Risk Of Female Breast Cancer Research Articles

Obesity, diabetes mellitus, and the risk of female breast cancer in Eastern China

BackgroundThis study was designed to explore the relationship between obesity, diabetes mellitus (DM), and female breast cancer in Eastern China.MethodsA 1:3 matched case–control study was carried out, comprising 123 women with breast cancer and 369 controls. All of the 492 subjects were selected from a previous epidemiological survey of 122,058 women in Eastern China.ResultsThere were significant differences between the case and control groups in waist circumference and body mass index (BMI), but not in waist to hip ratio or hip circumference. There was a significant difference between the two groups in BMI for post-menopausal women, and a significant difference in waist circumference for pre-menopausal women. After adjustment for other factors, BMI was still significantly associated with breast cancer (odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.14 to 2.19). DM was significantly associated with breast cancer (OR = 3.35, 95% CI 1.02 to 11.01) in the univariate analysis but not in the multivariate analysis (P = 0.059).ConclusionsObesity might be a risk factor for female breast cancer. We found different strengths of association for women with different menopausal status when we examined the relationship between obesity and breast cancer. The association between DM and female breast cancer should be further confirmed with larger sample sizes.

The clinical consequences of hemizygosity across 2 MB of 10q23 are restricted to Cowden syndrome

Cowden syndrome is caused by germline mutations in PTEN and clinically characterized by hamartomas, macrocephaly, classic dermatologic stigmata, and an estimated 85 % lifetime risk of female breast cancer. A young woman with macrocephaly, tricholemmomas, AV malformations, and mammary papillomatosis was found to be hemizygous for PTEN in her germline DNA. Using MLPA, comparative genomic hybridization, and DNA sequencing, we identified a 2-Mb deletion in chromosome 10 spanning 344-kb centromeric and 1.7-Mb telomeric of PTEN. Her father who has a clinical history including macrocephaly, Hashimoto's thyroiditis, colonic polyposis, acral keratoses, and goiter was also found to have the same deletion. In benign breast tissue from the hemizygous female, PTEN protein expression was significantly reduced in luminal and stromal cells but present in the myoepithelium. Compared with a typical papilloma of the breast which had intense cytoplasmic PTEN staining, the majority of the patient's papilloma had significantly decreased PTEN expression while some cells had mislocalized perinuclear PTEN expression. In addition to PTEN, 22 other protein-coding genes were deleted including two predicted haploinsufficient genes and five additional genes that have previously been associated with hereditary predispositions to certain diseases. However, because all significant clinical features of the proband and her father are common to patients with genetic alterations in PTEN, the other 22 hemizygous protein-coding genes appear to be haplosufficient.

Light Deficiency Confers Breast Cancer Risk by Endocrine Disorders

North-America and northern European countries exhibit the highest incidence rate of breast cancer, whereas women in southern regions are relatively protected. Immigrants from low cancer incidence regions to high-incidence areas might exhibit similarly higher or excessive cancer risk as compared with the inhabitants of their adoptive country. Additional cancer risk may be conferred by incongruence between their biological characteristics and foreign environment. Many studies established the racial/ethnic disparities in the risk and nature of female breast cancer in United States between African-American and Caucasian women. Mammary tumors in black women are diagnosed at earlier age, and are associated with higher rate of mortality as compared with cancers of white cases. Results of studies on these ethnic/racial differences in breast cancer incidence suggest that excessive pigmentation of dark skinned women results in a relative light-deficiency. Poor light exposure may explain the deleterious metabolic and hormonal alterations; such as insulin resistance, deficiencies of estrogen, thyroxin and vitamin-D conferring excessive cancer risk. The more northern the location of an adoptive country the higher the cancer risk for dark skinned immigrants. Recognition of the deleterious systemic effects of darkness and excessive melatonin synthesis enables cancer protection treatment for people living in light-deficient environment. Recent patents provide new methods for the prevention of hormonal and metabolic abnormities.

Catechol-O-methyltransferase Val 108/158 Met polymorphism and breast cancer risk: a case control study in Syria

Catechol-O-methyltransferase (COMT) inactivates catechol estrogens by methylation and thus may play a protective role against mutations induced by estrogen metabolites. In this study we investigated the relationship between the Vall58Met polymorphism in the COMT gene and breast cancer risk in a population-based case control study in Syria. We examined 135 breast cancer patients and 107 healthy controls in North Syria to determine the association between the functional genetic Val158Met polymorphism in the COMT gene and female breast cancer risk. There was no significant overall association between the COMT genotype and individual susceptibility to breast cancer. Our data suggest that there may be no overall association between the COMT genotype and breast cancer.

Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR) = 1.30, p = 7.98×10−4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10−6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs—rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)—showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.

Non-daytime work and risk of cancers of the breast, prostate, colo-rectum, endometrium, and skin, and non-Hodgkin lymphoma in the Nordic countries – the NOCCA study

ObjectivesDuring the last decade, growing evidence has been provided that non-day time work (“shiftwork”) may increase the risk of female breast cancer. It has also been suggested that shiftwork may...

Abstract 3733: A meta-analysis of diet, physical activity and breast cancer risk: An evolutionary perspective

Abstract The human genome was adapted to an environment different from that experienced by modern industrialized humans. The reconstruction of lifestyle, reproductive and dietary characteristics of human ancestors is therefore important in understanding breast cancer. Moreover, cultural evolution occurs at a faster rate than genetic adaptation, resulting in evolutionary discordance between modern human genes and lifestyle. This mismatch between genetic biology and modern lifestyle factors may foster the development and propagation of breast cancer because of potential impact on circulating hormones and body mass. Diet and exercise may differentially affect breast cancer risk during reproductive and menopausal years. This study examines evolutionary discordance in energy consumption, expenditure and reproductive events as it relates to risk of female breast cancer. Published literature evaluating relationships between breast cancer risk and dietary fat, and exercise was systematically reviewed up to May of 2010. Descriptive data, estimates of relative risk and 95% confidence interval (CI) were extracted from relative studies, sorted according to inclusion criteria and analyzed using the random effects model of DerSimonian and Laird. The results reveal disparity between exercise load, fat intake, study type and reproductive status. Cohort study results indicated significant summary relative risks between poly-unsaturated fat and breast cancer (1.091, 95% CI: 1.001; 1.184). In case-control studies no association between fat and breast cancer was observed. Reproductive status influenced the affect of dietary fat on breast cancer risk. Post-menopausal women exhibited a significant association between total fat (1.042, 95%CI: 1.013; 1.073), poly-unsaturated fat intake (1.22, 95% CI: 1.08; 1.381) and breast cancer. A non-significant inverse relationship between fat types and breast cancer was identified in premenopausal women. Evidence for significant inverse relationships between exercise and breast cancer were observed in all categories. In sum: a. Higher levels of exercise could decrease breast cancer risk b. Higher consumption of dietary fat may increase breast cancer risk c. Reproductive status may influence breast cancer risk in women These results have important implications for future breast cancer research. Interactions between modern cultural factors and ancestral biology may be expressed as higher rates of breast cancers in modern, industrialized nations. Clinical studies do not cumulatively examine population variations in socio-economic, cultural and biological risk factors and breast cancer occurrence. Applying an anthropological and biocultural perspective to future research could identify evolutionary roots to causes and risk factors of female reproductive diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2011-3733

Abstract 1108: Ferritin binds breast cancer cells and tissue, and promotes proliferation independently of iron content

Abstract A connection between iron and breast tumorigenesis has been convincingly argued over the years. Several in vivo studies have demonstrated that iron-rich diets increase tumor incidence rate in carcinogen-induced mammary tumor models. Moreover, a large cohort study has recently associated mutations in the hemochromatosis (HFE) gene (promoting iron overload) with breast cancer risk in females. Individuals with mutations in the HFE protein can exhibit iron accumulation in the liver, high transferrin saturation levels, and elevated serum ferritin levels, but not have clinical hemochromatosis. Cells store iron in ferritin, but this protein is also secreted and is detected circulating in serum. Although serum ferritin has been used as an indicator of total body iron, a specific functional role has not been proposed thus far other than perhaps recycling iron to the bone marrow. Interestingly, serum ferritin levels have been shown to be increased in breast cancer patients, and higher levels seem to be associated with poorer prognosis. Furthermore, comparisons between pre- and post-surgery ferritin levels suggested that the tumor itself is responsible for the high levels of serum ferritin possibly through secretion. We have demonstrated that ferritin binds to breast tumor sections obtained from biopsy. Based on these observations, we hypothesized that serum ferritin interacts directly with breast cancer cells enhancing their growth. In this study we report that ferritin exposure will increase proliferation and DNA synthesis in the breast cancer cell lines, MCF-7 and T47D. These effects were not dependent on the iron content of ferritin, as both apo- and holo-ferritin had comparable effects. Because extra-cellular ferritin has been speculated to play an iron delivery role in some cells, we examined changes in transferrin receptor levels, and the quenching of the fluorescent metal-sensitive dye calcein following ferritin treatments. Our data, suggests that ferritin does not deliver iron to cells, and might have an iron-independent signaling function. Taken together, these findings encourage a new perspective on serum ferritin in cancer biology, and raise several possibilities for novel therapeutic and diagnostic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1108. doi:10.1158/1538-7445.AM2011-1108

