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J Chang-Claude

Publications and source records attributed to J Chang-Claude.

At least 73 records · Page 4Linked to original sources

Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers.

Female carriers of mutations in the BRCA1 gene on chromosome 17q have a very high risk of developing breast and/or ovarian cancer during their lifetime. There is, however, little knowledge of to what extent non-genetic risk factors, such as age at menarche, age at first birth, and body mass index, alter the age at onset of disease. We identified individuals showing a high probability of linkage to BRCA1 and examined the effect of other known risk factors on disease risk. A total of 43 families with at least three breast or ovarian cancer cases, including two affected before 60 years of age, were studied for linkage to the susceptibility locus BRCA1. Blood samples from relevant family members were used to genotype for at least three chromosome 17q polymorphic markers. Information on reproductive history, hormone use and lifestyle factors was collected from female members using a self-administered questionnaire. Diagnoses of breast and ovarian cancer were verified through pathology reports and paraffin blocks were obtained when available. Multipoint LOD (logarithm of the odds) scores were calculated and individuals from 10 families with a posteriori probability for linkage greater than 0.90 were used for further analysis. Forty-six BRCA1 carriers were identified by the disease haplotype; 30 were affected with breast cancer and 5 with ovarian cancer. Proportional- hazards analysis of age at onset of breast cancer yielded increased relative risks of 1.74 for early age at menarche (< 14 years), 1.58 for late age at first birth (> or = 25 years) or nulliparity, and 2.78 for recent year of birth (> or = 1940); however, none of the risk estimates was statistically significant. When both breast and ovarian cancer were considered as disease endpoints, the birth cohort effect was stronger and age at first birth showed no effect. Our data provide some evidence that reproductive risk factors for breast cancer have an effect on age at onset for BRCA1 carriers. However, considering that our analyses were based on limited numbers, these results warrant further clarification.

Adult↗

Comparison of information on occupation and lifestyle habits obtained from European man-made vitreous fibre production workers and their relatives.

BACKGROUND: Studies of the aetiology of fatal diseases often rely on data obtained from relatives, which can cause loss of precision and introduce bias. We assessed the quality of such information on demographics, occupation, smoking and alcohol habits. METHODS: We compared contemporary interviews, based on a structured questionnaire, with male workers from the man-made vitreous fibre production industry in four European countries and their relatives. The participation rate was 63% (74 pairs of workers and relatives). RESULTS: Only minor differences in the ability to answer the questions appeared among workers and relatives, except for specific occupational questions. There was moderate to excellent agreement for demographics, residential and work history (kappa or intraclass correlation range: 0.44-0.98). For smoking habits, beer and wine consumption the agreement was good to excellent (range: 0.59-0.99). In particular, number of different residential areas, jobs, industries, and duration of wine drinking were significantly underreported by the relatives. No general determinant for reduced agreement appeared. CONCLUSIONS: In general, the quality of information obtained from relatives appeared good. However, information on specific occupational exposures may be improved by supplementing the information from relatives with details obtained from colleagues, occupational hygiene experts or occupation-exposure matrices.

Adolescent↗

Familial aggregation of oesophageal cancer in a high incidence area in China.

BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.

Aged↗

Cancer mortality among man-made vitreous fiber production workers.

We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.

Aged↗

[Molecular genetics of hereditary breast carcinoma].

Breast cancer is the most common malignancy among women. Genetic predisposition is considered to account for 5-10% of all cases while the majority of these cancers are sporadic and caused by complex interactions of exogenous and endogenous factors. The inherited predisposition can be due to germline mutations in one of several cancer susceptibility genes. For high risk families the two most important genes are BRCA1 on chromosome 17q, which confers a high risk of both, breast and ovarian cancer and BRCA2 on chromosome 13 associated with high penetrance of breast cancer but lower risk of ovarian cancer. A high risk of breast cancer is conferred by mutations in the p53 tumor suppressor gene as part of the rare Li-Fraumeni-syndrome, and possibly also by the estrogen receptor gene. Other cancer genes associated with a less increased risk of breast cancer are the autosomal recessive ataxia telangiectasia (AT) gene and the HRAS1 gene. Germline mutations in BRCA1 and BRCA2 account for the majority of families with multiple cases of breast and/or ovarian cancer and also at least 10% of cases below the age of 40 years. Genetic testing for BRCA1 mutations is not generally recommended except for women with a strong family history. The aim for the management of familial breast cancer should be the establishment of interdisciplinary teams to cover genetic counseling, molecular analysis, onco-surgical therapy, psychosocial support and clinical follow-up.

BRCA1 Protein↗

Estimating disease risks for individuals with a given family history in different populations with an application to breast cancer.

