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Jenny Chang-Claude

Publications and source records attributed to Jenny Chang-Claude.

At least 19 recordsLinked to original sources
PubMed2026

Early and late CTCAE and patient-reported outcomes following lung cancer radiotherapy: A sex-stratified descriptive analysis from the REQUITE cohort.

BACKGROUND: Long-term prospective data on lung cancer patients treated with radiotherapy are limited, restricting understanding of outcomes and sex-specific characteristics. The multicentre REQUITE study provides standardized follow-up data from an international cohort. METHODS: We analysed longitudinal data from 530 lung cancer patients treated with radical radiotherapy (sequential or concurrent chemoradiotherapy, or stereotactic body radiation therapy [SBRT]) between 2014 and 2017 at 16 centres in Europe and the USA. Healthcare professionals prospectively recorded 21 pulmonary, oesophageal, neurological, cardiac, and skin adverse events using CTCAE v4.0. Patient-reported outcomes assessed symptoms, quality-of-life, fatigue, and physical activity. Adverse event incidence was stratified by sex, radiotherapy technique, chemotherapy administration, smoking status, and other clinical factors. RESULTS: At 12 months, 309 patients were evaluable, with 151 having follow-up beyond one year. Pulmonary adverse events were most frequent (40% grade ≥ 2), mainly dyspnoea and cough. Women had higher rates of oesophagitis, and more frequently reported dysphagia, and chest wall pain, while men experienced a higher frequency of cardiac adverse events. Exploratory subgroup analyses identified significant sex-related differences in grade ≥ 3 pulmonary adverse events following SBRT and in overall grade ≥ 2 oesophageal adverse events among patients with clinical stage I-II and those aged >70 years. Patient-reported outcomes showed persistent fatigue and reduced physical activity, particularly in females. Symptom prevalence and severity varied by sex, age, treatment modality, smoking status, and clinical stage. CONCLUSION: The REQUITE-Lung cohort provides prospectively collected real-world data on radiotherapy-related adverse events in lung cancer patients. This study describes patterns of adverse events and patient-reported outcomes according to sex, age, and treatment characteristics. These findings are hypothesis-generating and may support future validation in independent and pooled datasets.

Patient-reported outcomes↗
PubMed2026

Technical note: reconstructing dose distributions from manually planned electron boosts in breast radiotherapy.

PURPOSE: In breast radiotherapy, delivery of manually-calculated electron boosts limits retrospective dose-response analyses as dose distribution is unavailable. This work evaluates the feasibility of reconstructing dose distributions from manually planned electron boosts in breast-conserving radiotherapy. METHODS: Only 72 out of 198 breast cancer patients had complete stored dose distributions from sequential electron boosts in the REQUITE study. Arbitrary data from 70/72 patients were used to develop and validate dose reconstruction method. Twenty patients were used to determine optimal parameters for Monte-Carlo-based (MC) electron dose reconstruction on RayStation (v.11B-R), considering CT-calibration curve, MC-history number, andcalculation grid resolution. Remaining 50 patients were used to quantify dose reconstruction accuracy. The similarity between reconstructed and stored dose was evaluated using 3D-gamma index and dosimetric parameters extracted from breast and tumour bed contours. Dose difference location was evaluated using dose-location histogram. RESULTS: Calculation grid resolution significantly impacted electron dose distribution (p&#xa0;<&#xa0;0.01), where the finest grid (0.15&#xa0;cm) showed highest similarity to stored doses. CT-calibration curve and MC-history number had a negligible influence on dose reconstruction. Dosimetric difference between reconstructed and stored doses was&#xa0;<&#xa0;1&#xa0;Gy for breast and tumour bed. Reconstructed dose was achieved&#xa0;>&#xa0;90% gamma passing rate in the validation set. However, around 2.5&#xa0;Gy dose differences were observed at the skin and tissue interface regions. CONCLUSIONS: Retrospective electron boost dose reconstruction is feasible with acceptable accuracy, and could increase data completeness in large cohort studies. Caution is advised when assessing dose near tissue interface and further validation is needed outside the REQUITE dataset.