Abstract 835: Elevated in utero estrogenic environment may increase later breast cancer risk by down-regulating miRNAs

Abstract Objectives: High maternal estrogen levels during pregnancy increase a female offspring's breast cancer risk in women and in animal models. This increase is proposed to be mediated by epigenetic changes that involve DNA methylation. Dynamic changes in miRNA expression during fetal development also play a key role in setting gene transcription patterns that persist through the life-time. In this study, we investigated whether in utero exposure to excess estradiol (E2) causes persistent changes in the expression of miRNAs and their target genes. Methods: Pregnant Sprague Dawley rats were fed AIN93G diet supplemented with 0.1 ppm ethinyl estradiol between gestation days 13 and 20. Offspring's mammary glands were obtained on postnatal day 50, and miRNAs were measured using applied Biosystems TaqManR Array Rodent MicroRNA and mRNAs using RG_U34A Affymetrix platform. Data generated in the two arrays were analyzed by an integrated approach which uses a sequence-based TargetScan method to predict miRNA targets and then correlates these targets with mRNA data to identify targets specific to in utero E2 exposure. Results: Maternal E2 exposure during pregnancy increases carcinogen-induced mammary tumorigenesis in the offspring (final tumor incidence in controls: 56%, in E2 offspring: 82%, p&amp;lt;0.05). Fifteen miRNAs are significantly down-regulated in the mammary glands of adult rats exposed to E2 in utero, compared to the controls. Many of these are known to be down-regulated by E2 in MCF-7 human breast cancer cells including miR-21, miR-23ab, miR-27ab, and miR-200c. Some of these miRNAs and others that are down-regulated in the mammary glands of in utero E2 exposed rats (let-7, miR-26ab, miR-181, and miR-203), in turn, suppress the expression of estradiol-regulated genes, as defined by Cicatiello et al., 2010. We also found that of the known ER-α activated genes, more than 10% are significantly up-regulated in the E2 group. These genes included BCL2L1, CYP1B1, and IGF1R. Conclusions: Our findings indicate that maternal exposure to excess E2 during pregnancy may cause a persistent up-regulation of estrogen-regulated genes by suppressing miRNAs that target these genes. Of note is that some of the miRNAs found to be down-regulated in the E2 group suppress genes known to be involved in DNA methylation. For example, miR-21 targets DNMT1; our study indicates that mammary glands of rats exposed to excess E2 in utero express significantly elevated DNMT1 levels, compared to the controls. Thus, changes in miRNAs may also be involved in inducing DNA methylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 835. doi:10.1158/1538-7445.AM2011-835

PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China

The programmed death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. In order to investigate the association between polymorphisms of PD-1 and breast cancer, a case-control study was conducted in Chinese female population consisting of 490 cases with breast cancer and 512 age-matched healthy individuals from Heilongjiang Province of China. Four polymorphisms of the PD-1 gene, including rs36084323 (PD-1.1), rs7421861, rs2227982 (PD-1.9), and rs2227981 (PD-1.5), were selected and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of PD-1.1 GG genotype and PD-1.5 CT genotype were significantly lower in cases compared with controls (P = 0.020 and 0.004, respectively), and PD-1.5 CC genotype and C allele had higher frequencies in cases (P = 0.003 and 0.010). In haplotype analysis, we observed that the frequencies of ATTC and GTCT haplotypes were lower in cases than those of in controls (P = 0.0055 and 0.0012, respectively), whereas the GTCC and ATCC haplotypes had higher frequencies in cases (P = 0.0040 and 0.00008037, respectively). Additionally, strong association was showed between PD-1.1 and P53, and haplotype CCTA was associated with ER status. These results primarily suggest that PD-1 gene polymorphisms may affect the breast cancer risk and prognosis in Chinese Han females of Heilongjiang Province in Northeast China.

