Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III?

BACKGROUND AND AIMS: To investigate if frequency of outdoor recreational activity (ORA) predicts cardiovascular disease (CVD) mortality, independent of serum 25(OH)D concentration. METHODS AND RESULTS: Baseline data on ORA and serum 25(OH)D, collected from 11,746 participants aged 30-90 years in the Third National Health and Nutrition Examination Survey during 1988-1994, were linked to the National Death Index for assessment of CVD deaths from baseline through December 2006. CVD mortality as a primary cause of death was assessed during a mean follow up of 12.9 (SD, 4.2) years. There were 1519 CVD deaths during follow up. A strong positive association was observed between frequency of ORA in the last month and serum 25(OH)D (p < 0.001). Compared to participants who did no ORA in the last month, the hazard ratio (HR) of CVD mortality was 0.72 (95% confidence interval 0.58-0.90) for those doing ORA 1-4 times, 0.64 (0.47-0.89) for 5-12 times, 0.70 (0.56-0.89) for 13-30 times and 0.63 (0.47-0.84) for ≥30 times (p-trend < 0.001), in a Cox proportional hazards regression model which included 25(OH)D and CVD risk factors. Serum 25(OH)D was inversely associated with CVD mortality (p-trend, 0.01) in this same model. CONCLUSIONS: An inverse association between ORA and CVD mortality was observed independent of 25(OH)D. The underlying mechanism for this association may not involve 25(OH)D hence, further studies are warranted to confirm and investigate the underlying mechanism.

Familial excess longevity in Utah genealogies.

We evaluated the influence of family history on longevity by examining longevity in a cohort of 78,994 individuals drawn from the Utah Population Database (UPDB) who were born between 1870 and 1907, and lived to at least age 65. We examined Mendelian genetic and social modes of transmission of excess longevity (the difference between observed and expected longevity) by varying weighted kinship contributions over different classes of relatives. The genetic component of the variation in excess longevity measured as heritability, h2, was approximately 0.15 (95% confidence interval [CI] 0.12-0.18). Among siblings of probands who reached the 97th percentile of excess longevity (+ 14.8 years, currently age 95 for men and 97 for women), the relative risk of recurrence (lambdas) was 2.30 (95% CI 2.08-2.56). In sibships whose relatives were in the top 15% of the distribution for familial excess longevity, the value of lambdas increased substantially, indicating that considering the longevity of distant relatives may be helpful in the selection of families in which to identify genes influencing aging and longevity.

Measures of familial aggregation as predictors of breast-cancer risk.

BACKGROUND: Several measures of familial disease aggregation have been proposed, but only a few of these are designed to be implemented at the individual level. We evaluate two of them in the context of breast-cancer incidence. METHODS: A population-based cohort consisting of 114 429 women born between 1874 and 1931 and at risk for breast cancer after 1965 was identified by linking the Utah Population Data Base and the Utah Cancer Registry. Two competing methods were used to obtain predictors of familial aggregation of risk: the number of first-degree relatives with breast cancer (NIST) and the familial standardised incidence ratio (FSIR), which weights the disease status of relatives based on their degree of relatedness with the proband. Relative risks were estimated using Mantel-Haenszel. Poisson regression and spline regression methods. The age-dependent hazard function was also estimated. RESULTS: Compared to a baseline category containing 91.5% of the subjects, the 0.7% of subjects identified as high risk using the FSIR criterion had a relative risk of about 2.8, while those identified as high risk using the NIST criterion had a relative risk of 2.0. Moderate-risk subjects had a relative risk of about 1.75 using either criterion. FSIR was a significant predictor of risk even for those with no affected first-degree relatives. No decline in the baseline risk was observed at advanced ages. CONCLUSIONS: FSIR appears to be a better predictor of breast-cancer risk than NIST, particularly for high-risk subjects.

Risk of colon cancer associated with a family history of cancer or colorectal polyps: the diet, activity, and reproduction in colon cancer study.