Electrons↗
PubMed2025

Genetic risk factors modulate the association between physical activity and colorectal cancer.

BACKGROUND: Physical activity (PA) is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene-PA interaction analysis. METHODS: Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (&#x2265; 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. RESULTS: PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81-0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA for CRC risk (p-interaction = 2.6&#xd7;10- 8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95%CI = 0.75-0.85), but no significant PA-CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5&#xd7;10- 8). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72-0.82). CONCLUSIONS: In summary, we identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis.

GWAS↗
PubMed2023

Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival.

Bovine milk and meat factors (BMMFs) are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co-markers and clinical parameters were not previously available and were therefore assessed in this study. Tissue sections with paired tumor-adjacent mucosa and tumor tissues of CRC patients [individual cohorts and tissue microarrays (TMAs) (n&#xa0;=&#x2009;246)], low-/high-grade dysplasia (LGD/HGD) and mucosa of healthy donors were used for immunohistochemical quantification of the expression of BMMF replication protein (Rep) and CD68/CD163 (macrophages) by co-immunofluorescence microscopy and immunohistochemical scoring (TMA). Rep was expressed in the tumor-adjacent mucosa of 99% of CRC patients (TMA), was histologically associated with CD68+/CD163+ macrophages and was increased in CRC patients when compared to healthy controls. Tumor tissues showed only low stromal Rep expression. Rep was expressed in LGD and less in HGD but was strongly expressed in LGD/HGD-adjacent tissues. Albeit not reaching statistical significance, incidence curves for CRC-specific death were increased for higher Rep expression (TMA), with high tumor-adjacent Rep expression being linked to the highest incidence of death. BMMF Rep expression might represent a marker and early risk factor for CRC. The correlation between Rep and CD68 expression supports a previous hypothesis that BMMF-specific inflammatory regulations, including macrophages, are involved in the pathogenesis of CRC.

Humans↗
PubMed2003

Analysis of pregnancy and other factors on detection of human papilloma virus (HPV) infection using weighted estimating equations for follow-up data.

Generalized estimating equations have been well established to draw inference for the marginal mean from follow-up data. Many studies suffer from missing data that may result in biased parameter estimates if the data are not missing completely at random. Robins and co-workers proposed using weighted estimating equations (WEE) in estimating the mean structure if drop-out occurs missing at random. We illustrate the differences between the WEE and the commonly applied available case analysis in a simulation study. We apply the WEE and reanalyse data of a longitudinal study of pregnancy and human papilloma virus (HPV) infection. We estimate the response probabilities and demonstrate that the data are not missing completely at random. Upon use of the WEE, we are able to show that pregnant women have an increased odds for an HPV infection compared with non-pregnant women after delivery (p=0.027). We conclude that the WEE are useful for dealing with monotone missing data due to drop-outs in follow-up data.

Cohort Studies↗
PubMed2003

A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer.

There is evidence that transforming growth factor (TGF)beta acts as a suppressor of tumor initiation but also as a promoter of tumor progression when the antiproliferative effect of the TGFbeta signaling pathway has been overridden by other oncogenic mutations. Several somatic mutations that disrupt the TGFbeta-SMAD signaling pathway have been reported in human breast tumors. We have examined the association between single nucleotide polymorphisms (SNPs) in the TGFbeta1 gene and the incidence of invasive breast cancer in three case-control series, with a maximum of 3987 patients and 3867 controls, median age approximately 50 years, and range 22-92 years. The promoter SNP, C-509T, and the T +29C signal-peptide SNP (encoding Leu10Pro) are in strong linkage disequilibrium. They are both significantly associated with increased incidence of invasive breast cancer in a recessive manner [odds ratios: (TT versus C-carrier), 1.25; 95% confidence intervals 1.06-1.48; P = 0.009 and (ProPro versus Leu-carrier), 1.21; 95% confidence intervals 1.05-1.37; P = 0.01]. The G-800A SNP was not significantly associated with incidence of breast cancer. The C-509T SNP is not contained within a known consensus sequence for a promoter regulatory element and therefore unlikely to affect TGFbeta1 expression, whereas the Leu10Pro signal peptide substitution potentially affects TGFbeta1 secretion. Transfections of HeLa cells with constructs encoding either the Pro or Leu forms of TGFbeta1 and driven by the cytomegalovirus promoter indicate that the signal peptide with Pro at residue 10 causes a 2.8-fold increase in secretion compared with the Leu form. These data indicate that the allele encoding Pro10 is associated with increased rates of TGFbeta1 secretion and with increased incidence of invasive breast cancer for the population samples described. It is estimated that 3% of all breast cancer cases may be attributable to Pro10 homozygosity.