For many chronic diseases, including most of the common cancers, a family history is known to be a strong independent risk factor. For breast cancer, estimation of risk as a function of family history is considered to provide useful risk assessment for women with a family history of breast cancer. Detailed tables that predict the cumulative risk of breast cancer at specific ages based on various combinations of family history have been constructed for the American white population. Most chronic diseases, however, have a multiple etiology, with multiple genetic and environmental factors. Family history can thus be a result of different susceptibility loci and the aggregation of sporadic cases by chance. Since the relative contribution of the genetic factor may differ in different populations, these tables may not be directly applicable to other populations. We present a method to decompose available estimates of risk based on family history for an arbitrary disease into probabilities for genotype frequency given a particular family history and for disease probabilities by genotype carrier status. These can be reconstructed to obtain risk estimates for different populations. Implicit assumptions are made in the estimation process. These are based on the current state of knowledge and can be updated as further knowledge accumulates.

Adult↗

Longitudinal study of the effects of pregnancy and other factors on detection of HPV.

OBJECTIVE: An epidemiologic study of 108 pregnant and 192 non-pregnant women was carried out to determine the effects of pregnancy and other factors on the detection of HPV infection, since both or larger numbers of pregnancies and HPV infection are known to be risk factors for cervical cancer. PATIENTS AND METHODS: Study participants were followed up at 3-months intervals for a period of 15 months (1-6 months after delivery). At each visit, two cervical specimens were taken, one for routine cytology and a second for HPV DNA hybridization using Virapap/Viratype, and a 5-ml blood sample was taken and a self-administered questionnaire was completed. RESULTS: In cervical specimens of the initial examination, HPV DNA was detected among 5.0% of pregnant and 5.2% of nonpregnant women, whereas HPV 16/18 was found in 80% of the HPV-positive specimens. Using multiple cervical specimens taken over time, 13.9% of the pregnant and 15.1% of the nonpregnant women tested positive for HPV DNA at least once. Adjusted for study group, age, and the number of available cervical specimens, ever detection of HPV infection (any type) was associated with more sexual partners and larger numbers of cigarettes smoked daily. An autoregressive generalized linear model was used to analyze the time-dependent multiple observations per study subject. Adjusting for age and trimester of pregnancy, the determinants of detecting high-risk HPV types (16/18 and 31/33/35) in the cervical specimen were an abnormal Pap smear, a positive HPV result in a preceding specimen, more than six sexual partners in the lifetime, and currently smoking more than 20 cigarettes per day with odds ratios of 10.9, 5.6, 3.2, and 2.7, respectively. CONCLUSION: Our data provide no evidence for a higher detection rate of HPV during pregnancy.

Adult↗

German family study on hereditary breast-ovarian cancer.

An estimated 5% to 10% of all breast and ovarian cancers are attributed to dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently identified. The involvement of these genes was studied in 43 German breast only and breast-ovarian cancer families. All families contained three or more cases of breast or ovarian cancer, with at least two diagnosed under the age of 60 years. Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus under the assumption of genetic heterogeneity, with an estimated 50% of families being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer families, the estimated proportions of linked families were 35% and 75%, respectively. Sixteen families with at least four cases of female breast cancer diagnosed under the age of 60 years, or male breast cancer diagnosed at any age, were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in six families.

Adult↗

Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea.

In this population-based study, we correlated possible risk factors for rodent-to-human transmission of Lassa virus with markers of Lassa fever in two different regions of the Republic of Guinea (Prefectures of Pita and Gueckedou). Antibody prevalence was 2.6% (6 of 232) in Pita compared with 14.0% (105 of 751) in Gueckedou, with up to 35.0% seropositivity in selected villages of the higher prevalence area. We observed three major risk factors in Gueckedou favoring Lassa virus transmission: rodent infestation was much higher, food was more often stored uncovered and most strikingly, peridomestic rodents were hunted as a protein source by 91.5% of the population as opposed to 0% in Pita. To control for the confounding effects of differences in rodent infestation and food storage, rodent consumption was analyzed as a risk factor for transmission of Lassa virus comparing rodent consumers (RC) and nonconsumers (NC) in Gueckedou only: 14.6% of RC had Lassa virus antibodies versus 7.4% of NC (P = 0.1) and 23.0% of RC reported a history of a febrile illness with hearing loss (the most common sequel of Lassa fever) versus 6.1% of NC (P = 0.003).

Adolescent↗

Prevalence of Helicobacter pylori infection and gastritis among young adults in China.

