Biomedical subjects

B E Henderson

Publications and source records attributed to B E Henderson.

At least 19 recordsLinked to original sources

PubMed2005

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

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.

Breast Neoplasms↗

PubMed2003

A Y chromosomal influence on prostate cancer risk: the multi-ethnic cohort study.

BACKGROUND: A Y chromosomal role in prostate cancer has previously been suggested by both cytogenetic findings and patterns of Y chromosomal gene expression. We took advantage of the well established and stable phylogeny of the non-recombining segment of the Y chromosome to investigate the association between Y chromosomal DNA variation and prostate cancer risk. METHODS: We examined the distribution of 116 Y lineages in 930 prostate cancer cases and 1208 controls from four ethnic groups from a cohort study in Hawaii and California. RESULTS: One lineage, found only among the Japanese group in our study, was associated with a statistically significant predisposition to prostate cancer (odds ratio (OR) = 1.63; 95% confidence interval (CI) 1.07 to 2.47), and, in particular, to high severity disease in younger individuals (OR = 3.89; 95% CI 1.34 to 11.31). CONCLUSIONS: This finding suggests that a Y chromosomal factor contributes significantly to the development of prostate cancer in Japanese men.

Aged↗

PubMed2001

Germ-line HER-2 variant and breast cancer risk by stage of disease.

HER-2 gene amplification and protein overexpression has been associated with increased risk of advanced-stage breast cancer and poor prognosis. Recently, a single missense point mutation (Ile(655)Val) in the transmembrane domain of the HER-2 gene was associated with a 40% increase in breast cancer risk among women 45 years of age and younger. In this analysis, we measured the association between the Ile(655)Val variant and postmenopausal breast cancer among women participating in the Hawaii and Los Angeles Multiethnic Cohort. Risk of localized breast cancer was significantly elevated among women with the HER-2 variant, but not among women with regional or metastatic disease. Women with at least one copy of the Valine variant were approximately one-half as likely to have high-stage as low-stage breast cancer (P =.02), and this effect was present across racial/ethnic groups.

Aged↗

PubMed2001

Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women?

Breast cancer risk is substantially lower in Singapore than in women from the United STATES: Part of the risk discrepancy is probably explained by differences in the production of endogenous estrogens, but differences in the pathway by which estrogen is metabolized may also play a role. We undertook a study to determine whether the ratio of urinary 2-hydroxyestrone (2OHE(1)):16alpha-hydroxyestrone (16alpha-OHE(1)) was higher in Singapore Chinese than in a group of United States (predominantly African-American) women living in Los ANGELES: We also wanted to determine whether any difference in estrogen metabolite ratio between these two groups of women was greater than that in estrone (E(1)), estradiol (E(2)) and estriol (E(3)). The participants in this study were randomly selected healthy, non-estrogen using women participating in the Singapore Chinese Health Study (n = 67) or the Hawaii/Los Angeles Multiethnic Cohort Study (n = 58). After adjusting for age and age at menopause, mean urinary 2-OHE(1) was only 23% (P = 0.03) higher in Singapore Chinese than in United States women, and there were no statistically significant differences in 16alpha-OHE(1) levels or in the ratio of 2-OHE(1):16alpha-OHE(1) between the two groups. The adjusted mean 2-OHE(1):16alpha-OHE(1) ratio was 1.63 in Singapore Chinese and 1.48 in United States women (P = 0.41). In contrast, the adjusted mean values of E1, E2, and E3 were 162% (P < 0.0001), 152% (P < 0.0001), and 92% (P = 0.0009) higher, respectively, in United States women than in Singapore Chinese women. Our study suggests that urinary E1, E2, and E3 reflect the differences in breast cancer risk between Singapore Chinese and United States women to a stronger degree than the estrogen metabolites 2OHE(1) and 16alpha-OHE(1) or the ratio of 2OHE(1):16alpha-OHE(1.)

