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Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.

ABSTRACT: A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accumulating clinical evidence about ethnic differences in the frequencies of polymorphisms within many of the important cancer drug-related genes. This article reviews the current clinical evidence for ethnic differences in anticancer drug disposition and sensitivity while highlighting the challenges, and potential solutions, to acquiring such knowledge. The discovery of "ethnic-specific genetic signatures," representing unique sets of drug susceptibility-governing polymorphisms, may be the outcome of such work. Ultimately, such understanding will further the lofty goal of individualization of chemotherapy based on a person's unique genetic make-up to improve the tolerability and effectiveness of chemotherapy for all patients.

SUBMITTER: O'Donnell PH

PROVIDER: S-EPMC2774468 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.

O'Donnell Peter H PH Dolan M Eileen ME

Clinical cancer research : an official journal of the American Association for Cancer Research 20090721 15

A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accu ...[more]

PMID: 19622575

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Project description:BackgroundOur objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form.MethodsAll 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced.Results(i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism.ConclusionsFacial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.

Project description:ObjectiveTo determine the extent to which socioeconomic and racial/ethnic differences in cancer screening discussion between a patient and his/her primary care physician are due to "within-physician" differences (the fact that patients were treated differently by the same physicians) versus "between-physician" differences (that they were treated by a different group of physicians).Data sourcesWe use data from the baseline patient and physician surveys of two community trials from the Communication in Medical Care (CMC) research series. The two studies combined provide an analysis sample of 5,978 patients ages 50-80 nested within 191 primary care physicians who practiced throughout Southern California.Study designOur main outcomes of interest are whether the physician has ever talked to the patient about fecal occult blood test (FOBT; for colorectal cancer screening), mammogram (for breast cancer screening, female patients only) and the prostate-specific antigen test (PSA, male patients only). We consider five racial/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic, Asian, and other race/ethnicity. We measure socioeconomic status by both income and education. For each type of cancer screening discussion, we first estimate a probit model that includes patient characteristics as the only covariates to assess the overall differences. We then add physician fixed effects to derive estimates of "within-" versus "between-" physician differences.Principal findingsThere was a strong education gradient in the discussion of all three types of cancer screening and most of the education differences arose within physicians. Disparities by income were less consistent across different screening methods, but seemed to have arisen mainly because of "between-physician" differences. Asians were much less likely, compared with whites, to have received discussion about FOBT and PSA and these differences were mainly "within-physician" differences. Black female patients, however, were much more likely, compared with whites treated by the same physicians, to have discussed mammogram with their physicians.ConclusionsDifferences in cancer screening discussion along the different dimensions of patient SES may have arisen because of very different mechanisms and therefore call for a combination of interventions. Physicians need to be aware of the persistent disparities by patient education in clinical communication regarding cancer screening and tailor their efforts to the needs of low-education patients. Quality-improvement efforts targeted at physicians practicing in low-income communities may also be effective in addressing disparities in cancer screening communication by patient income.

Dataset Information

Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.

Publications

Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.

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