Association of L55M and Q192R polymorphisms in paraoxonase 1 (PON1) gene with breast cancer risk and their clinical significance

The HDL-associated paraoxonase (PON) activities play a role in decreasing oxidative stress, which is known to contribute to cancer development. The aim of this study was to examine the relation between the PON1 L55M and Q192R polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinicopathological parameters of BC. Both polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, using DNA from peripheral blood in a case control study. With respect to PON1 L55M, the mutated allele (M) frequency was found in 70.5% in BC patients and in 53.5% in controls; the M allele was significantly associated with an increased risk of BC (adjusted odds ratio (OR(adj)) 2.07, 95% confidence interval (95% CI) 1.37-3.13; P=0.011). The homozygous mutant genotype (MM) significantly increased the risk of BC (OR(adj) 2.07, 95% CI 1.17-3.64, P=0.011). However, as regard PON1 Q192R, the R mutated allele frequency was found in 28.5% in BC patients and in 33% in controls, the women who were QR heterozygotes (OR(adj) 0.96, 95% CI 0.55-1.68) or RR homozygotes (OR(adj) 0.64, 95% CI 0.25-1.63), and R allele (OR(adj) 0.81, 95% CI 0.53-1.42) did not show any risk for BC. Both PON1 L55M and Q192R polymorphisms genotype frequencies were not related to patient's age (P=0.94 and 0.72, respectively). M allele genotypes (LM/MM) carriers showed significant association only with nodal metastases (P=0.02) but not with other clinicopathologic parameters. However, R allele genotype (QR/RR) carriers showed insignificant correlation with clinicopathological parameters. In conclusion, our results suggest that the M allele of L55M polymorphism could be a suitable marker for BC susceptibility and tumor prognosis in Egyptian women.

Adenoid cystic carcinoma of the breast in the United States (1977 to 2006): a population-based cohort study

IntroductionAdenoid cystic carcinoma of the breast (breast-ACC) is a rare and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC incidence, relative survival, and associated cancer risk in the United States.MethodsUsing data from the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), and relative survival for breast-ACC, and standardized incidence ratios (SIRs) for other cancers.ResultsOverall 338 women (IR = 0.92/1 million person-years) were diagnosed with breast-ACC during 1977 to 2006. Blacks had 39% lower IRs than Whites (IRR = 0.61, 95% confidence interval = 0.37 to 0.96), and IRs remained constant over the 30-year period. Ninety-five percent of cases presented with localized stage (n = 320; IR = 0.87), and the highest IRs were observed for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative tumors (IR = 0.56). Like other typically ER-negative tumors, age-specific IRs increased until midlife and then plateaued. Five-year, 10-year, and 15-year relative survival was 98.1%, 94.9%, and 91.4%, respectively. The risk of female breast cancer was not increased following (SIR = 0.89, 95% confidence interval = 0.43 to 1.64) or preceding (SIR = 0.71, 95% confidence interval = 0.28 to 1.46) breast-ACC. Similarly, no association was observed for breast-ACC and risk of all other cancers combined, solid tumors, or lymphohematopoietic malignancies.ConclusionsBreast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and lend credence to the apparent heterogeneity of basal-like breast cancers.

Extremely low-frequency electromagnetic fields exposure and female breast cancer risk: a meta-analysis based on 24,338 cases and 60,628 controls

Exposure to extremely low-frequency electromagnetic fields (ELF-EMF) has been suggested to increase female breast cancer risk; however, the data have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, the Cochrane Library and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between ELF-EMF exposure and female breast cancer risk. A total of 15 studies published over the period 2000 to 2009 including 24,338 cases and 60,628 controls were involved in this meta-analysis. The results showed no significant association between ELF-EMF exposure and female breast cancer risk in total analysis (OR = 0.988, 95% CI = 0.898-1.088) and in all the subgroup analyses by exposure modes, menopausal status, and estrogen receptor status. This result is in accordance with the previous meta-analysis carried out by Erren in 2000. In conclusion, this meta-analysis suggests that ELF-EMF exposure has no association with the susceptibility of female breast cancer.

The challenge of AIDS-related malignancies in sub-Saharan Africa.