To investigate the prevalence of gastritis and H. pylori infection among young Chinese in Henan Province, a high incidence area for oesophageal cancer in China, the gastric mucosa was examined in 194 asymptomatic subjects, aged 15-26 years, in the course of an epidemiological study of precursor lesions of oesophageal cancer. Histopathological grading of gastritis and determination of H. pylori infection were performed on haematoxylineosin and Warthin-Starry stained section. An enzyme-linked immunosorbent assay was used to detect the presence of serum IgG antibodies to H. pylori. A very high prevalence of gastritis (93.8%) was found: 71 subjects (36.6%) presented with superficial gastritis (14 active), 94 (48.5%) with diffuse gastritis (92 active) and in 17 cases (8.8%) diffuse gastritis (16 active) was accompanied by focal atrophy. Silver staining detected H. pylori in 166 (85.6%) of the study participants. However, serological techniques identified H. pylori in only 109 (56.2%). H. pylori was seen in all the 119 cases showing histological signs of active gastritis, in 41 of the 63 cases (65%) without activity, and also in 50% (6/12) of histologically normal subjects. H. pylori infection was found to be associated with a 2.5-fold higher prevalence of chronic atrophic gastritis compared with non-atrophic gastritis. A family history of stomach cancer, consumption of pickled vegetables more than twice a month, and a high monthly salt consumption (> 500 g/month) also showed a positive association.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Risk assessment for familial occurrence of breast cancer].

There is now unequivocal evidence that an estimated 5% of breast cancer cases is inherited in families. Inherited predisposition of cancer in these families is thought to be the result of a mutation in one of several highly penetrant autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is localized on chromosome 17 q was recently isolated and at about the same time BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is also associated with predisposition to breast cancer but accounts for a very small proportion of inherited breast cancer. Many women want to know whether they have inherited a gene predisposing to breast cancer. Those with a family history of breast cancer are particularly concerned about their risk of disease. Currently the assessment of an individual's risk of breast cancer can be undertaken using prediction models based on family history and can be further refined when molecular genetic investigations became available. Without molecular characterisation the Claus tables derived from the Cancer and Steroid Hormone Study data set are best suited to predict breast cancer risk based on age of onset of affected relatives. Direct screening for mutations in breast cancer genes in not yet generally available. Testing for inherited susceptibility is currently being offered to selected families where multiple cases of breast and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as part of research protocols. In these families the so-called indirect gene analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of mutations with functional significance in the BRCA1 gene allows relatively refined risk assessment for non-diseased female family members. Some examples will be presented to illustrate risk assessment in different familial and individual situations. Risk assessment including test result interpretation and counselling can be appropriately provided directly to the patient by physicians and genetic counsellors in a coordinated genetic counselling setting.

Adult↗

Prevalence of transformation zone Chlamydia trachomatis DNA and serum antibodies in Tanzanian gynaecological in-patients.

Chlamydia trachomatis DNA was detected in cervical transformation zone swabs of gynaecological in-patients from Tanzania by two different polymerase chain reactions (PCR), one targetting the endogenous Chlamydia trachomatis plasmid (pCTT1) and the other a chlamydia genus specific rRNA gene. In only 7/131 (5.3%) cervical samples specific amplification products were obtained, in 6 cases with both PCRs, and in one with the plasmid-PCR alone. A 255 nt sequence was determined from the two plasmid-PCR fragments and revealed only one mismatch against the prototype sequence. Antibodies against genus specific chlamydia antigens were detectable by indirect immunofluorescence with titres > or = 1:256 in 29.0% (38/131) of all patients and in 50.0% (11/22) of patients with pelvic inflammatory disease (P = 0.17). No statistically significant association of either chlamydia antibodies or chlamydial DNA with any clinical condition was observable.

Adolescent↗

Familial risk and genetic susceptibility for breast cancer.

Clinical observations suggest that breast cancer is occasionally inherited as an autosomal dominant disease in families. Epidemiologic studies consistently have shown that a history of breast cancer in a first-degree relative increases a woman's risk of breast cancer when compared with the general population. The risk is similar if a mother or sister is affected and is increased further if both are affected. The difficulty with such an observation is that in itself it does not clarify the nature of the true underlying risk factors which could be genetic or due to the aggregation of environmental risk factors in families. Complex segregation analysis of breast cancer aggregation in families suggests that breast cancer susceptibility is due to an autosomal dominant inheritance of one or more rare genes in a few families in which carriers have a high probability of developing the disease perhaps as great as 100 percent. Close linkage of a breast-cancer-susceptibility gene (BRCA1), between markers of the chromosomal region 17q12-q21 on the long arm of chromosome 17, with breast cancer recently has been reported. Families linked to BRCA1 were more likely to have early onset of breast cancer or have breast and ovarian cancer in the family. It is likely that other genes play a role in the unlinked breast-cancer families. Both the epidemiologic and genetic data suggest that breast cancer is a heterogeneous disease.

Age of Onset↗

Vegetarian diets and colon cancer: the German experience.

