Breast Hypertrophy
Introduction
Breast hypertrophy refers to the condition characterized by abnormally large breast tissue. Breast size is a complex, polygenic trait, meaning it is influenced by interactions among multiple genes. Understanding the genetic factors that contribute to variations in breast size is crucial not only for comprehending normal human development but also for identifying potential links to various health conditions and diseases.
Biological Basis
Genetic studies have identified several genomic regions and single nucleotide polymorphisms (SNPs) associated with variations in breast size. For instance, specific variants such as rs7816345 near the ZNF703 gene, rs4849887 near INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG have been significantly associated with breast size. [1] Many of these genes and regions play roles in breast development, estrogen regulation, and have established connections to breast cancer. [1] For example, the ESR1 gene encodes Estrogen Receptor 1, which is vital for estrogen signaling and breast tissue growth. [1] The ZNF703 region is known to be amplified in breast tumors, and AREG mediates estrogen function during breast development. [1] These findings suggest that the biological pathways underlying normal breast development may share common genetic factors with certain disease risks.
Clinical Relevance
The study of breast hypertrophy holds clinical relevance due to its potential associations with other health indicators. In research, breast size is often assessed through self-reported bra cup and band sizes. [1] A significant area of clinical interest is the relationship between breast size, mammographic density, and breast cancer risk. Mammographic density, which is the percentage of non-fat breast tissue observed in a mammogram, is a known independent risk factor for breast cancer. [1] While the precise epidemiological links between breast size and breast cancer are still being investigated, genetic variants that influence breast size can provide insights into the fundamental biological processes contributing to both typical breast morphology and breast cancer susceptibility. [1] Such genetic insights could potentially contribute to the development of new screening methods or preventative strategies.
Social Importance
Beyond its biological and clinical aspects, breast hypertrophy can carry substantial social and personal implications. Individuals with significantly large breasts may experience physical discomfort, including chronic back pain, neck pain, and shoulder grooving, as well as challenges with physical activity and finding appropriate clothing. The condition can also impact body image, self-esteem, and overall quality of life, leading some individuals to consider medical interventions like breast reduction surgery. Research into the genetic underpinnings of breast size contributes to a broader understanding of human variation and provides foundational knowledge that can inform medical guidance and support for affected individuals.
Methodological and Statistical Considerations
Genome-wide association studies (GWAS) on breast phenotypes often face inherent methodological and statistical limitations. Initial discovery stages frequently operate with relatively small sample sizes, which can limit the statistical power to reliably detect genetic variants with subtle effects or to achieve genome-wide significance, potentially leading to an underestimation of the genetic architecture of breast hypertrophy . [2], [3] While subsequent meta-analyses and replication cohorts significantly boost overall sample size and enhance the consistency of findings, the initial discovery phase can be susceptible to effect-size inflation, commonly known as "winner's curse," where the observed effect in the discovery set is larger than the true effect . [4], [5]
Further challenges arise from the variability in genotyping platforms and data processing algorithms utilized across different studies, which can complicate the direct comparison and integration of results . [5], [6] Moreover, the widespread practice of using imputed genotype data, despite generally high imputation quality, may influence the precise estimation of association strengths for specific variants, underscoring the importance of direct genotyping for robust replication . [1], [5] Although genomic inflation factors are typically low, suggesting minimal impact from population substructure, genuine heterogeneity in genetic effects can still exist across diverse cohorts or study designs, manifesting as limited overlap in significant associations or varying effect magnitudes, which necessitates sophisticated meta-analytical approaches to accurately quantify and address such variability . [1], [5], [6], [7]
Phenotypic Definition and Population Generalizability
