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J Chang-Claude

Publications and source records attributed to J Chang-Claude.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inherited genetic susceptibility to breast cancer.

Inherited genetic susceptibility to breast cancer can be due both to genes which confer a high degree of risk and to polygenes which have a smaller effect on disease risk. An estimated 5-10% of breast cancer is considered to be due to mutations in genes conferring high risk which results in hereditary patterns of disease. Two major breast cancer susceptibility genes, BRCA1 and BRCA2, which were identified using linkage analysis in large extended breast and/or ovarian cancer pedigrees, are estimated to account for the majority of large families with breast/ovarian cancer predisposition and about two-thirds of large breast cancer families. The associated lifetime risk for breast cancer in mutation carriers ranges from 40% to 90%, depending on the extent of family history and the population. Other genetic factors, such as HRAS or CAG repeats of AR, as well as reproductive and hormonal factors may therefore modify cancer risk. Women at particularly high risk of developing breast cancer represent a group in whom expensive and rigorous screening programmes are cost-effective and who may benefit from trials of chemoprevention. There are only preliminary data on the efficacy of increased surveillance and on risk reduction due to prophylactic surgery. However, for chemoprevention to be equivalent to prophylactic mastectomy, it will be necessary to strive for an equivalent reduction. The efficacy of chemoprevention in this high-risk population is unknown. Existing and new agents for chemoprevention need to be carefully assessed in properly designed clinical trials among such women. In the process, other factors modifying the penetrance in mutation carriers need to be taken into account in order to evaluate the true effect of the chemopreventive agents. Polygenes confer much lower levels of risk and may be relevant for risk assessment when the effects of multiple loci, possibly in conjunction with environmental factors, are understood and quantified. At present, it seems unlikely that the genetic information at single polygenes will be clinically relevant for risk assessment and management.

Biomarkers, Tumor↗
PubMed2000

Absence of evidence for a familial breast cancer susceptibility gene at chromosome 8p12-p22.

Several recent studies indicate that the majority of families with five or fewer cases of breast cancer and no cases of ovarian cancer are not due to BRCA1 or BRCA2. It has been proposed that a further breast cancer susceptibility gene that may account for some of these families is located on chromosome 8p12-p22. We have identified 31 site-specific breast cancer families that have a greater than 80% posterior probability of being due to genes other than BRCA1 or BRCA2. These families have been examined for linkage to 8p12-p22 using markers flanking the putative location of the gene. The overall multi-point LOD score is strongly negative across the whole 44 cM. The individual multi-point LOD score is negative in 23 families and only exceeds 0.5 in a single family (with a multi-point LOD score of 1.22). The maximum heterogeneity LOD score was 0.03 at marker D8S136 with estimated proportion linked (alpha) of 3% (95% CI 0 - 30%). These data do not lend support to the hypothesis that chromosome 8p12-p22 harbours a familial breast cancer susceptibility gene. Oncogene (2000) 19, 4170 - 4173

BRCA2 Protein↗
PubMed2000

Progesterone receptor gene polymorphism is associated with decreased risk for breast cancer by age 50.

In a population-based case-control study for breast cancer before the age of 51 years, 554 cases and 559 age-matched controls were genotyped for the polymorphic progesterone receptor allele PROGINS. Breast cancer risk was decreased in women carrying the PROGINS allele. The odds ratio adjusted for age and study region was 0.76 [95% confidence interval (CI), 0.58-1.00]. Compared with wild-type A1/A1 homozygotes, the odds ratio for A1/A2 heterozygotes and A2/A2 homozygotes was 0.82 (95% CI, 0.62-1.08) and 0.27 (95% CI, 0.10-0.74), respectively, suggesting a gene dosage effect of the A2 allele. There was suggestive evidence for a differential effect by menopausal status (P = 0.07) and by family history of breast cancer (P = 0.15).

Adult↗
PubMed2000

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies.

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48-2.61) to 5.57 after 60 years (CI 4.18-7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 4.50 (CI 3.81-5. 33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1-4 years, OR = 0.65 (0. 53-0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0. 30-0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17-0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61-0.70) for all men and 0.73 (0.66-0.79) for men younger than 60. These estimates are higher than previously calculated.