The Diet, Activity, and Reproduction in Colon Cancer (DARCC) study is a large, multi-center case-control study of colon cancer. We examined family histories of cancer among first-degree relatives obtained by computer-assisted in-person interviews from the DARCC to study the impact of family histories of several cancers and colorectal polyps on colon cancer risk. We examined familial cancer risks both by treating a family history of polyps or cancer as a covariate in a logistic regression model, and by comparing cancer or polyp incidence among relatives of cases to incidence among relatives of controls in a proportional hazards model. There were few differences between the odds ratios (OR) or confidence intervals (CI) generated from logistic regression models and the hazard rate ratios (HRR) generated from the proportional hazards models. Overall, the OR of colon cancer among subjects with a family history of colorectal cancer was 1.77. There were only minor differences in risk by sex, age and subsite. A family history of colorectal polyps also increased risk by about the same amount as a family history of colorectal cancer. The increased risk associated with a family history of polyps did not appear to decrease with age.

Comparison of self-reported and database-linked family history of cancer data in a case-control study.

The authors linked interview data drawn from Utah participants in the Diet, Activity, and Reproduction in Colon Cancer (DARCC) Study (1992-1995) to genealogic and cancer information contained in the Utah Population Database (UPDB). They evaluated the sensitivity of subjects' reports of familial cancers and measured the overall agreement between reported and database records with the kappa (kappa) statistic. They calculated odds ratios from logistic regression to compare the relative risk estimates that would result from use of either data set (or both data sets). Overall, 37.6% (331 of 881) of the Utah DARCC subjects were linked to the UPDB genealogy. High sensitivities were observed for subjects' reports of breast (83%), colorectal (73%), and prostate (70%) cancers, while ovarian (60%) and uterine (30%) cancers were not reported as well. Results for kappa were similar, with values of 0.63 for breast cancer and 0.56 for colorectal cancer. Although the observed kappa s of 0.36 and 0.25 for ovarian and uterine cancers, respectively, exceeded chance expectations, the agreement between subjects' reports and database records was unimpressive. No consistent difference was observed between cases and controls in the accuracy of self-reports. In general, higher sensitivities were observed among younger subjects than older subjects; females reported family histories of cancer only slightly better than males. A college education was not consistently associated with more accurate reporting of family history of cancer. These results indicate that subjects in a case-control study are able to report accurately family histories of several common kinds of cancer and that they can do so without observable recall bias. The accuracy of self-reports may not be adequate for reproductive tract cancers and cancers such as rectal cancer that are frequently confused with cancers of similar organs.

Limits of fetal thyroid risk from radioiodine exposure.

An incident in which a young women became pregnant soon after being treated with 444 MBq 131 I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study (Kerber et al. 1993) indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 of them could be located in the 1980's and were examined with abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 2 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x ray vs. radioiodine).

Microsatellite instability in human colonic cancer is not a useful clinical indicator of familial colorectal cancer.

BACKGROUND & AIMS: Microsatellite instability is a property of most tumors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%-15% of apparently sporadic colorectal cancers, and it has been hypothesized that this instability may indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer. METHODS: Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics. RESULTS: Microsatellite instability was found in 16.5% of tumors. It was predominantly a feature of right-sided tumors (P = 0.003) and was associated with the youngest and oldest ages at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transferase mu 1 null genotype. CONCLUSIONS: Although some very small, and as yet undefined, proportion of colon cancer may be caused by inherited mutations leading to microsatellite instability, tumoral instability by itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.

Impact of family history of colon cancer on development of multiple primaries after diagnosis of colon cancer.

PURPOSE: The purpose of this study was to assess risk of developing multiple primaries after a diagnosis of colon cancer and to determine the impact that having a family history of cancer has on cancer risk. METHODS: Data from the Utah Cancer Registry and the Utah Population Database were used. A cohort of 2,236 first primary colon cancers were observed for the subsequent development of additional primary cancers. RESULTS: We observed a greater than expected incidence of colon, rectal, and pancreatic cancers among the cohort. The standardized incidence ratios were 2.77 (95 percent confidence interval (CI), 2.07-3.70), 2.26 (95 percent CI, 1.34-3.81), and 2.38 (95 percent CI, 1.32-4.30), respectively. Having a family history of colon or rectal cancer did not greatly influence risk of having a multiple primary. However, there was a trend toward increased risk of pancreatic cancer (hazard rate ratios, 1.99; 95 percent CI, 0.67-5.90) and bladder cancer (hazard rate ratios, 2.35; 95 percent CI, 0.77-7.18) among patients with a family history of rectal cancer. We also observed that risk of uterine cancer in the cohort was positively associated with family history of uterine cancer, risk of breast cancer was positively associated with family history of breast cancer, and risk of prostate cancer was positively associated with family history of prostate cancer. CONCLUSIONS: People with colon cancer are at a greater risk of developing colon, rectal, and possibly pancreatic cancer. Although a family history of colon or rectal cancer did not have a large impact on developing other cancers, a family history of other primary cancers did influence risk of other cancers.