The precise definition and measurement of breast phenotypes, crucial for understanding breast hypertrophy, present significant limitations. For instance, relying on self-reported bra size as a proxy for breast volume, while practical for large-scale studies, is recognized as an imprecise measure that can introduce considerable noise into genetic association analyses, potentially obscuring the true genetic underpinnings of breast hypertrophy. [1] Similarly, while some studies standardize mammographic density measurements by using a single reader, variations in mammography views and imaging software across different participant cohorts can still impact the consistency and comparability of the density phenotype. [5]
A notable limitation across several studies is the predominant focus on populations of European ancestry . [2], [5] While this demographic focus helps to minimize confounding from population stratification within the studied groups, it substantially restricts the generalizability of identified genetic associations to other, more diverse populations. Different ancestral groups may possess distinct genetic architectures, allele frequencies, or linkage disequilibrium patterns, implying that genetic variants discovered in one population might not be relevant or exert the same effect in others, thereby highlighting the urgent need for more ethnically inclusive research to fully understand the genetic basis of breast hypertrophy across humanity . [2], [6]
Unaccounted Factors and Causal Mechanisms
While studies typically adjust for known confounding variables such as age, body mass index (BMI), menopausal status, and prior breast surgeries (e.g., augmentation or reduction), the intricate interplay of environmental factors and gene-environment interactions remains largely uncharacterized in the context of breast hypertrophy . [1], [5] Unmeasured lifestyle factors, varying hormonal exposures, or other environmental influences not accounted for in study designs could substantially modulate genetic effects on breast phenotype, contributing to a portion of the unexplained phenotypic variation. Future research must delve deeper into these complex interactions to develop a comprehensive understanding of breast hypertrophy's etiology.
Current GWAS primarily identify genetic variants associated with a trait, often serving as statistical markers that are in linkage disequilibrium with, rather than being, the direct causal mutations . [2], [3] Significant gaps persist in fine-mapping these associated genomic regions to pinpoint the exact causal variants and to elucidate the precise biological pathways and mechanisms through which they influence breast development and size . [1], [2] The concept of "missing heritability" suggests that a substantial proportion of the genetic contribution to breast hypertrophy, potentially involving rare variants, structural variations, or complex epistatic interactions, has yet to be discovered, necessitating the application of advanced sequencing technologies and functional genomic studies for a more complete elucidation of its genetic architecture. [2]
Variants
Genetic variations play a significant role in determining breast size and susceptibility to conditions like breast hypertrophy, a trait influenced by complex interactions between multiple genes and environmental factors. Several single nucleotide polymorphisms (SNPs) and their associated genes have been implicated in the development and regulation of breast tissue.
Variants within or near genes involved in hormonal signaling and mammary gland development are particularly relevant. PTHLH (Parathyroid Hormone-Like Hormone) encodes a member of the parathyroid hormone family, which is crucial for embryonic mammary gland development and lactation. [1] Alterations such as rs11049272 and rs7297051 in the PTHLH-CCDC91 region may influence these developmental processes, potentially leading to variations in breast size. Similarly, ESR1 (Estrogen Receptor 1) encodes the alpha estrogen receptor, a protein vital for binding estrogen and regulating gene expression that drives normal breast development and can impact breast cancer risk. [1] The variant rs6904031 near ESR1 could modify receptor activity or expression, thereby affecting the sensitivity of breast tissue to estrogen and contributing to excessive cell proliferation and breast hypertrophy.
Other critical genes influencing breast size include those involved in estrogen synthesis and regulation. CYP19A1 encodes aromatase, the enzyme responsible for converting androgens into estrogens, a key step in estrogen biosynthesis. Elevated estrogen levels are a known driver of breast tissue proliferation, making variants like rs7173595 in CYP19A1 potentially impactful by modulating local or systemic estrogen concentrations. Such genetic changes could lead to increased estrogen exposure, fostering excessive growth of glandular and stromal components and contributing to breast hypertrophy. [7] While less understood in this context, MIR4713HG acts as a host gene for microRNAs that can regulate gene expression. Variants in this region, also including rs7173595, might indirectly affect cellular pathways involved in breast tissue growth or hormonal responses.
