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Biomedical subjects

P Lichtenstein

Publications and source records attributed to P Lichtenstein.

At least 55 records · Page 3Linked to original sources

Cancer in twins: genetic and nongenetic familial risk factors.

BACKGROUND: Familial clustering has been observed for cancers that occur at specific sites. Most findings, which leave little doubt about the involvement of a heritable (i.e., genetic) component in the development of some cancers, are based on data from "cancer-prone" families or interviews with subjects who have cancer. The study of twins should be of value in cancer epidemiology because twins either are genetically identical or share half of their segregating genes. PURPOSE: We linked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk. METHODS: Same-sex twin pairs with both individuals alive and living in Sweden in 1959-1961 or 1970-1972 were identified in the old cohort (born from 1886 through 1925) or the young cohort (born from 1926 through 1958), respectively, of the Swedish Twin Registry; pairs for whom zygosity (i.e., the number of eggs that gave rise to the twins) could be determined were considered further. The association of cancer with combined genetic and nongenetic familial factors was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer at one of several specific sites with pairs in which neither twin had that cancer. Heritable effects alone were tested by comparing monozygotic (one egg) and dizygotic (two eggs) twin pairs. Statistical methods used in quantitative genetics and standard methods for epidemiologic research were used in parallel to analyze the data. RESULTS AND CONCLUSIONS: In the 10503 twin pairs from the old cohort, 361.7 cases of malignant cancer were identified; 918 malignant cancers were identified in the 12883 twin pairs from the young cohort. When cancer sites with a total number of at least 200 cases and at least one twin pair concordant (i.e., both twins affected) for the site were evaluated, namely, cancers of the stomach, colon and rectum, lung, female breast, and prostate, as well as total cancer, profound genetic and/or nongenetic familial effects were identified in twins from the old cohort. Similar findings were obtained for twins in the young cohort for cancers of the prostate and female breast, as well as for total cancer. Genetic and nongenetic familial effects were also identified in twins from both cohorts for in situ cancer of the cervix. The increase in risk of colon and rectum, breast, cervical, and especially prostate cancer, but not stomach or lung cancer, tended to be greater if a monozygotic rather than a dizygotic twin were affected. IMPLICATIONS: The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general.

Adult↗

Can personality explain genetic influences on life events?

Previous research in the Swedish Adoption/Twin Study of Aging (SATSA) has found genetic influences on life events (R. Plomin, P. Lichtenstein, N.L. Pedersen, G.E. McClearn, & J.R. Nesselroade, 1990). The present study extends this finding by examining sex differences in genetic and environmental contributions to life events and by examining personality as a mediator of genetic influences on life events in SATSA. Analyses were based on 320 twin pairs, including identical and fraternal twins reared together and apart (mean age = 58.6 years). Controllable, desirable, and undesirable life events were revealed significant genetic variance for women. There was no significant genetic variance for either sex for uncontrollable events. Multivariate analyses of personality (as indexed by Neuroticism, Extraversion, and Openness to Experience) and life events suggest that all of the genetic variance on controllable, desirable, and undesirable life events for women is common to personality. Thus, in this sample of older adult women, genetic influences on life events appear to be entirely mediated by personality.

Adult↗

Genes, environments, and sex: factors of importance in atopic diseases in 7-9-year-old Swedish twins.

Various atopic manifestations among adults have been shown to be influenced mainly by genetic factors. With the increase in prevalence of atopic diseases in recent years, especially among children, a great deal of attention has been given to environmental causes. In a study of 1480 Swedish twin pairs, 7-9 years old, we examined the importance of genetic and environmental factors in asthma, hay fever, eczema, and urticaria. Structural equation model fitting showed 33-76% of the variation in liability to the diseases to be due to genetic effects. Shared environmental effects were also important for hay fever and urticaria in both sexes and for eczema among girls. The clustering of atopic disease in families was almost entirely due to a common set of genes, but each disease manifestation also seemed to have specific genes of importance. Investigation of unlike-sex twins showed that boys had a higher cumulative incidence of asthma and hay fever than girls, whereas girls had a higher incidence of eczema. Thus, it may be concluded that although genetic factors are of major importance in atopic manifestation in children, both environmental and sex-related factors play a role.

Asthma↗

Twin births to mothers who are twins: a registry based study.

