Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene ( VDR ), rs1544410 ( Bsm I), and rs2228570 ( Fok I), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the Fok I ff genotype, which encodes a less transcriptionally active isoform of VDR , and reduced risk has been reported for the Bsm I BB genotype, a SNP in strong linkage disequilibrium with a 3′-untranslated region, which may influence VDR mRNA stability. Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. Results: The odds ratio (OR) for the rs2228570 ( Fok I) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 ( Bsm I) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297–305

Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study

Objective: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. Design: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. Results: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200ng/ml vs 200ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). Conclusion: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response

IGF-1, IGFBP-1, and IGFBP-3 Polymorphisms Predict Circulating IGF Levels but Not Breast Cancer Risk: Findings from the Breast and Prostate Cancer Cohort Consortium (BPC3)

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women

[Hormone replacement therapy in menopause and risk of breast cancer]

International audienceOBJECTIVES: Many epidemiological studies have analysed the relation between hormonal replacement therapy and risk of breast cancer. We present here a synthesis of the available results. MATERIAL AND METHODS: In 1997, a meta-analysis synthesised 90% of the data available at the time, obtained from 15 cohort and 36 case-control studies. This meta-analysis collected 53,000 breast cancers, 22% of these breast cancers having been observed in cohort studies. Since the publication of this meta-analysis, six studies totalling 8,000 cases (32% from cohort studies) have been published: two of these studies were partially included in the meta-analysis and the other four provided entirely new data. RESULTS: The conclusion, based on the available evidence, is that the risk of breast cancer diagnosis is higher among women who have used hormonal replacement therapy than among women who have not. The risk increases with treatment duration, is reduced when treatment is stopped and disappears almost completely a few years (5 in the meta-analysis) after the end of the treatment. The increase in the risk of breast cancer may be larger with estrogen-progestogen therapy than with estrogen alone. What are the consequences in terms of public health? From the results of the meta-analysis, one can estimate that the use of replacement therapy for 10 years between age 50 and 60 by 1,000 women will lead to the diagnosis of 6 extra breast cancers. This corresponds to the observation of 69 cases per 1,000 treated women after 20 years follow-up, as compared to the 63 cases expected among 1,000 untreated women. DISCUSSION: These results require confirmation. The observed increase in the risk of breast cancer is open to biases, particularly to a screening bias if women receiving hormonal replacement therapy have a more intensive surveillance than other women. Overall, the total number of women, across studies, who have received estrogen-progestogen therapy is small and their treatment was usually a combination of natural estrogens and medroxy progesterone acetate; therefore, the long term consequences of the treatments commonly used in France (synthetic estrogens and a variety of progestogens) have not been evaluated, this evaluation is much needed. CONCLUSION: What is needed is a global view of the risks and benefits of hormonal replacement therapy, and more epidemiologic data are required to reach this goal. In the present state of knowledge, the moderate excess risk of breast cancer observed does not justify a change in medical practice, neither in the selection of women to whom hormonal replacement therapy should be offered nor in the duration of their treatment

Un cas exceptionnel de Sarcoïdose multiviscérale

Cette thèse rapporte un cas de sarcoïdose sévère, suivi pendant 10 ans. A notre connaissance, aucun cas clinique n'a été décrit dans la littérature. Il s'agit d'une sarcoïdose multiviscérale, atteignant un nombre majeur de localisations (10 au total), dont certaines ont menacé le pronostic (atteinte neurologique et cardiaque), alors que certaines localisations dites " classiques " n'ont pas été observées comme les atteintes oculaire, articulaire, et la glandes exocrines. Au sein de chaque atteinte, certaines atypies ont été notées, telles que l'existence d'une atteinte péricardique sans atteinte myocardique, d'une atteinte pleurale alors que l'atteinte médiastino-pulmonaire est peu évolutive, d'une atteinte neurologique très polymorphe touchant l'ensemble des structures du système nerveux hormis les nerfs crâniens, alors que ceux-ci sont habituellement touchés chez les sujets de race noire. Une évolution particulièrement longue (10 ans), alors que la majorité des sarcoïdoses régresse spontanément en moins de 2 ans, est marquée par l'apparition successive de nouvelles localisations et de rechutes d'anciennes localisations malgré la corticothérapie, voire d'autres immunosuppresseurs. Une corticorésistance voire une " immunorésistance " imposant une escalade thérapeutique avec l'utilisation successive et associée de différents immunosuppresseurs. Toutes le atypies cliniques, radiologiques et évolutives ont conduit à une recherche permanente d'une autre pathologie ou de l'association de deux maladies, notamment c-tuberculose et sarcoïdose-lymphome.PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

[Development of a bio-library in the cohort survey: E3N-EPIC]

Since data from biological material banks are now considered as complementary to epidemiological data, most cohort studies have now integrated them. However, their constitution raises numerous logistical problems. The present paper describes the experience of investigators of an on-going prospective study in France: the E3N study. It reviews several constraints that this team had to face, E3N being a study with no individual benefit for the volunteers

[Development of a bio-library in the cohort survey: E3N-EPIC]

Since data from biological material banks are now considered as complementary to epidemiological data, most cohort studies have now integrated them. However, their constitution raises numerous logistical problems. The present paper describes the experience of investigators of an on-going prospective study in France: the E3N study. It reviews several constraints that this team had to face, E3N being a study with no individual benefit for the volunteers

[Hormone replacement therapy in menopause and risk of breast cancer]

Many studies have analysed the relation between hormone replacement therapy use and breast cancer risk. We performed a synthesis of their results based on a meta-analysis published in 1997, on fifteen observational studies published afterwards, and on a recent randomised trial. The accumulated evidence shows a higher risk of breast cancer among HRT ever users compared to non users. The risk increases with treatment duration and disappears a few years after the end of the treatment. Furthermore, recent observational studies showed that this risk may be higher when progestational agents are added to estrogens than when estrogens are used alone. This may be important in terms of public health since combination therapy with estrogen and progestational agents have become the standard of care among women with an intact uterus and are now commonly used. The effects of the treatments used in France, that are not those widely studied until now, must be evaluated, ideally through a randomized trial