Beyond direct hormonal pathways, variants in genes governing fundamental cellular processes can also contribute to breast size variation. RAB3GAP2 functions as a GTPase-activating protein for Rab proteins, which are essential regulators of membrane trafficking and cell signaling. A variant like rs557235116 could subtly alter these cellular functions, thereby influencing the growth and structural organization of breast tissue. [1] Furthermore, the region near KCNU1 and SMARCE1P4, containing rs10092900, is of interest. KCNU1 encodes a potassium channel that regulates cell volume and proliferation, while SMARCE1P4 is a pseudogene whose vicinity might harbor regulatory elements affecting nearby functional genes. Similarly, variants like rs146151364 within the LINC02463-MED13L region could impact transcriptional regulation, as LINC02463 is a long non-coding RNA and MED13L is part of a key transcriptional complex. [7] Such genetic variations can lead to an imbalance in growth signals, potentially contributing to the development of breast hypertrophy.
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs11049272 rs7297051 |
PTHLH - CCDC91 | breast hypertrophy |
| rs7173595 | CYP19A1, MIR4713HG | waist-hip ratio BMI-adjusted waist-hip ratio estradiol measurement osteoporosis breast hypertrophy |
| rs557235116 | RAB3GAP2 | breast hypertrophy Abnormality of the breast |
| rs10092900 | KCNU1 - SMARCE1P4 | type 2 diabetes mellitus breast carcinoma diabetes mellitus glucose measurement breast hypertrophy |
| rs6904031 | ESR1 | breast carcinoma cancer uterine fibroid breast hypertrophy Abnormality of the breast |
| rs146151364 | LINC02463 - MED13L | breast hypertrophy |
Classification, Definition, and Terminology
Breast hypertrophy, understood as variations in natural breast size, is a complex trait influenced by a combination of genetic, hormonal, and environmental factors. Its definition and classification in research contexts often rely on operational measurements and an understanding of its intricate relationships with other physiological characteristics and disease risks.
Defining Breast Size and its Assessment
Breast size, as a phenotypic trait, is often operationally defined and measured through self-reported bra dimensions in large-scale genetic studies. Participants typically provide their bra cup size from a range of categories, such as "Smaller than AAA" up to "Larger than DDD," and their bra band size in inches. [1] This participant-driven data collection method allows for a practical assessment of variations in breast morphology across large populations. [1] While bra size offers an accessible metric, it is acknowledged within scientific discourse that it is not a perfect proxy for actual breast volume. [1]
To enhance the accuracy and clinical relevance of self-reported bra size, research studies frequently incorporate bra band size as a crucial covariate. [1] Controlling for bra band size has been shown to improve the correlation between cup size and actual breast volume, providing a more refined measure of breast dimensions. [8] Furthermore, bra band size is recognized for its correlation with Body Mass Index (BMI), often serving as a proxy for BMI in breast size research, especially when comprehensive BMI data is less consistently available. [1] This approach highlights the interplay between general body adiposity and localized breast tissue volume in the operational definition and measurement of breast size.
Related Physiological and Clinical Concepts
The understanding of breast size is intrinsically linked to several other physiological and clinical concepts that bear significance for overall breast health, particularly in relation to breast cancer risk. Mammographic density, defined as the percentage of non-fat breast tissue observed in a mammogram, is a well-established independent risk factor for breast cancer. [9] Although distinct from overall breast size, both traits reflect aspects of breast tissue composition and development, and genetic studies have begun to explore shared underlying biological pathways between them. [10]
Body weight and Body Mass Index (BMI) also exhibit a complex relationship with breast size and breast cancer risk. Higher body weight is generally positively correlated with breast size. [1] The association with breast cancer risk varies with age and timing of weight changes: higher weight at younger ages may decrease premenopausal and postmenopausal breast cancer risk, while adult weight gain tends to increase postmenopausal breast cancer risk. [11] Additionally, breast asymmetry, which refers to a noticeable difference in size or shape between the two breasts, has been investigated for its potential association with breast cancer risk. [12] These interconnected factors underscore the multifactorial nature of breast morphology and its broader clinical implications.