Adult↗
PubMed2000

Breastfeeding and breast cancer risk by age 50 among women in Germany.

BACKGROUND: Epidemiological evidence which suggests that prolonged breastfeeding protects against breast cancer has accumulated in recent years. Issues with regard to the timing of breastfeeding and effect modification by correlates of breastfeeding and other risk factors of breast cancer remain unresolved. METHODS: A population-based case control family study of breast cancer among women diagnosed by the age of 50, conducted in two geographic areas in Germany, was used to evaluate the effect of breastfeeding on risk of breast cancer. RESULTS: Among parous women in this study (553 cases, 1094 age-matched population controls), having ever breastfed a child for at least 1 month did not confer protection (odds ratio of 0.9 and 95% confidence interval (CI) 0.8-1.2). However, risk of breast cancer significantly decreased with increasing duration of breastfeeding (p for trend = 0.01) and the estimated relative risk was 0.6 (95% CI 0.4-0.9) for 13-24 months of cumulative breastfeeding and 0.5 (95% CI 0.3-1.1) for 25 months or more. Risk was less related to number of children breastfed than to increasing average length of breastfeeding per child (p for trend = 0.03). CONCLUSIONS: The reduction in risk associated with duration of breastfeeding was not primarily due to breastfeeding the firstborn and more evident in women who were older (> 25 years) when they first breastfed and among women who experienced a recent full-term pregnancy. Risks were modified somewhat by a first-degree family history of breast cancer whereby a greater reduction in risk per additional month of breastfeeding was observed among women with a family history than those without (0.9 vs. 1.0). The study results support a protective role of prolonged breastfeeding against the development of breast cancer in predominantly premenopausal women in Germany.

Adult↗
PubMed2000

Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries.

BACKGROUND: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case-control studies. METHODS: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. RESULTS: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8-1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0-3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. CONCLUSION: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.

Bias↗
PubMed2000

A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability.

Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07-1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner.

Alleles↗
PubMed2000

Simultaneous interdisciplinary counseling in German breast/ovarian cancer families: first experiences with patient perceptions, surveillance behavior and acceptance of genetic testing.

As part of a multicenter study supported by the German Mildred Scheel foundation we have established an interdisciplinary counseling setting for members of breast and/or ovarian cancer families. We offer simultaneous counseling by a team consisting of a geneticist, a gynecologist and a psycho-oncologist. Here we describe our counseling protocol and our first short-term experience with this interdisciplinary approach. Preliminary data on patient perceptions and behaviors in the context of DNA testing are reported. Overall, our counseling approach was perceived as beneficial both by the counselors and the consultants. A marked overestimation of the risk to develop breast and/or ovarian cancer was noted in the group of unaffected individuals from medium to low risk breast cancer families in contrast to an appropriate risk perception in members from high risk families. All participants shared many of the same expectations about genetic testing and counseling and appeared to base their decision-making about testing on the risk classification given by the genetic counselor. The reported participation in gynecological cancer prevention programs was high in all families at risk, but was less sufficient in unaffected as compared to affected persons. Although current data on BRCA1/BRCA2 mutation analyses render testing in medium to low risk individuals questionable, our findings emphasize the importance of genetic counseling and education in all risk categories of breast and/or ovarian cancer families.

Adult↗
PubMed1999

Gender differences in the healthy worker effect among synthetic vitreous fiber workers.

The aim of this study was to determine whether the healthy worker effect and its component parts operate similarly for women and men. A cohort of workers from 14 synthetic vitreous fiber factories in seven countries, employed for at least 1 year between 1933 and 1977 and followed up to the early 1990s, included 375 deaths and 53,608 person-years among females and 2,568 deaths and 210,073 person-years among males. Standardized mortality ratios for all-cause and circulatory diseases were adjusted for country, age, calendar time, and gender. In addition, internal comparisons were adjusted for time since hire and employment status. The analyses addressed the following: 1) the healthy hire effect, 2) the time since hire effect, and 3) the healthy worker survivor effect. In this cohort, an overall healthy worker effect was not present in either gender. The healthy hire effect, based on standardized mortality ratios for years 1-4 since hire, was observed in males (standardized mortality ratio (SMR) = 0.8; 95% confidence interval (CI): 0.7, 1.0) but was less in females (SMR = 0.9; 95% CI: 0.5, 1.6). The relative risks increased slightly with time since hire in males but not in females. Higher mortality ratios were seen among those leaving employment than among those who remained actively employed; however, this effect was substantially greater for women (relative risk (RR) = 3.4; 95% CI: 1.8, 6.3) than men (RR = 1.8; 95% CI: 1.5, 2.1). The gender difference for active versus inactive status was stronger up to age 60 (men: RR = 1.7; 95% CI: 1.4, 2.0; women: RR = 3.6; 95% CI: 1.8, 7.1) than above that age. In conclusion, it appears that there is a stronger selection of healthy men than women into the workforce, while health-related selection out of the workforce is stronger for women than men.

