FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 1029-1031 ◽  
Author(s):  
Yussanne P. Ma ◽  
Flora E. van Leeuwen ◽  
Rosie Cooke ◽  
Annegien Broeks ◽  
Victor Enciso-Mora ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hodgkin Lymphoma ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Control Series ◽  
Cancer Risk Factors ◽  
Increased Risk

Abstract Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.

scholarly journals Mendelian randomisation study of smoking exposure in relation to breast cancer risk

2021 ◽  
Author(s):  
Hanla A. Park ◽  
Sonja Neumeyer ◽  
Kyriaki Michailidou ◽  
Manjeet K. Bolla ◽  
Qin Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Causal Effect ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Smoking Exposure

Abstract Background Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07–1.30, P = 0.11 × 10–2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78–1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

scholarly journals Do Alterations in Mitochondrial DNA Play a Role in Breast Carcinogenesis?

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Thomas E. Rohan ◽  
Lee-Jun Wong ◽  
Tao Wang ◽  
Jonathan Haines ◽  
Geoffrey C. Kabat
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mitochondrial Dysfunction ◽  
Genetic Variants ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Breast Carcinogenesis ◽  
Mtdna Mutations ◽  
Increased Risk

A considerable body of evidence supports a role for oxidative stress in breast carcinogenesis. Due to their role in producing energy via oxidative phosphorylation, the mitochondria are a major source of production of reactive oxygen species, which may damage DNA. The mitochondrial genome may be particularly susceptible to oxidative damage leading to mitochondrial dysfunction. Genetic variants in mtDNA and nuclear DNA may also contribute to mitochondrial dysfunction. In this review, we address the role of alterations in mtDNA in the etiology of breast cancer. Several studies have shown a relatively high frequency of mtDNA mutations in breast tumor tissue in comparison with mutations in normal breast tissue. To date, several studies have examined the association of genetic variants in mtDNA and breast cancer risk. The G10398A mtDNA polymorphism has received the most attention and has been shown to be associated with increased risk in some studies. Other variants have generally been examined in only one or two studies. Genome-wide association studies may help identify new mtDNA variants which modify breast cancer risk. In addition to assessing the main effects of specific variants, gene-gene and gene-environment interactions are likely to explain a greater proportion of the variability in breast cancer risk.

Association of APC and MCC Polymorphisms with Increased Breast Cancer Risk in an Indian Population

2011 ◽  
Vol 26 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Nupur Mukherjee ◽  
Nilanjana Bhattacharya ◽  
Satyabrata Sinha ◽  
Neyaz Alam ◽  
Runu Chakravarti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Risk Of Cancer

The adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC) genes are key regulatory genes of the Wnt/β-catenin signaling pathway, which are independently involved in maintaining low levels of β-catenin in the cell. In addition to genetic and epigenetic alterations, some genetic polymorphisms in the genes associated with the Wnt signaling pathway have been reported to be associated with an increased risk of cancer, including breast cancer. In the present study we analyzed the association of genotype and haplotype status of two single nucleotide polymorphisms (SNPs), rs2229992 and rs11283943, in the APC and MCC genes, respectively, with an increased risk of breast carcinogenesis in a breast cancer and control population from eastern India. We observed a significant association of the rs11283943 SNP with increased breast cancer risk. Two specific haplotypes involving the minor allele of rs11283943 were found to be associated with an increased breast cancer risk. Kaplan-Meier curves showed a significant association of the 2–2 genotype (genotype homozygous for the rs11283943 minor allele) with decreased survival (p=0.045) of the breast cancer patients in our study, in particular patients with early-onset BC.

scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Estrogen Receptor Α ◽  
Epidemiological Studies ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Increased Risk ◽  
The Impact

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

scholarly journals Chromatin interactome mapping at 139 independent breast cancer risk signals

2019 ◽  
Author(s):  
Jonathan Beesley ◽  
Haran Sivakumaran ◽  
Mahdi Moradi Marjaneh ◽  
Luize G. Lima ◽  
Kristine M. Hillman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Target Genes ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Breast Cancer Cell Lines ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Candidate Target

ABSTRACTGenome-wide association studies have identified 196 high confidence independent signals associated with breast cancer susceptibility. Variants within these signals frequently fall in distal regulatory DNA elements that control gene expression. We designed a Capture Hi-C array to enrich for chromatin interactions between the credible causal variants and target genes in six human mammary epithelial and breast cancer cell lines. We show that interacting regions are enriched for open chromatin, histone marks for active enhancers and transcription factors relevant to breast biology. We exploit this comprehensive resource to identify candidate target genes at 139 independent breast cancer risk signals, and explore the functional mechanism underlying altered risk at the 12q24 risk region. Our results demonstrate the power of combining genetics, computational genomics and molecular studies to rationalize the identification of key variants and candidate target genes at breast cancer GWAS signals.

Identifying women at increased risk of breast cancer: Can we use genotyping at low penetrance loci?

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 162-162
Author(s):  
C. Merrick ◽  
J. Dunlop ◽  
L. Baker ◽  
E. Gellatly ◽  
A. Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Control Group ◽  
Risk Category ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Combining Data

162 Background: Most inherited predisposition to breast cancer is attributable to low penetrance susceptibility loci, a number of which have been identified through genome-wide association studies. Although individually each locus has a small effect, combining data from multiple loci would be expected to provide more risk information. We investigated the size of risk determination that can be achieved using genotyping at 18 loci. We then calculated its effect when combined with risk estimated from family history alone in terms of management under UK guidelines, where a woman who has a 10 year risk of 3% or greater requires additional breast screening from a younger age. Methods: Genotyping for 18 loci was carried out in 253 women at increased risk of breast cancer due to a positive family history and 118 matched controls. The relative risks conferred by genotype at the 18 loci were combined under a log-additive model and transformed into a log-polygenic risk. The BOADICEA risk estimation tool was used to calculate breast cancer risk due to family history. Results: Both the increased risk and control groups demonstrated a normal distribution of log-polygenic risk with similar variance. There was a significantly higher mean in the increased risk compared to the control group (mean = 0.1313 and 0.0874 respectively, p = 0.007). No significant correlation was found between polygenic risk calculated from genotype data and the family history risk estimated using BOADICEA. When polygenic risk was combined with family history risk there was significant reclassification of risk for those with a family history. 36.76% moved into a higher risk category while 3.68% moved into a lower risk category. Conclusions: Our data suggests that genotyping will be clinically relevant for estimating breast cancer risk. Individuals with a family history overall have a higher genotype risk than the population. The lack of correlation of genotype risk with BOADICEA risk suggests that the two risk estimates can be considered independently. By combining genotype with family history data, we demonstrated a significant reclassification of risk for individuals with a family history, with better identification of women in this group requiring intervention.

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