The impact of family history of colon cancer on survival after diagnosis with colon cancer.

BACKGROUND: The impact of family history of colon cancer on survival after diagnosis with colon cancer is generally unknown. It is possible that family history is indicative of a genetically inherited form of disease which may alter survival. METHODS: The Utah Population Database was used to evaluate survival after diagnosis with colon cancer among 2236 first primary colon cancer cases. This database includes detailed information about family history and is linked to the Utah Cancer Registry to obtain tumour information. RESULTS: Stage at diagnosis was the primary factor associated with death from all causes and from colon cancer. An older age at diagnosis, being female, and having a tumour in the ascending segment of the colon also were associated with poorer survival, although after adjusting for stage at diagnosis these associations disappeared. Having a family history of colon cancer had little impact on survival patterns although there were suggestions that men who were diagnosed at age < or = 55 were more likely to die from all causes as well as colon cancer if they had a sibling with colon cancer (hazard rate ratio [HRR] 2.50, 95% confidence interval [CI]: 1.03-6.10) relative to men > 55 without a sibling with colon cancer. CONCLUSIONS: From these data it appears that the major factor which increases survival is being diagnosed at an early stage of disease. These data also suggest that younger men who have a sibling with colon cancer may have a different form of colon cancer which increases their risk of dying.

Reproductive factors and colon cancer: the influences of age, tumor site, and family history on risk (Utah, United States).

The Utah (United States) Population Database was used to evaluate the associations between reproductive factors and colon cancer risk and the impact that family history, age at diagnosis, and tumor site have on these associations. From the cohort of (White) women in the database, all first-primary cases of colon cancer (n = 819) and controls who had complete fertility information (n = 3,202) were examined. The majority of tumors (68.6 percent) among women diagnosed at age 64 years or less were in the distal segment of the colon, while among women 65 or older, the majority of tumors (55.7 percent) were proximal. Women diagnosed before age 65 had a lower risk of colon cancer with increasing numbers of liveborn children (odds ratio [OR] = 0.6, 95 percent confidence interval [CI] = 0.3-0.9 for women with five or more children compared with women with one or two children). A long interval between first and second births (first birth-interval) was associated with increased risk of tumors in the distal segment of the colon (OR = 1.4, CI = 1.0-2.0) and among women diagnosed before age 65 (OR = 1.6, CI = 1.0-2.5); a longer, average birth-interval was associated with increased risk of proximal tumors (OR = 1.5, CI = 1.1-2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of family history on ovarian cancer risk. The Utah Population Database.

OBJECTIVE: To estimate the relative risks and population attributable risks of ovarian cancer associated with family histories of cancer at several sites. METHODS: A matched case-control analytic study (662 cases, 2647 controls), employing the Utah Population Database, a genealogy of approximately 1 million individuals linked to cancer incidence data from the Utah Cancer Registry. Family history was assessed using kinship order and a kinship-weighted familial standardized incidence ratio statistic. RESULTS: Family histories of ovarian, uterine, breast, and pancreatic cancer were significantly associated with increased risk of ovarian cancer. The relative risk of ovarian cancer was 4.31 (95% confidence interval [CI], 2.35 to 7.90) for women with a first-degree relative with ovarian cancer, 2.12 (95% CI, 1.19 to 3.78) for women with an affected second-degree relative, and 1.48 (95% CI, 0.98 to 2.24) for women with an affected third-degree relative. The odds ratio (OR) was 2.06 (95% CI, 1.44 to 2.93) for those with the highest familial standardized incidence ratio. No age differences were observed between cases with and without a family history of ovarian cancer. There was substantial heterogeneity of family history effects by cell type. Increased parity was not protective among women with a strong family history of cancer at the sites studied (OR, 1.11; 95% CI, 0.38 to 3.26), although it was protective among women without a family history of these cancers (OR, 0.29; 95% CI, 0.11 to 0.62). CONCLUSIONS: The risk of ovarian cancer was substantially increased among women with family histories of ovarian, uterine, pancreatic, and, to a lesser degree, breast cancer. Among women with family histories of any of these cancers, the risk of ovarian cancer is not diminished by high parity.

