Familial Aggregation Of Cancer Research Articles

Coefficients of relationship by isonymy among registrations for five common cancers in Scottish males.

The aim was to assess the relative importance of genetic factors in carcinoma of the stomach, colon, rectum, prostate, and bladder in Scottish males. Cancer cases and controls were compared in terms of the coefficient of relationship by isonymy (Ri). Surname distributions for cancer cases were derived from the Scottish Cancer Register for the years 1959-85. Control distributions were derived from all births, marriages and deaths in Scotland for 1976. Analysis was carried out on a total of 60,933 cancer registrations and 101,836 births, marriages, and deaths over the 12 local government regions of Scotland. Comparisons of Ri within and between regions indicated that inherited susceptibility was of greatest importance in carcinoma of the prostate and colon, of intermediate importance in carcinoma of the rectum and stomach, and of minimal importance in carcinoma of the bladder. Familial aggregation of cancers was most pronounced in Highland, Tayside, and Borders Regions. For Highland, this appeared to be the result of region-specific familial influences, while Tayside and the Borders shared genetic factors contributing to cancer aetiology with neighbouring regions in south east Scotland. Surname analysis is a simple but useful tool for studying population genetic structure and its relationship to disease incidence.

Familial Aggregation of Cancer from Proband Cases with Childhood Adrenal Cortical Carcinoma1

Family pedigree of Li‐Fraumeni syndrome was investigated from probands with childhood adrenocortical carcinoma in Japan. From 47 probands, 7 families had 3 or more cancer cases at ages less than 45 years within the first generation; one satisfied Li's original criteria, two were acceptable because of multiple primary cancer in the probands, and others showed an aggregation of cancers with onsets at early ages, though no sarcoma of mesenchymal origin was found. A significantly higher occurrence of cancer in the mothers of the probands, especially of the breast, was consistent with reports from the USA, and liver cancer, osteosarcoma and lung cancer among family members under the age of 45 also showed a higher frequency than in the general population. Similarities and differences between Japanese and Caucasian cases are discussed.

Survival models for familial aggregation of cancer.

It has recently been shown that the relative risks of the order of 2 to 4 that are frequently found for cancer among relatives of affected cases are unlikely to be explainable by shared environmental risk factors. Classical methods of epidemiological analysis are not well suited to such analysis because they assume that the outcomes of each individual are independent. Classical methods of genetic analysis, on the other hand, are limited in their handling of environmental factors and variable ages of onset. The recent development of random effects models for survival analysis, however, appears to bridge this gap. Specifically, a proportional hazards model is postulated for the effects of measured covariates and of one or more components of frailty that are unmeasured but assumed to have some common distribution and known covariance structure within each family. From these assumptions, the posterior expectation of the hazard for each individual can be derived, given the covariate value and the observed and expected disease history of the family. These are then treated as known in a standard partial likelihood analysis; this is essentially a form of expectation-maximization algorithm. However, this does not provide a valid estimate of the covariance matrix because it fails to take account of the variability in the estimates of the frailties; an alternative approach using the imputation-posterior algorithm is suggested. This paper describes extensions of this approach to multivariate frailty distributions, modifications for application to pedigree and case-control studies, some simulation results, and applications to studies of breast cancer in twins and of lung cancer in relation to family smoking habits.

Correspondence in cancer history between husbands and wives.

To study the effect of the environments shared by spouses on the development of cancer and some chronic diseases, we analyzed the correspondence of disease history in 21,592 fathers and mothers using the baseline data of a population-based cohort study. The observed number of cases (O) whose parents had the same disease history was statistically significantly greater than the expected (E); the O/E ratio was 1.53 (95% confidence interval (CI): 1.43-1.63) for all malignant neoplasms, 5.22 (95% CI: 2.81-9.70) for esophageal cancer, 1.63 (95% CI: 1.37-1.93) for stomach cancer, 3.01 (95% CI: 1.89-4.79) for colorectal cancer, 3.90 (95% CI: 2.75-5.53) for liver cancer, 3.14 (95% CI: 1.95-5.08) for lung cancer, 6.73 (95% CI: 2.53-17.87) for bladder cancer, 1.66 (95% CI: 1.54-1.78) for apoplexy and 1.67 (95% CI: 1.51-1.86) for heart disease. The results of the present study suggest that the environmental factors shared by family members for a long time may contribute to familial aggregation of cancer and some chronic diseases.

Familial aggregation of cancer in Laredo, Texas: a generally low-risk Mexican-American population.

Genealogies for the Mexican-American city of Laredo, Texas, have been assembled by computer from individual civil and church records of birth, marriage, and death. Documentation is available on vital events in the lives of over 300,000 individuals, about 80% of the city population from 1870-1981. These data were collected to determine the degree to which death from cancer is more clustered in families than would be expected by chance alone; methods specific to this data base have been developed to accomplish this task. A statistically significant excess of familial cancer was observed overall when all cancer sites were pooled, but no evidence was observed for excess familial risk at single sites except for breast cancer and perhaps for ovarian cancer. The excess of breast cancer risk is comparable to that observed in other populations. A few site-combinations manifest excess familial risk, most notably those involving and dominated by breast cancer and certain digestive system sites. We do not confirm the degree of familiarity observed elsewhere for cancers of the lung, colorectum, stomach, or other sites in this generally low-risk population. Even where we find evidence of excess risk, the degree of excess is small and the number of multiply affected families too small to test etiologic models by segregation analysis. The absence of excess familial risk does not appear to be due to inadequate numbers of cases, since breast cancer is familial with no more occurrences in Laredo than other sites. These results differ to some extent from those found in a similar study of Utah Mormons, but it is unclear whether this is because of differences in risk patterns or statistical properties of the analytic methods used in the two studies.

Site Distribution of Cancer Deaths in Husband-Wife and Sibling Pairs

The problems of determining the importance of environmental and genetic factors contributing to observed familial aggregations of cancer are discussed. The distributions of 29 site classifications in 51 husband-wife pairs, 60 brother-sister pairs, 76 sister-sister pairs, and 44 brother-brother pairs dying of cancer are presented. The total number of pairs matched for detailed site on the death certificate for each type of pairing is compared to an expected number computed from the data in this study. Only the brother-sister pairing failed to show a significant excess of matched pairs. The fact that husband-wife pairings showed an excess suggests that common environment and common heredity should be considered in the explanation of observed familial aggregation of cancer. The Appendix indicates the derivation of the expectations of the sums of matched pairs and their variances for the case of the symmetrical and asymmetrical contingency table. Appropriate chi-square formulas are given for testing the deviations of the observed number of matched pairs from their expectations.