OBJECTIVES: To estimate the risk of having twin infants for mothers who are twins; to investigate the genetic influence on twinning. DESIGN: Retrospective study of multiple births in two nationwide registries. SETTING: Sweden. SUBJECTS: Multiple births among 31,586 deliveries between 1973 and 1991 to women who were twins. MAIN OUTCOME MEASURES: Numbers of monozygotic and dizygotic twin births expected and estimated. RESULTS: Women who are dizygotic twins have a moderately increased risk of having twins (relative risk 1.30, 95% confidence interval 1.14 to 1.49) which seems to be completely the result of dizygotic twinning. When a mother is a monozygotic twin, her risk of having twins of the same sex is significantly increased (1.47; 1.10 to 1.97). This is the result of an excess of monozygotic twins (39 pairs estimated, 18 expected). CONCLUSIONS: Women who are twins have an increased risk of giving birth to twins. Genetic components of monozygotic and dizygotic twinning seem to be independent.

Female↗

A co-twin--control study of response to widowhood.

The effects of long-term and recent conjugal bereavement were investigated in a sample of 2,104 Swedish twins followed between 1984 and 1993. In co-twin-control analyses, the bereaved twin experienced significantly more depressive symptoms, more loneliness, and less life satisfaction than the married co-twin. This association existed for recently widowed (< 3 years) of both sexes. Long-term widowed (> 5 years) reported more loneliness than married individuals, and for women there was also a difference in life satisfaction. There were no effects of bereavement on perceived physical health. Individual analyses, which included all respondents regardless of the co-twin's bereavement status, showed the same pattern of results. There was also evidence for an anticipation effect of widowhood indicated by elevated depressive symptoms prior to the spouse's death. Finally, longitudinal analyses showed that it is more stressful to be bereaved when young-old than old-old, but revealed no age differences in adaptation.

Age Factors↗

Physical and mental health related to dental amalgam fillings in Swedish twins.

In the past years increasing attention has been paid to possible adverse health effects of mercury exposure from dental amalgam fillings. To evaluate possible health effects from amalgam fillings, dental status registered by specially trained nurses was obtained from 587 subjects included in the ongoing Swedish Adoption/Twin Study of Aging (SATSA). Data on physical and mental health were collected and memory function tested. Mean age was 66 years (SD 9, range 46-89). In the entire material, 25% of the individuals had no own teeth and in the group with own teeth the median number of teeth surfaces filled with dental amalgam was 15 (range 0-65). Analyses of associations between number of surfaces filled with dental amalgam and a number of scales estimating somatic and mental health and memory functions were performed both for the entire group and for individuals having at least 12 teeth. Regardless of the sample, no negative effects on physical or mental health were found from amount of dental amalgam, even after controlling for age, gender, education and number of remaining teeth. When using a co-twin control design with twin pairs discordant for amalgam exposure, no negative health effects associated with dental amalgam were detected. This study does not indicate any negative effects from dental amalgam on physical or mental health or memory functions in the general population over 50 years of age.

Age Factors↗

Dimensions of occupations: genetic and environmental influences.

This study investigates the dimensions of occupation, and distances between occupational categories, by using intra-pair differences in adult occupational position for identical twins reared apart. Status and farm dimensions of occupation were identified. The results validate the use of occupational status as a dimension of occupational position. The causes of individual differences for the derived status dimension were also evaluated, based on groups of identical and fraternal twins reared apart or together. Genetic effects accounted for a substantial amount of the variance in occupational status for men, while shared and non-shared environmental effects were of about equal importance. For women, genetic effects were less important, and shared and non-shared environmental effects accounted for more of the variation. The results confirm that genetic effects are important sources of the familial resemblance often found for occupational status for men.

Adoption↗

Variability and stability in cognitive abilities are largely genetic later in life.

The powerful quantitative genetic design of identical and fraternal twins reared apart (112 pairs) and matched twins reared together (111 pairs) was employed to assess the extent of genetic influence on individual differences in cognitive abilities during the last half of the life span. General cognitive ability yielded a heritability estimate of about .80 in two assessments 3 years apart as part of the Swedish Adoption/Twin Study of Aging. This is one of the highest heritabilities reported for a behavioral trait. Across the two ages, average heritabilities are about .60 for verbal tests, .50 for spatial and speed-of-processing tests, and .40 for memory tests. For general cognitive ability, the phenotypic stability across the 3 years is .92 and stable genetic factors account for nearly 90% this stability. These findings suggest that general cognitive ability is a reasonable target for research that aims to identify specific genes for complex traits.

Aging↗

Genetic and environmental influences on perceptions of organizational climate.