The study assessed mortality and morbidity risks as related to nutritional status of moderate and strict vegetarians in Germany. The total cohort of 1904 self-identified persons was followed up for 11 y. Compared with national mortality rates for Federal Republic of Germany, the observed deaths for all causes were below expectation by a factor of 0.44 for men and 0.53 for women. The mortality for colon cancer was reduced [standardized mortality ration (SMR 44.1 for men and 77.9 for women]. No deaths were observed from rectal cancer. A vegetarian lifestyle of long duration (> or = 20 y) was associated with decreased overall and cancer mortality. Other determinants of decreased cause-specific mortality were physical activity, body weight, and strictness of adherence to the life-style. The relationship between a vegetarian and fiber-rich diet and a decreased risk for colon cancer has been reported in many studies. In this study, the influence of other factors such as health-conscious behavior and a healthy lifestyle seem to indicate partly stronger effects than nutrition itself. This may explain the generally better health of moderate vegetarians.

Cardiovascular Diseases↗

[The importance of genetic factors for development of breast cancer].

It is well documented that breast cancer aggregates in certain families suggesting a genetic etiology for this cancer. Numerous epidemiologic studies have shown that women with a first degree relative (mother, sister) with breast cancer have double the risk of developing this cancer when compared to women in the general population. More recent studies have shown that the magnitude of the risk of developing breast cancer is dependent on the age at diagnosis and the number of relatives affected. Aggregation of breast cancer in families in itself does not clarify the true nature of the underlying factors which could be genetic or due to familial resemblance in other risk factors. Complex segregation analyses of breast cancer families suggest that breast cancer susceptibility is inherited in some families as an autosomal dominant trait. Recently, a breast cancer susceptibility gene, BRCA1, has been mapped to chromosome 17q12-q21 through linkage analyses. BRCA1 appears to play a role in families with a large number of breast cancer cases who have developed breast cancer before the age 45, and/or who have breast and ovarian cancer cases. The risk of cancer for female carriers of the BRCA1 mutation has been estimated to be 87% for breast cancer and 44% for ovarian cancer by the age of 70. BRCA1 seems to play a role in only a proportion of affected families and it is likely that other genes are also involved. In the majority of breast cancer families with two or three cases, BRCA1 appears to play a small role.

Adult↗

Dietary and lifestyle determinants of mortality among German vegetarians.

Lifestyle characteristics of a cohort of 1904 Germans adhering mainly to a vegetarian diet were examined in relation to their mortality after 11 years of follow-up. Poisson regression modelling was performed to consider the simultaneous effects of different variables on mortality from all causes, cancer (ICD 140-208) and cardiovascular diseases (ICD 390-459). Compared to a low level of self-reported physical activity, those with a medium or high level of activity experienced only half the mortality from all causes and from cardiovascular diseases. Physical activity showed no beneficial effect for cancer mortality in this cohort. The body mass index (BMI) was an independent risk factor for mortality among men but essentially unrelated to mortality among women. Those in the middle third of the BMI distribution experienced the lowest mortality. A negative association between BMI and cancer mortality lost statistical significance when the first 5 years of follow-up were deleted, suggesting that a lower BMI was a consequence of prevalent disease. Both the duration of vegetarianism and the vegetarian status (strict versus moderate) showed a moderate effect on all cause and cancer mortality. A longer duration of vegetarianism (> or = 20 years) was associated with a lower risk, pointing to a real protective effect of this lifestyle. A lower risk of death among moderate vegetarians suggests that sound nutritional planning may be more important than absolute avoidance of meat.

Adolescent↗

[Etiology, pathogenesis and epidemiology or urothelial tumors].

A hospital-based case-control study of 531 male and 144 female matched pairs was conducted to analyse the role of nonoccupational and occupational risk factors in the etiology of tumors of the lower urinary tract. Smoking of cigarettes was associated with an increased risk and showed a significant dose- and time-response for both sexes. Heavy pipe smoking also significantly increased the risk. Controlling for smoking, a significantly twofold or more increase in risk was found for heavy consumption of coffee in both sexes and for heavy intake of beer in males. Increasing levels of total fluid intake were associated with increasing, smoking-adjusted risks in men. Significant associations were found for chronic infection of the lower urinary tract, familial history of bladder cancer, and frequent consumption of high fat meals among men and for frequent consumption of canned food in both sexes. With regard to occupational history, significantly elevated risks were found for ever-employment in the printing, plastics and synthetics, rubber, mining and dyestuffs industries, for exposure to spray paints, zinc, chromium/chromate, oils, petroleum and metal dust/fume, and for occupation as mining worker and truck driver among men. Multivariate logistic regression analysis showed-with the exception of fluid intake-significant contribution of the above-mentioned risks factors to the risk of bladder cancer.

Beer↗