Aged↗

PubMed2001

Risk of endometrial cancer and estrogen replacement therapy history by CYP17 genotype.

Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometrial cancer. We examined the association between endometrial cancer risk and estrogen replacement therapy (ERT) by CYP17 genotype using 51 incident cases and 391 randomly selected controls from a multiethnic cohort in Hawaii and Los Angeles, California. The relative risk of endometrial cancer was calculated for ever use versus never use of ERT by CYP17 genotype (TT, TC, and CC). We found that women who reported ever taking ERT were more than twice as likely to develop endometrial cancer as women who never took ERT [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.19-4.23]. Among these women, the risk of endometrial cancer was higher for women homozygous for the CYP17 T allele (OR, 4.10; 95% CI, 1.64-10.3), but not for women with the C allele (OR, 1.31; 95% CI, 0.53-3.21). These preliminary findings suggest that CYP17 or other variants in estrogen biosynthesis or metabolism pathways may be potential markers of endometrial cancer susceptibility due to ERT.

Aged↗

PubMed2001

Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates.

We conducted a nested case-control study to evaluate whether polymorphisms in two genes involved in estrogen metabolism, CYP17 and HSD17B1, were useful in developing a breast cancer risk model that could help discriminate women who are at higher risk of breast cancer. If polymorphisms in these genes affect the level of circulating estrogens, they may directly influence breast cancer risk. The base population for this study is a multiethnic cohort study that includes African-American, Non-Latina White, Japanese, Latina, and Native Hawaiian women. For this analysis, 1508 randomly selected controls and 850 incident breast cancer cases of the first four ethnic groups who agreed to provide a blood specimen were included (76 and 80% response rates, respectively). The CYP17 A2 allele and the HSD17B1 A allele were considered "high-risk" alleles. Subjects were then classified according to number of high-risk alleles. After adjusting for age, weight, and ethnicity, we found that carrying one or more high-risk alleles increases the risk of advanced breast cancer in a dose-response fashion. The risk among women carrying four high-risk alleles was 2.21 [95% confidence interval (CI), 0.98-5.00; P for trend = 0.03] compared with those who carried none. This risk was largely limited to women who were not taking hormone replacement therapy (relative risk, 2.60; 95% CI, 0.95-7.14) and was most pronounced among those weighing 170 pounds or less (RR, 3.05; 95% CI, 1.29-7.25). These findings suggest that breast cancer risk has a strong genetic component and supports the theory that the underlying mechanism of "complex traits" can be understood using a multigenic model of candidate genes.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Cancer mortality in relation to environmental chromium exposure.

From the 1950s to the 1980s, hexavalent chromium compounds were used as additives at certain water-cooling towers at three southern California gas compressor facilities. Claims of potential residential chromium exposure prompted the examination of age-adjusted mortality rates during 1989 to 1998 for lung cancer, all cancer, and all deaths for neighborhoods near versus distant from the plants. Differences in the rates between areas tended to be small and not statistically significant. The only significant difference was a lower, rather than higher, rate of total cancer among women in the potentially exposed areas. Study limitations preclude a definitive assessment of risk, but similar to previous investigations of cancer in relation to environmental chromium exposure in other locations, this study found no evidence of a cancer hazard among residents living near these California gas compressor facilities.

California↗

PubMed2001

Risk factors for cardiovascular and cerebrovascular death among African Americans and Hispanics in Los Angeles, California.