Amino Acid Substitution↗
PubMed2003

Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy.

PURPOSE: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy. METHODS AND MATERIALS: Breast cancer patients receiving radiation therapy after a breast-conserving surgery were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryo-preserved lymphocytes from 113 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 26) of cells from a healthy donor. A coefficient of variation of 0.3 was calculated. RESULTS: The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Eleven patients were identified with considerably enhanced DNA damage induction, and 7 patients exhibited severely reduced DNA repair capacity after 15 and 30 min. Six patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of about 50 Gy. CONCLUSIONS: Using the alkaline comet assay as described here, breast cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin. Because impaired DNA repair could be involved in the development of late irradiation effects, individuals exhibiting severely reduced DNA repair capacity should be followed for the development of late clinical symptoms.

Acute Disease↗
PubMed2003

The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk.

The gene coding for the human homologue of the Drosophila segment polarity gene patched (PTCH1) is mutated in several common human tumors. In mice, haplodeficiency at the Ptch1 locus results in severe histologic defects in mammary ductal structure. We found no mutations within the coding region of PTCH1 in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls. We investigated whether this variant influences susceptibility for breast cancer in 611 breast cancer patients diagnosed by age 50 years and 1,057 controls matched by age and study region in Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and genotype frequencies were not different between cases and controls. However, multivariate logistic regression analysis revealed an effect modification of oral contraceptive use (OC) on breast cancer risk by Leu-carrier status. Compared to women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu-carriers who never used OC, but this was attenuated among Leu-carriers who ever used OC by 20%. The gene-environmental interaction was confirmed in case-only analysis of the German and British studies, yielding an interaction odds ratio of 0.7 for premenopausal women (p = 0.06). Longer duration of pill use was associated with a significantly greater risk reduction (p for trend = 0.015). Our novel observation of a differential effect of OC use on breast cancer risk by PTCH1 1315Leu-carrier status suggests the interesting possibility of the Sonic hedgehog/Patched (SHH/PTCH1) signaling pathway being involved in hormone-induced development of breast carcinoma.

Adult↗
PubMed2003

Case-control study of physical activity and breast cancer risk among premenopausal women in Germany.

Important aspects of the recognized inverse relation between physical activity and breast cancer risk are still under discussion. Data on physical activity from sports, occupational activity, household tasks, walking, and cycling by reported frequency, duration, and intensity during adolescence and young adulthood were collected in 1999-2000 from 360 premenopausal breast cancer cases and 886 controls who had previously participated in a German population-based case-control study. In multivariate conditional logistic regression, no association between total physical activity and premenopausal breast cancer was found in two age periods. For women who were active during both periods, the adjusted odds ratio was 0.83 (95% confidence interval: 0.60, 1.14). When both age periods were combined, higher quartiles of total physical activity compared with the lowest quartile showed adjusted odds ratios of 0.97, 0.68, and 0.94. Only the effect of moderately high physical activity was statistically significant. Analyses by type of activity revealed significant protective effects for women who reported the highest levels of cycling activities (adjusted odds ratio = 0.66, 95% confidence interval: 0.45, 0.97). These data do not suggest an inverse monotonic association between total physical activity and breast cancer risk in premenopausal women. The study prevalence of cycling and walking for transportation demonstrated that national habits need consideration in the exposure assessment.

