W. Douglas Thompson

Autosomal dominant inheritance of early‐onset breast cancer. Implications for risk prediction

Background. Improvements in screening techniques have made significant contributions to the early detection of breast cancer. Physicians thus face the task of providing appropriate screening schedules for their patients. One group for whom this is particularly important are those women with a family history of breast cancer.

The genetic attributable risk of breast and ovarian cancer

The age‐specific proportion of breast and ovarian cancer in the general population that is likely to be due to a breast/ovarian cancer susceptibility gene(s) is estimated. In addition, the age‐specific penetrance of ovarian cancer for women predicted to be carriers of a susceptibility gene is calculated using population‐based data.

A rEAPPRAISAL OF THE KAPPA COEFFICIENT

Kappa is frequently used in epidemiology as an index of the quality of measurement for binary characteristics. The authors discuss the strong dependence of kappa on true prevalence, and they examine the relationship of the value of kappa to the degree of attenuation of the odds ratio that results from non-differential misclassification. It is concluded that under certain circumstances kappa can be interpreted as an indicator of validity, i.e. unbiasedness of the odds ratio, rather than simply as one of reliability. Cautions are stressed regarding (1) possible variation in the quality of measurement and (2) possible lack of independence of errors for the paired measurements from which kappa is calculated. An important implication for the design of reliability studies is that they should be conducted in populations where the distribution of the factor of interest is similar to that for the settings in which the measurement technique will ultimately be applied.

Silver nanospheres are cytotoxic and genotoxic to fish cells

Nanoparticles are being widely investigated for a range of applications due to their unique physical properties. For example, silver nanoparticles are used in commercial products for their antibacterial and antifungal properties. Some of these products are likely to result in silver nanoparticles reaching the aquatic environment. As such, nanoparticles pose a health concern for humans and aquatic species. We used a medaka (Oryzias latipes) cell line to investigate the cytotoxicity and genotoxicity of 30nm diameter silver nanospheres. Treatments of 0.05, 0.3, 0.5, 3 and 5microg/cm(2) induced 80, 45.7, 24.3, 1 and 0.1% survival, respectively, in a colony forming assay. Silver nanoparticles also induced chromosomal aberrations and aneuploidy. Treatments of 0, 0.05, 0.1 and 0.3microg/cm(2) induced damage in 8, 10.8, 16 and 15.8% of metaphases and 10.8, 15.6, 24 and 24 total aberrations in 100 metaphases, respectively. These data show that silver nanoparticles are cytotoxic and genotoxic to fish cells.

The calculation of breast cancer risk for women with a first degree family history of ovarian cancer

SummaryRecent linkage analyses demonstrate the strength of the genetic association between breast and ovarian cancer in some families. These findings highlight the importance of considering a womans family history of ovarian cancer in the calculation of her risk of breast cancer. In this study, data on breast and ovarian cancer from the Cancer and Steroid Hormone Study, a large, population-based, case-control study conducted by the Centers for Disease Control, are used to calculate age-specific and cumulative risks of developing breast cancer for a woman with a first degree family history of ovarian cancer. These risks are calculated using maximum likelihood estimates from an autosomal dominant genetic model fit previously to the observed age-specific recurrence data of breast cancer among first degree relatives of the breast cancer cases and controls in these data as well as from genotype-specific estimates of lifetime ovarian cancer risk derived from this model. Under this model, the lifetime risk of developing breast cancer for a woman with one or two first degree relatives affected with ovarian cancer is estimated to be approximately 13% and 31%, respectively. A woman with one first degree relative affected with ovarian cancer and one first degree relative affected with breast cancer has an estimated risk of 40 percent of developing breast cancer by age 79 years if the relative with breast cancer was diagnosed in her thirties. This risk decreases with increasing age of onset of the relative affected with breast cancer.

Comparison of the family history method to direct interview factors affecting the diagnosis of depression

This study compares information on the diagnosis of depression obtained by family history reports with the formation obtained by direct interview. Reports were obtained from family members on the psychiatric status of 696 individuals for whom direct SADS-L interviews were also available. The effects on family history reports of subjects characteristics, treatment status, age of onset of depression, and endogenous symptoms were examined. Sensitivity and specificity for family history reports on the specific symptoms of depression are also reported. The specificity of family history reports for the diagnosis of depression was consistently high but sensitivity varied as a function of subject and illness characteristics. Sensitivity was somewhat higher for females than males and appreciably higher for probands than for their first-degree relatives and spouses. Sensitivity was increased whenever treatment, hospitalization or endogenous symptoms were present in the subject, indicating that family history reports are most accurate for detecting the severest cases of depression. Finally, the symptoms of depression that are least accurately reported by relatives are identified and suggestions for modifying the family history criteria for depression are proposed.

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.

Study design: Evaluating gene–environment interactions in the etiology of breast cancer – the WECARE study

IntroductionDeficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated.DesignTo examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses.ConclusionsOur study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions.

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Pagets disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.

Relationship between breast histopathology and family history of breast cancer

Background. The relationship between breast cancer histology and a number of epidemiologic risk factors associated with breast cancer was examined in 4071 histologically confirmed breast cancer cases aged 20 to 54 years from the Cancer and Steroid Hormone Study.