkage disequilibrium (LD). We consider a flexible class of logistic penetrance models based on haplotypes and compare them with an alternative formulation based on unphased multilocus genotypes. The likelihood for haplotype-based models requires summation over all possible haplotype assignments consistent with the observed genotype data, and can be fitted using either Expectation-Maximization (E-M) or Markov chain Monte Carlo (MCMC) methods. Subtleties involving ascertainment correction for case-control studies are discussed. There has been great interest in methods for LD mapping based on the coalescent or ancestral recombination graphs as well as methods based on haplotype sharing, both of which we review briefly. Because of their computational complexity, we propose some alternative empirical modeling approaches using techniques borrowed from the Bayesian spatial statistics literature. Here, space is interpreted in terms of a distance metric describing the similarity of any pair of haplotypes to each other, and hence their presumed common ancestry. Specifically, we discuss the conditional autoregressive model and two spatial clustering models: Potts and Voronoi. We conclude with a discussion of the implications of these methods for modeling cryptic relatedness, haplotype blocks, and haplotype tagging SNPs, and suggest a Bayesian framework for the HapMap project.

Algorithms↗
PubMed2003

Correlation of dietary intake and colorectal cancer incidence among Mexican-American migrants: the multiethnic cohort study.

Studies of migrants, along with geographic and temporal variations in incidence, indicate that colorectal cancer is especially sensitive to changes in environmental factors, including, most importantly, diet. The goal of this research was to examine the changes in dietary practices that may be consistent with the changing incidence of colorectal cancer in the Los Angeles Mexican-American population. Cancer incidence and dietary intake data were available for over 35,000 Latinos of Mexican national origin currently participating in the prospective Multiethnic Cohort Study, representing the largest sample of Mexican-origin Latinos of any such study in the United States. The dataset is unique in that changes in cancer rates and in dietary behaviors across three generations could be examined. Most of the change in colorectal cancer rates occurred between the first and second generations, and, correspondingly, nearly all the dietary change also occurred between the first and second generations. Although some food traditions were retained by Mexican Americans, the dietary changes due to acculturation were significant and support an association between colorectal cancer risk and certain dietary components, notably, alcohol as a risk factor and nonstarch polysaccharides and vegetables as protective factors.

Acculturation↗
PubMed2003

Power and uncertainty analysis of epidemiological studies of radiation-related disease risk in which dose estimates are based on a complex dosimetry system: some observations.

This paper discusses practical effects of dosimetry error relevant to the design and analysis of an epidemiological study of disease risk and exposure. It focuses on shared error in radiation dose estimates for such studies as the Hanford Thyroid Disease Study or the Utah Thyroid Cohort Study, which use complex dosimetry systems that produce multiple replications of possible dose for the cohort. We argue that a simple estimation of shared multiplicative error components through direct examination of the replications of dose for each person provides information useful for estimating the power of a study to detect a radiation effect and illustrate this with an example based on the doses used for the Hanford Thyroid Disease Study. Uncertainty analysis (construction of confidence intervals) can be approached in the same way in simple cases. We also offer some suggestions for Monte Carlo-based confidence intervals.

Computer Simulation↗
PubMed2003

Dietary cryptoxanthin and reduced risk of lung cancer: the Singapore Chinese Health Study.

High prediagnostic serum beta-cryptoxanthin levels have been found to be associated with reduced risk of lung cancer in a recent cohort study of Chinese men in Shanghai, China. Data on dietary beta-cryptoxanthin, and other specific carotenoids and antioxidants in relation to lung cancer, particularly in non-Western populations, are scarce. The aim of the present study was to assess the roles of dietary antioxidants in the development of lung cancer. Between April 1993 and December 1998, 63,257 Chinese men and women ages 45-74 years in Singapore participated in a prospective study of diet and cancer. At baseline, an in-person interview was conducted using a structured questionnaire for information on usual dietary habits, tobacco smoking, and other lifestyle factors. A Singapore food composition database was used to estimate intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, vitamins A, C, and E, and folate in study subjects. During the first 8 years of follow-up, 482 lung cancer cases occurred among cohort members. High levels of dietary beta-cryptoxanthin were associated with reduced risk of lung cancer; relative to the lowest quintile, the self-reported smoking adjusted relative risks (95% confidence intervals) for the highest quintile were 0.73 (0.54-0.98) among all of the subjects and 0.63 (0.41-0.99) among current smokers. Before adjustment for cigarette smoking, dietary vitamin C was associated with a statistically significant reduction in risk of lung cancer. However the inverse vitamin C-lung cancer association was largely explained by smoking and dietary beta-cryptoxanthin. Other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin), vitamins A and E, and folate were not associated significantly with lung cancer risk after adjustment for cigarette smoking. We recognized that potential measurement errors in cigarette smoking may exert an effect on the dietary beta-cryptoxanthin-lung cancer association. After additional adjustments were made for the residual confounding by smoking using statistical models, about 15-40% reduction in risk of lung cancer was seen for subjects in the highest versus lowest 10th percentile of dietary beta-cryptoxanthin. The present study lends additional credence to prior experimental and epidemiological data in support of the hypothesis that dietary beta-cryptoxanthin is a chemopreventive agent for lung cancer in humans.

Aged↗