Adolescent↗
PubMed2003

Haplotype sharing analysis with SNPs in candidate genes: the Genetic Analysis Workshop 12 example.

Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on affection and harbors more than 70 SNPs. Haplotype sharing analysis depends heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong evidence was found for most SNPs in the isolated population sample, thus providing evidence for an involvement of this gene, but the maximum -log(10)(p) values for the haplotype sharing statistics (HSS) test statistic did not correspond to the location of the true variant in either population. In comparison, transmission disequilibrium test (TDT) analysis showed the strongest results at the disease-causing variant in both populations, and these were outstanding in the general population. In this example, TDT analysis appears to perform better than HSS in identifying the disease-causing variant, using SNPs within a candidate gene in an outbred population. Simulations showed that the performance of HSS is hampered by closely spaced SNPs in strong linkage disequilibrium with the functional variant and by ambiguous haplotypes.

Chromosome Mapping↗
PubMed2003

Reproductive factors and familial predisposition for breast cancer by age 50 years. A case-control-family study for assessing main effects and possible gene-environment interaction.

BACKGROUND: The effect of environmental/lifestyle factors on breast cancer risk may be modified by genetic predisposition. METHODS: In a population-based case-control-family study performed in Germany including 706 cases by age 50 years, 1381 population, and 252 sister controls, we investigated main effects for environmental/lifestyle factors and genetic susceptibility and gene-environment interaction (G x E). Different surrogate measures for genetic predisposition using pedigree information were used: first-degree family history of breast or ovarian cancer; and gene carrier probability using a genetic model based on rare dominant genes. Possible G x E interaction was studied by (1) logistic regression using cases and population controls including an interaction term; (2) comparing results using sister controls and population controls; (3) case-only analysis with logistic regression and (4) a mixture logistic model. RESULTS: Familial predisposition showed the strongest main effect and the estimated gene carrier probability gave the best fit. High parity and longer duration of breastfeeding reduced breast cancer risk significantly, a history of abortions increased risk and age at menarche showed no significant effect. We found significant G x E interaction between parity and genetic susceptibility using different surrogate measures. In women most likely to have a high genetic susceptibility, high parity was less protective. Later age at menarche was protective in women with a positive family history. No evidence for G x E interaction was found for breastfeeding and abortion. CONCLUSIONS: These findings corroborate results from other studies and provide further evidence that the magnitude of protection from parity is reduced in women most likely to have a genetic risk in spite of the limitations of using surrogate genetic measures.

Abortion, Therapeutic↗
PubMed2002

Active and passive smoking and risk of breast cancer by age 50 years among German women.

Recent studies suggest that both active and passive smokers have an increased risk of breast cancer compared with women who have never been either actively or passively exposed. Data on lifetime active and passive smoking were collected in 1999-2000 from 468 predominantly premenopausal breast cancer patients diagnosed by age 50 years and 1,093 controls who had previously participated in a German case-control study conducted in 1992-1995. Compared with never active/passive smokers, former smokers and current smokers had odds ratios of 1.2 (95% confidence interval (CI): 0.8, 1.7) and 1.5 (95% CI: 1.0, 2.2), respectively, and ever active smokers had an odds ratio of 1.3 (95% CI: 0.9, 1.9). The risk increased with duration of smoking and decreased after cessation of smoking. Among never active smokers, ever passive smoking was associated with an odds ratio of 1.6 (95% CI: 1.1, 2.4). Exposure to environmental tobacco smoke during childhood or before the first pregnancy did not appear to increase breast cancer risk. At greatest risk were women who had a high level of exposure to both passive and active smoking (odds ratio = 1.8, 95% CI: 1.2, 2.7). This study strengthens the hypothesis of a causal relation between active and passive smoke exposures and breast cancer risk.