Response rates among control subjects in case-control studies.

Response rates are an important component of epidemiologic research. The purposes of this study are (a) to evaluate how response rates are defined and calculated for control subjects in epidemiologic case-control studies, and (b) to explore factors that may impact response in epidemiologic studies. Our results show that the method of control subject selection has an impact on study response. Gender of respondent does not appear to impact response rates. However, response rates are generally worse for individuals less than 45 years old. Methods used to calculate response have a great impact on "response rate"; therefore, it is important for researchers to define exactly what the reported response rates represent and how they are derived so that data can be interpreted appropriately.

Method for calculating risk associated with family history of a disease.

A method is described for estimating excess relative risks of a disease from familial factors. Beginning with population-based series of cases and controls, a cohort of each subject's relatives is formed and checked for disease against a population based registry. The disease experience of the cohort formed from each subject's relatives is summarized as a kinship-weighted familial standardized incidence ratio (FSIR). The FSIR's are used as exposure estimates in conditional linear excess relative risk models, which may be used not only to screen for significant familial disease aggregations, but also to estimate relative risks, population attributable risks, and gene-environment interactions. The method is demonstrated on 4083 breast cancer cases from Utah and a set of matched controls.

Family history of cancer and colon cancer risk: the Utah Population Database.

BACKGROUND: Family history of colon cancer has been shown to be related to the risk of developing colon cancer. The impact that a comprehensive family history of colon or other cancers has on the risk of colon cancer has not been thoroughly studied. PURPOSE: The purpose of this study was to assess the risk of developing colon cancer associated with having a family history of colon, rectal, breast, ovarian, endometrial, or prostate cancer. METHODS: A case-control study was conducted using data from the Utah Population Database. Case patients had first primary colon cancers (n = 2543). Three control subjects per case were individually matched to case patients on year of birth, place of birth, marital status, and sex. RESULTS: Those case patients with the highest familial standardized incidence ratio were at an increased risk of developing colon cancer (for men, odds ratio [OR] = 2.51 and 95% confidence interval [CI] = 1.88-3.29; for women, OR = 2.90 and 95% CI = 2.17-3.82). A second- or third-degree relative with colon cancer increased risk from 25% to 52%. Risk associated with family history was greater in those patients diagnosed before age 50 (for men, OR = 3.61 and for women, OR = 7.18) than in those diagnosed at 50 or more years of age (for men, OR = 2.44 and for women, OR = 2.73). The risk associated with a family history of colon cancer was greatest for the distal segment of the colon. Women were at an increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.59; 95% CI = 1.25-2.03), uterine (OR = 1.50; 95% CI = 0.99-2.26), ovarian (OR = 1.63; 95% CI = 1.41-1.89), or prostate (OR = 1.49; 95% CI = 1.21-1.82) cancer; men were at increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.30; 95% CI = 1.02-1.66), uterine (OR = 1.96; 95% CI = 1.34-2.87), or ovarian (OR = 1.59; 95% CI = 0.90-2.81) cancer. CONCLUSIONS: These findings support previous observations that people with a family history of colon cancer are at increased risk of colon cancer. Those with a second- or third-degree relative with colon cancer or a first-degree relative with breast, ovarian, uterine, or prostate cancer also have an increased risk of developing colon cancer. IMPLICATIONS: These data support the recommendations that individuals who have a first-degree, and possibly a second- or third-degree, relative with colon cancer should have regular screening for colon cancer.

Founder effect: assessment of variation in genetic contributions among founders.