Genetic and environmental influences on perceptions of organizational climate were assessed by using a 4-group twin design. Data were obtained as part of the Swedish Adoption/Twin Study of Aging. The Work Environment Scale (WES) was used to evaluate perceptions of organizational climate. A measure of job satisfaction was also used to evaluate the effects of genes and environments on job attitudes. Maximum likelihood estimates of genetic and environmental influence suggested significant genetic effects for Supportive Climate--1 factor resulting from a factor analysis of the WES--but not for a second factor, Time Pressure. Significant environmental effects were found for both Supportive Climate and Time Pressure. Genetic effects were not significant for job satisfaction. The relevance of findings to organizational climate research and personnel selection are discussed.

Adult↗

Socioeconomic status and physical health, how are they related? An empirical study based on twins reared apart and twins reared together.

This investigation used the powerful combined twin and adoption design to assess the validity of three different hypotheses--social causation, childhood experiences, and health selection--on the origin of the association between socioeconomic status (SES) and health. The sample contains 99 pairs of monozygotic twins reared apart, 166 pairs of monozygotic twins reared together, 238 pairs of dizygotic twins reared apart, and 221 pairs of dizygotic twins reared together, who completed questionnaire items concerning their SES and health status. Genetic effects, environmental effects unique to the individual, as well as environmental effects shared by twins were involved in mediating the associations between SES and health. However, the relative importance of these effects varied for the different associations depending on the measures of health and SES respectively. The results indicate that social causation, childhood experiences, and health selection may all be important for the association between SES and health. It is argued that these hypotheses are not contradictory, rather the relationship between the complex dimensions SES and health may be explained by several different causes.

Adult↗

Safety and efficacy of treatment of pediatric cholesteryl ester storage disease with lovastatin.

The aim of this study was to prospectively assess the safety and efficacy of lovastatin in the treatment of cholesteryl ester storage disease in siblings who were ages 11.6 and 5 y at the beginning of treatment. Mean total and LDL cholesterol in the male proband, 7.40 and 5.68 mmol/L, respectively, on diet alone, fell 30% to 5.2 (p < or = 0.001) and 31% to 3.9 mmol/L (p < or = 0.001) on lovastatin 40 mg/d over 3.3 y, with simultaneous resolution of hepatosplenomegaly. In his sister, on lovastatin 20 mg/d for 1.5 y, total and LDL cholesterol fell, but not significantly; her hepatosplenomegaly was also reduced on treatment. Lovastatin was well tolerated without overt side effects or complications and without adverse changes in liver function tests or creatine phosphokinase. Normal and expected accretion of height and weight occurred during the treatment period for both children. Lovastatin appears to be a safe and effective treatment for pediatric cholesteryl ester storage disease.

Child↗

Genetic influence on life events during the last half of the life span.

Genetic influence on perceptions of major events later in life was assessed with a combination of twin and adoption designs as part of the Swedish Adoption/Twin Study of Aging (SATSA). The SATSA design includes 4 groups totaling 399 pairs of same-sex twins: identical and fraternal twins reared apart and matched twins reared together. The average age of the twins was 59 years. The results demonstrate significant genetic influence on reports of the occurrence of life events, especially for controllable events in which the individual can play an active role. Maximum likelihood model-fitting estimates of genetic influence indicate that 40% of the variance of the total life events score is due to genetic differences among individuals. How genetic factors can affect life experiences and directions for future research are discussed.

Humans↗

Calcium-regulating hormones and minerals from birth to 18 months of age: a cross-sectional study. I. Effects of sex, race, age, season, and diet on vitamin D status.

The influence of sex, race, age, season, and diet (cow's milk formula v human milk) on the vitamin D and vitamin D-binding protein status in infants less than 18 months of age was investigated in this cross-sectional, prospective study of 198 infants. No differences by sex were observed in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein concentrations. By race, black infants had significantly elevated serum 1,25-dihydroxyvitamin D levels relative to white infants. By age, vitamin D-binding protein concentrations increased with increasing age. By season, serum 25-hydroxyvitamin D concentrations were low in winter, whereas 1,25-dihydroxyvitamin D and vitamin D-binding protein were high in winter compared with summer. By diet, formula-fed infants had higher serum concentrations of all measured vitamin D metabolites and vitamin D-binding protein than human milk-fed infants. Thus, race, age, season, and diet exert, individually or in combination, different and significant effects on vitamin D metabolites; these should be considered in assessing infant vitamin D status.

24,25-Dihydroxyvitamin D 3↗