OBJECTIVE: To describe the risk factors associated with cardiovascular mortality in the African American (AA) and Hispanic populations in Los Angeles County in an effort to define causes for the excess mortality seen in AAs. METHODS: This was a longitudinal analysis of all-cause, cardiovascular, and cerebrovascular mortality in a large, prospective multiethnic cohort of individuals aged 45-74 years. Death rates between AA and Hispanic men and women during the six-year period from 1993 to 1998 due to hypertension, cardiomyopathy, acute myocardial infarction (AMI), ischemic heart disease, and stroke were compared. RESULTS: There were 1,157 deaths due to cardiovascular disease (CVD) or cerebrovascular disease among the 71,798 eligible members of the cohort included in these analyses. Age-adjusted mortality rates were two to five times higher in AAs as compared with Hispanics (e.g., 373.15 in AAs for hypertensive disease vs 50.37 in Hispanics). A history of hypertension was the most common significant risk factor for CVD; other risk factors significantly associated with CVD mortality included cigarette smoking and a past history of diabetes and stroke. Adjusting for these factors did not remove the significance of AA ethnicity as a risk factor for CVD mortality in either subjects reporting or subjects not reporting hypertension at baseline. CONCLUSIONS: The evidence for both higher relative severity and higher incidence of hypertensive disease among AAs, and the consistency of the effect across gender, suggests that a major determinant of risk may be a gene environment interaction.

Black or African American↗

PubMed2001

Genetic determinants of serum prostate-specific antigen levels in healthy men from a multiethnic cohort.

We recently reported an association between prostate cancer risk and polymorphisms in the prostate-specific antigen (PSA) and androgen receptor (AR) genes. The purpose of this study is to test whether these two polymorphisms, AR CAG and PSA ARE1, influence serum PSA levels in healthy men. Serum PSA and the two genotypes were assayed for 420 healthy men from a multiethnic cohort, and regression models were fit to estimate the effects of AR CAG genotype and PSA ARE1 genotype on serum PSA levels. Predicted serum PSA decreased 3.5% with each additional AR CAG repeat decile (P = 0.01). Serum PSA was also associated with PSA ARE1 genotype, with PSA levels higher among men with the PSA AA genotype compared with men with the AG or GG genotypes (P = 0.02). The relationship between serum PSA level and AR CAG length differed according to PSA genotype (P = 0.049): for genotype GG, the slope was not significantly different from zero (P = 0.74); for genotype AG, serum PSA increased 4.5% with each decrease of one CAG repeat decile (P = 0.03); for genotype AA, serum PSA increased 7% with each decrease of one CAG repeat decile (P = 0.02). These results indicate that in healthy men, genetic variants in the PSA and AR genes contribute to variation in serum PSA levels. Men with the PSA AA genotype and short AR CAG alleles have, on average, higher serum PSA levels.

Aged↗

PubMed2000

Future possibilities in the prevention of breast cancer: role of genetic variation in breast cancer prevention.

Risk factors for breast cancer are related to endogenous hormones and reproductive events. As such, traditional cancer prevention strategies are not easily applicable. Tamoxifen and other selective estrogen receptor modulators (SERMs) offer a new preventive strategy for some high-risk women, but have not yet been shown to be efficacious for all women. New tools to identify high-risk women are needed. One such tool is the development of a multigenic model of breast cancer susceptibility that can be used to screen women in order to identify those who carry a combination of alleles that puts them at significantly increased risk.

Adult↗

PubMed2000

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

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

Black or African American↗

PubMed2000

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

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

Black or African American↗

PubMed2000

Vitamin D receptor genotype and breast cancer in Latinas (United States).

OBJECTIVE: Polymorphism in the vitamin D receptor (VDR) gene has been associated with variation in bone mineral density and with prostate cancer risk. The purpose of this study was to determine whether polymorphism in the VDR gene may also influence breast cancer risk. METHODS: Polymorphisms in the 5' and 3' ends of the VDR gene were genotyped for 143 Latina women with breast cancer and 300 cohort controls. RESULTS: Both the BsmI and poly-A polymorphisms in the 3' end of the VDR gene were associated with breast cancer risk, with a trend for increasing risk with increasing number of BsmI B alleles or short (S) poly-A alleles. Compared to subjects having two long poly-A alleles (genotype LL), odds ratios (and 95% confidence intervals) were 1.5 (1.0 2.3) and 3.2 (1.5-6.9) for subjects having genotypes SL and SS, respectively. Compared to BsmI genotype bb, odds ratios (and 95% confidence intervals) were 1.6 (1.1-2.5) and 2.2 (1.0-4.7) for genotypes Bb and BB respectively. The start codon polymorphism, FokI, was not associated with breast cancer risk. CONCLUSION: These results suggest that polymorphic variation in or near the 3' end of the VDR gene influences breast cancer risk in Latina women.