We present a Monte Carlo method for determining the distribution of founders' genetic contributions to descendant cohorts. The simulation of genes through known pedigrees generates the probability distributions of contributed genes in recent cohorts of descendants, their means, and their variances. Genealogical data from three populations are analyzed: the Hutterite population of North America, the island population of Sottunga from the Aland archipelago, and the large Utah Mormon population. Two applications of the Monte Carlo method are presented. First we investigate the relative opportunity for founder effect in the three populations, which have dissimilar pedigree structures and dissimilar disease gene frequencies. Second, we measure the reproductive success of population founders in terms of the number of genes they contribute to a cohort some number of generations descendant and compare the effects of polygyny versus monogamy on reproductive success. The distribution of Hutterite founder contributions describes the context for a classic founder effect. Hutterite founders have a higher probability of leaving no genes in the population (72%) than Sottunga (48%) and Mormon (48%) founders. However, founder genes that survive among Hutterite descendants do so in larger numbers on average than founder genes in the other two populations. Greater variation among monogamous Hutterite founders compared with Mormon polygynous founders demonstrates that polygyny alone does not maximize the variance in reproductive success; other population characteristics are at least as important for determining variability among individuals in their genetic contributions to a gene pool. Our findings make it difficult to appreciate the reproductive advantage of polygyny in the Mormon population. Although the expected gene contributions and their variances were larger for polygynous founders compared with other Mormons, the main effect of polygyny was to increase the probability that any polygynist left a few genes among descendants. Furthermore, only 12% of the variation in the genetic contributions of Mormon founders is explained by their number of offspring. We conclude that shallow genealogical data (from one or a few generations) provide a poor measure of long-term reproductive success.

Gender of the first offspring, age at diagnosis, and survival with breast cancer (Utah, United States).

We examined the relationship between the survival of women with breast cancer and the gender of their first children using a genealogy-based survival analysis. The study group consisted of 2,155 parous women diagnosed in Utah (United States) with first primary breast cancers (excluding in situ tumors). We calculated hazard rate ratios (HRR) which were adjusted for stage, median survival times, and proportions surviving for three-, five-, and 10-year intervals stratified by age at diagnosis. Median survival among women diagnosed under the age of 45 was 171 months if the first child was female, but only 66 months if the first child was male (HRR = 1.66, 95 percent confidence interval = 1.07-2.57, for male children). For women diagnosed at age 45 or older, all survival times were similar, although women whose first child was male had slightly longer median survival time. These findings suggest that the gender of the first child has a strong influence on survival among women diagnosed under 45 years of age, but not among those diagnosed later in life. Gender of the first offspring may be a useful clinical indicator of prognosis and survival and may provide insights into etiologic and promotional factors for breast cancer.

Is survival among women diagnosed with breast cancer influenced by family history of breast cancer?

In this study, we examine the association between having a family history of breast cancer and survival after diagnosis with breast cancer. Data for this study were from the Utah Population Database, a linked database consisting of genealogy data of Mormon pioneer families, Utah Cancer Registry data, and Vital Statistics data. We observed that women who had a mother with breast cancer were more likely to die of any cause than women without a mother with breast cancer [hazard rate ratio (HRR) = 1.36, 95% confidence limits (CL) = 1.04, 1.79], as were women with over 30 female relatives with breast cancer (HRR = 1.69, 95% CL = 1.16, 2.45). Similar findings were observed for women dying of breast cancer. Other indicators of family history were not associated with survival except within specific age groups. Women diagnosed with breast cancer at age 50 or before had poorer survival if they had a family history of breast cancer. Relative risk estimates were 1.54 (95% CL = 0.98, 2.41) for first degree relative, 1.55 (95% CL = 0.87, 2.78) for mother, and 2.65 (95% CL = 1.23, 5.74) for more than 30 female relatives with breast cancer.

A cohort study of thyroid disease in relation to fallout from nuclear weapons testing.