BackgroundWith the lengthening of life expectancy among HIV-positive subjects related to the use of highly active antiretroviral treatments, an increased risk of cancer has been described in industrialized countries. The question is to determine what occurs now and will happen in the future in the low income countries and particularly in sub-Saharan Africa where more than two-thirds of all HIV-positive people live in the world. The objective of our paper is to review the link between HIV and cancer in sub-Saharan Africa, putting it in perspective with what is already known in Western countries.Methods and FindingsStudies for this review were identified from several bibliographical databases including Pubmed, Scopus, Cochrane, Pascal, Web of Science and using keywords “HIV, neoplasia, epidemiology and Africa” and related MesH terms. A clear association was found between HIV infection and AIDS-classifying cancers. In case-referent studies, odds ratios (OR) were ranging from 21.9 (95% Confidence Interval (CI) 12.5–38.6) to 47.1 (31.9–69.8) for Kaposi sarcoma and from 5.0 (2.7–9.5) to 12.6 (2.2–54.4) for non Hodgkin lymphoma. The association was less strong for invasive cervical cancer with ORs ranging from 1.1 (0.7–1.2) to 1.6 (1.1–2.3), whereas ORs for squamous intraepithelial lesions were higher, from 4.4 (2.3–8.4) to 17.0 (2.2–134.1). For non AIDS-classifying cancers, squamous cell conjunctival carcinoma of the eye was associated with HIV in many case-referent studies with ORs from 2.6 (1.4–4.9) to 13.0 (4.5–39.4). A record-linkage study conducted in Uganda showed an association between Hodgkin lymphoma and HIV infection with a standardized incidence ratio of 5.7 (1.2–17) although OR in case-referent studies ranged from 1.4 (0.7–2.8) to 1.6 (1.0–2.7). Other cancer sites found positively associated with HIV include lung, liver, anus, penis, vulva, kidney, thyroid and uterus and a decreased risk of female breast cancer. These results so far based on a relatively small number of studies warrant further epidemiological investigations, taking into account other known risk factors for these tumors.ConclusionStudies conducted in sub-Saharan Africa show that HIV infection is not only strongly associated with AIDS-classifying cancers but also provided some evidence of association for other neoplasia. African countries need now to implement well designed population-based studies in order to better describe the spectrum of AIDS-associated malignancies and the most effective strategies for their prevention, screening and treatment.

Synergistic Effects of Polymorphisms in DNA Repair Genes and Endogenous Estrogen Exposure on Female Breast Cancer Risk

Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damage by means of repair enzymes. Genotypic variants of DNA damage repair genes, participating in base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. In a hospital-based case-control study of female breast cancer, DNA samples were obtained from 401 cases and 533 enrolled healthy controls, all of whom were Chinese women in Taiwan. Genotyping of polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Ser662Pro, and ERCC5 His1104Asp was performed and used to evaluate breast cancer susceptibility. Of the nonsynonymous polymorphisms, the ERCC5 1104Asp variant was significantly associated with breast cancer (odds ratio = 1.42; 95% confidence interval = 1.08-1.97), and this association was more pronounced in women with lengthy estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (P(trend) = .038). The synergistic effect of multiple genes on the increase of risk was significant in women with a longer period of estrogen exposure (>26 years), greater age at first full-term pregnancy (>26 years), a longer menarche-to-first full-term pregnancy interval (>11 years), and higher body mass index (>22) (all P<.05). This study demonstrates that genotype polymorphisms related to DNA damage repair confer greater susceptibility to endogenous estrogen in the development of breast cancer in women.

Reproductive factors, exogenous female hormone use and breast cancer risk in Japanese: the Miyagi Cohort Study

The incidence of breast cancer among Japanese women is substantially increasing. This population-based prospective cohort study in Japan evaluated the associations of reproductive factors and exogenous female hormone use with breast cancer risk, both overall and separately among premenopausal and postmenopausal women. A total of 24,064 women aged 40-64 were followed from 1990 to 2003. During 309,424 person-years of follow-up, 285 breast cancer cases were documented. In overall evaluation, nulliparity was significantly associated with an increased risk of breast cancer. There was a significant decrease in risk with increasing parity number among parous women (trend P = 0.008). No association was observed between age at menarche or age at first birth and breast cancer risk. Neither oral contraceptive (OC) use nor the use of exogenous female hormones other than OC was associated with breast cancer risk. The evaluation according to menopausal status revealed that nulliparity and parity number were significantly related to breast cancer risk only among postmenopausal women. Later age at natural menopause was associated with an increased risk of breast cancer among postmenopausal women (trend P = 0.02). Our findings suggest that parity number and age at menopause have great effects on breast cancer risk among Japanese women.

FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: Results of a case control study in Japan

Recently, 2 genome-wide association studies demonstrated that single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2 (FGFR2) gene at intron 2 are significantly associated with the risk of female breast cancer. As the next step, it is necessary to evaluate the interaction between these SNPs and known risk factors of breast cancer because such an evaluation could elucidate mechanisms of carcinogenesis and lead to preventive advances. We conducted a case-control study of 456 newly and histologically diagnosed breast cancer cases and 912 age- and menopausal status-matched noncancer controls. The impact of 5 FGFR2 intronic SNPs on the risk of breast cancer and the interactions between these SNPs and various known risk factors of breast cancer were evaluated in both pre and postmenopausal women. We observed a statistically significant association between 4 SNPs and breast cancer risk and these 4 SNPs were in strong linkage disequilibrium in the Japanese population. rs2420946 was associated with a population-attributable risk of 17.7%. We found that FGFR2 polymorphisms interact with family history of breast cancer (interaction p = 0.003) and reproductive risk factors, namely, age at menarche (interaction p = 0.019) and parity (interaction p = 0.026). Of note, a significant association between body mass index (BMI) > or = 25 and FGFR2 polymorphism was observed among postmenopausal women (trend p = 0.012), but not among premenopausal women. In contrast, BMI < 25 had no significant association with this polymorphism regardless of menopausal status. These findings suggest that FGFR2 intronic SNPs affect the reproductive hormone-related pathway and contribute to the development of female breast cancer in the Japanese population.

Interaction of the Effects of Alcohol Drinking and Polymorphisms in Alcohol-Metabolizing Enzymes on the Risk of Female Breast Cancer in Japan

BackgroundEpidemiological studies consistently indicate that alcoholic beverages are an independent risk factor for female breast cancer. Although the mechanism underlying this effect remains unknown, the predominant hypothesis implicates mutagenesis via the ethanol metabolite acetaldehyde, whose impact on the carcinogenesis of several types of cancer has been shown in both experimental models and molecular epidemiological studies. Many of the epidemiological studies have investigated genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His48Arg and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, because of the strong impact these polymorphisms have on exposure to and accumulation of acetaldehyde. With regard to breast cancer, however, evidence is scarce.MethodsTo clarify the impact on female breast cancer risk of the interaction of the effects of alcohol consumption and polymorphisms in the alcohol-metabolizing enzymes ADH1B and ALDH2, we conducted a case–control study of 456 newly and histologically diagnosed breast cancer cases and 912 age- and menopausal status-matched noncancer controls. Gene–gene and gene–environment interactions between individual and combined ADH1B and ALDH2 gene polymorphisms and alcohol consumption were evaluated.ResultsDespite sufficient statistical power, there was no significant impact of ADH1B and ALDH2 on the risk of breast cancer. Neither was there any significant gene–environment interactions between alcohol drinking and polymorphisms in ADH1B and ALDH2.ConclusionsOur findings do not support the hypothesis that acetaldehyde is the main contributor to the carcinogenesis of alcohol-induced breast cancer.

Occupation and cancer – follow-up of 15 million people in five Nordic countries

Occupation and cancer – follow-up of 15 million people in five Nordic countries

The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report

trance) of breast and ovarian cancers among female family members with BRCA1 and BRCA2 mutation. Methods: Among the 61 BRCA1 mutation carriers in the 42 families and 47 BRCA2 mutation carriers in 31 families identified at 5 academic breast clinics, the probands were excluded to estimate the cumulative risk till each age of breast cancer in the Korean BRCA1 and BRCA2 carriers. Using Kaplan-Meier analyses, cumulative cancer risk estimates were determined. Results: By the age 70, the female breast cancer risk for the BRCA1 and BRCA2 mutation carriers was 72.1% (95% confidence interval [CI]=59.5% to 84.8%) and 66.3% (95% CI=41.2% to 91.5%), respectively, and the ovarian cancer risk was 24.6% (95% CI=0% to 50.3%) and 11.1% (95% CI= The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report