Adult↗
PubMed2002

Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations.

Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.

Breast Neoplasms↗
PubMed2002

Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium.

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (alpha) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (alpha = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at alpha = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

Australia↗
PubMed2002

Studies on radiosensitivity from an epidemiological point of view - overview of methods and results.

BACKGROUND AND PURPOSE: The establishment of a predictive in vitro assay for radiosensitivity has been a goal in radiotherapy research. To date, no single assay has proven to be effective for this purpose. A review of the epidemiologic methods used in the studies has been undertaken to evaluate limitations associated with specific design options and to develop recommendations for future research. MATERIALS AND METHODS: We focused on studies attempting to establish the usefulness of an assay in breast cancer patients undergoing radiotherapy using skin reactions as indicators for radiosensitivity. The 25 published studies included were evaluated with respect to criteria for good epidemiological studies: (a) study design, (b) study population, (c) assessment of radiation reaction, and (d) treatment of confounding factors. RESULTS: Limitations in study design were often found among the studies reviewed. Possible sources of bias are, among others, misclassification due to non-standardized assessment of side effects, selection bias due to drawing convenience patient groups instead of representative patient groups, and confounding due to analysis not adjusted for important factors influencing the severity of side effects. CONCLUSIONS: Further studies should make use of good epidemiological practice so that valid conclusions can be drawn with respect to the usefulness of an in vitro assay to distinguish between patients with different degrees of radiosensitivity in clinical practice.

Breast Neoplasms↗
PubMed2002

Lung cancer among rock and slag wool production workers.

BACKGROUND: Previous cohort studies have found an elevated risk of lung cancer among rock and slag wool (RSW) production workers. The aim of the present study was to investigate the risk of lung cancer associated with exposure to RSW while controlling for other occupational exposures and tobacco smoking. METHODS: Since 1971, a total of 196 lung cancer cases occurred among men who worked in seven plants in Denmark, Norway, Sweden, and Germany, with start of production between 1937 and 1950. We obtained information on occupational history and extra-occupational factors from either the subject or the next of kin for 133 cases and 513 matched controls. We assessed occupational exposure on the basis of interview data combined with information from expert panels set up in each factory. RESULTS: For cumulative exposure to RSW assessed with a 15-year lag, the smoking-adjusted odds ratios in the second, third, and fourth quartiles of exposure were 1.3 (95% confidence interval [CI] = 0.7-2.3), 1.0 (CI = 0.5-1.9), and 0.7 (CI = 0.3-1.3). Similar results were obtained when we included only those workers employed for more than 1 year, when we included other indicators of RSW exposure, and after control for co-exposures. CONCLUSIONS: This study provides no evidence of a carcinogenic effect on the lung of rock and slag wool under exposure circumstances in the production industry during the last four to five decades.

Adult↗
PubMed2002

Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years.

We used a large population-based case-control study to determine whether three known p53 polymorphisms, intron 3 16 bp duplication, codon 72(Arg/Pro) and intron 6 MspI restriction fragment length polymorphism, alter the risk for breast cancer in German women. For all three polymorphisms, the odds ratios (ORs) for breast cancer were increased in women carrying the rare allele; however, this was statistically significant only for the 16 bp duplication polymorphism. Compared with the 16 bp duplication wild-type A1/A1 genotype, ORs for A1/A2 genotype and A2/A2 genotype were 1.3 [95% confidence interval (CI) 1.0-1.7] and 1.7 (95% CI 0.8-3.4), suggesting an allele dosage effect (trend test, P = 0.03). Significant evidence was found for a differential effect by family history of breast cancer (P = 0.03 for interaction), with the OR being 5.3 among women with a first degree family history. Our data suggest that inheritance of an intronic polymorphism in the p53 gene increases breast cancer risk appreciably in women by the age of 50 years with a family history of breast cancer in the German population.

Breast Neoplasms↗