Adult↗
PubMed1999

Tobacco, occupation and non-transitional-cell carcinoma of the bladder: an international case-control study.

Transitional-cell carcinoma is the dominant histological type of malignant tumors of the urinary bladder. There is limited information on risk factors for non-transitional-cell carcinoma (NTCC) of the bladder. We used data from 9 case-control studies on bladder cancer from 6 European countries to examine the association between NTCC, tobacco smoking and occupation. Information on 146 cases diagnosed with NTCC were matched by age, gender and study center to 727 non-cancer population or hospital controls and also with 722 transitional-cell-bladder-cancer controls. Lifetime smoking and occupational history were evaluated. A statistically significant excess risk for NTCC was observed for current smoking [odds ratio (OR) = 3.61, 95% confidence interval (CI) 2.08-6.28]. The risk increased with higher tobacco consumption (OR for highest tertile of pack-years = 7.01, 95% CI 3.60-13.66). The risks were higher for squamous-cell carcinomas than for other types of NTCC. Among major occupational groups, a significant excess risk was seen for field-crop and vegetable-farm workers (OR = 2.06, 95% CI 1.03-4.10). These results indicate that NTCC of the bladder is associated with smoking and specific occupations. The risk pattern seems to differ, in part, from that observed for transitional-cell carcinoma of the bladder.

Carcinoma, Squamous Cell↗
PubMed1999

Smoking as a confounder in case-control studies of occupational bladder cancer in women.

BACKGROUND: In studies in men, risk estimates on occupation and bladder cancer are distorted by about 10% when not adjusting for smoking. We examined the degree to which occupational risk estimates for bladder cancer in women are confounded by smoking, and the degree of residual confounding by inadequate control of this effect. METHODS: Primary data of 11 case-control studies on occupation and bladder cancer from Denmark, France, Germany, Greece, Italy, and Spain were pooled. Information for smoking and lifetime occupational history for 700 female cases and 2,425 female controls ages 30-79 was abstracted and recoded. Logistic regression was used to calculate odds ratios (OR) by occupation, applying five models which differed in their degree of adjustment for smoking. RESULTS: In major occupational groups, risk estimates were distorted by less than 10% when not adjusting for smoking. A statistically significant excess risk for bladder cancer was found in 13 specific occupations and industries. In most occupations, adjustment for smoking led the ORs towards the null value, but all statistically significant associations were maintained after adjustment. In three occupations (lathe operators, field crop workers, and wood manufacturers), a statistically significant excess risk was masked when not adjusting for smoking. In six occupations, estimates were distorted by more than 10% (-22% up to +40%). In occupations where smoking acted as a positive confounder, the proportion of confounding removed using a dichotomous smoking variable (ever/never) was around 60%. In one occupation (buyers), controlling for smoking status (ever, never) led to over-adjustment, because the percentage of smokers was high but the quantity smoked was low.

Adult↗
PubMed1999

Determination of the frequency of the common 657Del5 Nijmegen breakage syndrome mutation in the German population: no association with risk of breast cancer.

Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. It shares a number of features with the Ataxia telangiectasia (AT) syndrome: the most notable are high sensitivity to ionizing radiation and predisposition to cancer. Recently, the gene responsible for NBS has been identified on chromosome band 8q21. It encodes a DNA double-strand break repair protein, named Nibrin. A truncating 5-bp deletion (657Del5) has been identified in 90% of NBS patients and this is presumed to be of Slavic origin. There is evidence that heterozygous AT mutation carriers are predisposed to breast cancer. Since the NBS phenotype at the cellular level is very similar to AT, we have screened 477 German breast cancer patients, aged under 51 years, and 866 matched controls for the common NBS mutation. We have identified one carrier among the cases and one among the controls, indicating that the population frequency of this NBS mutation is 1 in 866 people (95% CI = 1 in 34,376 to 1 in 156) and the estimated prevalence of NBS is thus 1 in 3 million people. The proportion of breast cancer attributable to this mutation is less than 1%. Genes Chromosomes Cancer 25:393-395, 1999.

Breast Neoplasms↗
PubMed1999

Frequency of BRCA1 mutation 5382insC in German breast cancer patients.

OBJECTIVE: The aim of the study was to determine the frequency of the BRCA1 mutation 5382insC in German breast cancer patients with and without prior knowledge of a family history of breast cancer. METHODS: Two groups of breast cancer patients were tested for the presence or absence of the 5382insC mutation using a PCR primer mismatch assay. A sample of 248 patients unrelated by genealogy was selected based on a history of breast and/or ovarian cancer in the families. In addition, a population-based sample of 800 unselected breast cancer patients was included in the analysis. Three intragenic DNA markers D17S1323, D17S1322, and D17S855, located at BRCA1 introns 12, 19, and 20, respectively, were utilized for allelic association studies as well as for haplotype analysis in 4 breast/ovarian cancer families. RESULTS: The 5382insC mutation was identified in 10/248 (4.0%) familial breast cancer patients and in 8/800 (1.0%) unselected cases. Allelic association studies and haplotype analysis revealed an association of allele Nos. "6" at D17S1323 (chi2 value = 9.34, P = 0.007), "5" at D17S1322 (chi2 value = 3.62, P = 0.171), and "4" at D17S855 (chi2 value = 11.34, P = 0. 002) with the mutation 5382insC. CONCLUSION: 5382insC constitutes a frequent BRCA1 mutation in German breast cancer patients. The significant allelic association between this mutation and two intragenic DNA markers (D17S1323, D17S855) and the elevated allele frequency at marker D17S1322 suggest an ancient founder in the German breast cancer population. The PCR primer mismatch assay described herein provides a rapid and reliable detection method for the recurrent 5382insC mutation and will be useful for the analysis of large breast cancer populations.

Adult↗
PubMed1999

Occupation and bladder cancer in European women.

OBJECTIVES: We examined the importance of occupational exposures for bladder cancer in women. METHODS: We combined data from 11 case-control studies conducted between 1976 and 1996 in six European countries. The pooled data comprised 700 incident female cases and 2425 population or hospital controls, aged 30-79 years. Lifetime occupational and smoking history were examined using common coding. RESULTS: Excess risks were found in only a few of the occupations previously identified at high risk for bladder cancer. Statistically significant excess risks were observed for metal workers, particularly blacksmiths, toolmakers and machine tool operators (OR: 2.0, 95% CI: 1.1-3.6), tobacco workers (OR: 3.1, 95% CI: 1.1-9.3), field crop and vegetable farm workers (OR: 1.8, 95% CI: 1.0-3.1), tailors and dress makers (OR: 1.4, 95% CI: 1.0-2.1), saleswomen (OR: 2.6, 95% CI: 1.0-6.9), and mail sorting clerks (OR: 4.4, 95% CI: 1.0-19.5). About 8% (95% CI: 3.1 19.9) of all bladder cancers in women could be attributed to occupation after adjusting for smoking. The attributable risk was higher in women aged less than 65 years (12%), compared to older women (4%). CONCLUSIONS: The calculation of the attributable risk on the basis of results from this analysis may have caused some overestimation of the proportion of occupational bladder cancer in women. A significant proportion, however, of bladder cancer cases among European women less than 65 years is likely to be attributed to occupation. This link between bladder cancer in women and occupational factors has received little recognition, probably because studies addressing these issues have predominantly been done in men.

Adult↗
PubMed1999

Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies.

We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P<0.01). The lower mortality from ischemic heart disease among vegetarians was greater at younger ages and was restricted to those who had followed their current diet for >5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.

Adolescent↗