OBJECTIVE: To estimate individual radiation doses and current thyroid disease status for a previously identified cohort of 4818 schoolchildren potentially exposed to fallout from detonations of nuclear devices at the Nevada Test Site between 1951 and 1958. DESIGN: Cohort analytic study. SETTING: Communities in southwestern Utah, southeastern Nevada, and southeastern Arizona. PARTICIPANTS: Individuals who were still residing in the three-state area (n = 3122) were reexamined in 1985 and 1986, and information on the subjects' and their mothers' milk and vegetable consumption during the fallout period was obtained by telephone interview (n = 3545). After exclusions to eliminate missing data and confounding factors, 2473 subjects were available for analysis. MAIN OUTCOME MEASURES: Individual radiation doses to the thyroid were estimated by combining consumption data with radionuclide deposition rates provided by the US Department of Energy and a survey of milk producers. Relative risk models adjusted for age, sex, and state were fitted using maximum likelihood to period prevalence data for thyroid carcinomas, neoplasms, and nodules. RESULTS: Doses ranged from 0 mGy to 4600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19), with an increase in excess relative risk of 0.7% per milligray. A relative risk for thyroid neoplasms of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for carcinomas and nodules. CONCLUSIONS: Exposure to Nevada Test Site-generated radioiodines was associated with an excess of thyroid neoplasms. The conclusions are limited by the small number of exposed individuals and the low incidence of thyroid neoplasms.

A comprehensive evaluation of family history and breast cancer risk. The Utah Population Database.

OBJECTIVE: The purpose of this study is to assess the impact of family history on the risk of developing breast cancer. DESIGN: A case-control study design was used. SETTING: To provide a comprehensive assessment of family history risk, we used the Utah Population Database, a linked database compiled of genealogy data of the descendants of Mormon pioneer families, cancer data from the Utah Cancer Registry, and mortality data from the Utah Department of Vital Statistics. PATIENTS: All women diagnosed with breast cancer who were in the genealogy database and the Utah Cancer Registry were included. Controls were women selected from the genealogy, who like cases had no record of previous cancer. They were matched to the cases by age and place of birth. OUTCOME: Several definitions of family history were used. The total familial risk variable, developed to work effectively in the Utah Genealogy Database, accounts for all family members, their degree of relatedness to the case, and the amount of time they were observed for possible cancer diagnosis. RESULTS: A threefold increase in risk, estimated by the odds ratio (OR), of breast cancer among those with the highest family history score (6% of cases) was observed when compared with those with the lowest family history score. The OR for women with a first-degree relative with breast cancer was 2.45 (95% confidence interval [CI], 1.84 to 3.06). If the nearest relative was a second-degree relative, the OR was 1.82 (95% CI, 1.39 to 2.24); if the nearest relative was a third-degree relative, the OR was 1.35 (95% CI, 1.07 to 1.64). A slightly greater risk was observed if the first-degree relative was a woman's mother (OR, 2.44; 95% CI, 1.77 to 3.42) rather than a sister (OR, 2.01; 95% CI, 1.66 to 2.43). Among subjects diagnosed before the age of 50 years, the disease experience of relatives prior to age 50 was most important, while for older subjects the experience of relatives of all ages was of roughly equal importance. Women who developed contralateral breast cancer within 3 years of initial diagnosis were nearly 10 times as likely as women without breast cancer to have a first-degree relative with breast cancer. Based on the risk estimates in this study, we have estimated that approximately 17% to 19% of breast cancer in the population could be attributed to family history. Women who had a first-degree relative with colon cancer had a 30% increased risk of breast cancer. CONCLUSIONS: In this study population, women with a family history of breast cancer, even if the nearest relative with breast cancer is a third-degree relative, are at increased risk of the disease.

Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study.

Previous studies reported an association between leukemia rates and amounts of fallout in southwestern Utah from nuclear tests (1952 to 1958), but individual radiation exposures were unavailable. Therefore, a case-control study with 1177 individuals who died of leukemia and 5330 other deaths (controls) was conducted using estimates of dose to bone marrow computed from fallout deposition rates and subjects' residence locations. A weak association between bone marrow dose and all types of leukemia, all ages, and all time periods after exposure was found. This overall trend was not statistically significant, but significant trends in excess risk were found in subgroups defined by cell type, age, and time after exposure. The greatest excess risk was found in those individuals in the high-dose group with acute leukemia who were younger than 20 years at exposure and who died before 1964. These results are consistent with previous studies and with risk estimates for other populations exposed to radiation.