Aged↗

PubMed2000

Ethnic differences in post-menopausal plasma oestrogen levels: high oestrone levels in Japanese-American women despite low weight.

Breast cancer incidence in Japanese-American women is approaching that of US Whites. We investigated whether this shift is paralleled by similar post-menopausal plasma hormone levels in the two ethnic groups. We also included African-American and Latina women to further our understanding of possible ethnic differences in oestrogen metabolism. We measured androstenedione (A), oestrone (E1) and oestradiol (E2) in 30 Japanese-American, 39 non-Latina White ('White'), 66 African-American and 58 Latina women. The (age-adjusted) geometric mean E1 levels were 34 pg ml(-1) in Japanese-Americans, 28 pg ml(-1) in Whites, 35 pg ml(-1) in African-Americans and 31 pg ml(-1) in Latinas. After adjustment for body mass index, Japanese-Americans had the highest mean E1 value of all groups and this was statistically significantly greater than the value for Whites (P(t-test) = 0.05). The geometric mean A concentrations were also highest in Japanese-Americans. There was little ethnic difference in E2 levels. In conclusion, post-menopausal plasma oestrogen levels in Japanese-American women are at least as high as those in Whites.

Aged↗

PubMed2000

Hormonal carcinogenesis.

Hormone-related cancers, namely breast, endometrium, ovary, prostate, testis, thyroid and osteosarcoma, share a unique mechanism of carcinogenesis. Endogenous and exogenous hormones drive cell proliferation, and thus the opportunity for the accumulation of random genetic errors. The emergence of a malignant phenotype depends on a series of somatic mutations that occur during cell division, but the specific genes involved in progression of hormone-related cancers are currently unknown. In this review, the epidemiology of endometrial cancer and breast cancer are used to illustrate the paradigms of hormonal carcinogenesis. Then, new strategies for early detection and prevention of hormonal carcinogenesis are discussed. This includes developing polygenic models of cancer predisposition and the further development of safe and effective chemopreventives that block target sequence activity. We developed polygenic models for breast and prostate cancer after hypothesizing that functionally relevant sequence variants in genes involved in steroid hormone metabolism and transport would act together, and also interact with well-known hormonally related risk factors, to define a high-risk profile for cancer. A combination of genes each with minor variation in expressed activity could provide a degree of separation of risk that would be clinically useful as they could yield a large cumulative difference after several decades. The genes included in the breast cancer model are the 17beta-hydroxysteroid dehydrogenase 1 (HSD17B1) gene, the cytochrome P459c17alpha (CYP17) gene, the aromatase (CYP19) gene, and the estrogen receptor alpha (ER) gene. The prostate cancer model includes the androgen receptor gene (AR), steroid 5alpha-reductase type II (SRD5A2), CYP17 and the 3beta hydroxysteroid dehydrogenase (HSD3B2) gene. We present data from our multi-ethnic cohort to support these models.

Breast Neoplasms↗

PubMed2000

Elevated mortality rates from circulatory disease in African American men and women of Los Angeles County, California--a possible genetic susceptibility?

OBJECTIVE: Reports of higher mortality in African Americans have often focused on socioeconomic differences. Such differences do not explain the excess mortality in African Americans compared with Hispanics in Los Angeles County. We suggest the existence of genetic factors to explain at least some of the differences in mortality risk. METHODS: We compared the mortality rates from circulatory diseases in African American and Hispanic adults of Los Angeles County for 1988 to 1992 with the frequency of the angiotensin-converting enzyme (ACE) genotype. RESULTS: African American adults 45 to 74 years old had a 2-fold higher overall mortality rate than Hispanics. The largest differences were seen for hypertensive disease and cardiomyopathy in men; the most striking differences were seen in the youngest age group. Rates were lower in women than in men, but African American women also showed substantial excess compared with Hispanics. ACE genotype also showed a significant difference between the Hispanic and African American population; the latter had a significantly higher prevalence of the DD genotype, which is associated with a higher level of circulating enzyme, and lower prevalence of the II genotype, which is associated with a lower enzyme level. CONCLUSION: African American adults aged 45 to 74 years in Los Angeles County have a substantial excess mortality from hypertensive diseases compared with a similar Hispanic population. The frequency of the ACE DD genotype was higher in African Americans than in Hispanics. These studies may indirectly support the possibility of a genetic contribution to the excess hypertensive disease mortality in African Americans.

Aged↗

PubMed2000

A cohort mortality study among gas generator utility workers.

An earlier cohort study tracked the mortality experience through 1988 of male employees at five utility companies in the United States. Workers employed by the Pacific Gas and Electric Company (PG&E) were part of that study, but results for PG&E employees overall or for those involved in gas generator plant operations where hexavalent chromium compounds were used in open and closed systems from the 1950s to early 1980s were not reported. To evaluate risk of lung cancer and other diseases, a cohort of 51,899 PG&E male workers was followed for mortality from 1971 through 1997. Observed numbers of deaths were compared with those expected based on rates in the general California population, with standardized mortality ratios (SMR) and corresponding 95% confidence intervals (CI) calculated for the total cohort and for subsets defined by potential for gas generator plant exposure. A total of 10,591 deaths were observed, a number significantly less than expected (SMR, 0.89; 95% CI, 0.87 to 0.91). No significant excesses of total or specific cancers were observed, with SMR typically near or below 1.0. Lung cancer mortality in the entire cohort was close to expected (SMR, 0.98; 95% CI, 0.92 to 1.05), with no excess detected among persons who worked (SMR, 0.81; 95% CI, 0.35 to 1.60) or trained (SMR, 0.57; 95% CI, 0.12 to 1.67) at gas generator facilities. Furthermore, risk of lung cancer did not increase with increasing duration of employment or time since hire. The study thus provides no evidence that occupational exposures at PG&E facilities resulted in increased risk of lung cancer or any other cause of death. The results indicate that any chromium exposures were of insufficient magnitude to result in increased risk of lung cancer.

Adult↗

PubMed2000

Declining cancer rates in the 1990s.

PURPOSE: To provide evidence of a substantial decline in cancer rates for the period 1991 through 1995 and characterize major risk factors that seem to be driving secular trends in cancer mortality and incidence. DESIGN: Incidence and mortality rates were calculated using national surveillance data collected through the Surveillance, Epidemiology, and End Results (SEER) program and the National Center for Health Statistics. RESULTS: All-sites cancer incidence and mortality fell in the period 1991 through 1995; this decline is largely attributable to decreases in the smoking-related cancers, especially lung cancer. Of the 20 leading incident cancers today, both incidence and mortality are decreasing among 11 sites for men and 12 for women. In men, the decline in mortality has been notable and is especially apparent for the smoking-related cancers, including those of the lung, oral cavity and pharynx, larynx, and, to a lesser extent, bladder. In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Three cancers continued to show substantial increases in mortality through 1995 for both men and women (liver, multiple myeloma, and non-Hodgkin's lymphoma), while incidence rates continued to climb for liver cancer, non-Hodgkin's lymphoma, and melanoma. CONCLUSION: Data from the SEER program on recent trends in cancer incidence and mortality show that cancer rates are generally on the decline, largely because of reductions in smoking-related cancers. A consistent increase in mortality rates due to liver cancer poses a new health care challenge, one that will require the development of an effective treatment for individuals currently infected with hepatitis C or B to prevent mortality rates from continuing to increase.

Female↗