Genetic Influences on Breast Size and Associated Pathways
Recent genomic research has elucidated a genetic basis for natural variation in breast size, identifying specific genetic variants significantly associated with this trait. [1] These studies utilize genome-wide association study (GWAS) approaches to pinpoint single nucleotide polymorphisms (SNPs) linked to breast size, employing stringent statistical thresholds for genome-wide significance. [1] The identification of such genetic loci provides a conceptual framework for understanding the underlying biological mechanisms that regulate breast development and morphology, offering insights beyond purely environmental or lifestyle factors. [1]
Several key genomic regions and genes have been implicated in breast size determination, often with connections to breast cancer and estrogen pathways. For instance, specific SNPs such as rs7816345 have been identified in the 8p12 region, which is amplified in breast tumors and contains the breast cancer oncogene ZNF703. [1] Other associations include rs4849887 near INHBB, a gene linked to estrogen regulation and obesity, and rs12173570 near ESR1 (estrogen receptor 1). [1] Further genetic variants, like rs7089814 in ZNF365 and rs12371778 near PTHLH, along with a locus near AREG (which plays a role in mediating estrogen function in breast development), underscore the complex genetic architecture underlying breast size and its relevance to breast cancer pathogenesis. [1] These findings highlight a shared genetic architecture between breast size and breast cancer risk, suggesting that understanding the biology of breast development may offer insights into breast cancer pathogenesis. [1]
Causes of Breast Hypertrophy
Breast hypertrophy, characterized by an abnormally large breast size, is influenced by a complex interplay of genetic predispositions, hormonal regulation, and developmental factors. Research indicates that this trait is not solely determined by a single factor but rather arises from multiple contributing elements.
Genetic Predisposition and Hormonal Regulation
Genetic factors play a significant role in determining breast size, with multiple inherited variants contributing to an individual's predisposition for breast hypertrophy. Genome-wide association studies (GWAS) have identified specific regions containing single nucleotide polymorphisms (SNPs) significantly associated with breast size. For instance, variants such as rs7816345 near ZNF703, rs4849887 and rs17625845 flanking INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG have been linked to variations in breast size. [1] These genes are intricately involved in key biological processes, including breast development and estrogen regulation, highlighting the polygenic nature of breast size determination.
The mechanisms through which these genetic variants contribute to breast hypertrophy often involve hormonal pathways. For example, ESR1 encodes for estrogen receptor 1, a critical component in mediating estrogen's effects on breast tissue growth. Similarly, AREG (amphiregulin) is known to mediate estrogen function in breast development, and INHBB (inhibin, beta B) has connections to estrogen regulation, as well as obesity and uterine cancer. . This hormonal influence is further modulated by growth factors like PTHLH (parathyroid hormone-like hormone), which is crucial for normal mammary gland function and interacts with its receptor, PTH1R, to stimulate processes such as ductal outgrowth during embryonic development, often in concert with factors like BMP4 and PTHrP. [13] Differential signal transduction through alternatively spliced FGFR2 variants expressed in human mammary epithelial cells also highlights the specificity and complexity of receptor activation in influencing cellular responses and ultimately breast tissue architecture. [14] The broader ErbB signaling network, involving receptors like ERBB4, further underscores the multifaceted nature of growth factor control over breast cell proliferation and differentiation. [7]
Cell Growth, Differentiation, and Morphogenesis
Cellular proliferation, differentiation, and overall mammary morphogenesis are tightly regulated by several interconnected intracellular signaling cascades and transcription factor networks. The Wnt/β-catenin pathway plays a pivotal role in cell fate determination, stem cell regulation, and cell differentiation and proliferation, with its activity negatively regulated by proteins like KREMEN1, whose expression is often reduced in human tumors. [13] Similarly, the TGF-β pathway is a major determinant in breast development and progression, often interacting with MAP kinase pathways, such as those involving JNK and NF-κB, which are critical for controlling cell growth and death. [15] Specific components like TAB2, an activator of MAP3K7/TAK1, are essential for IL-1-induced activation of these MAP kinases, illustrating intricate intracellular signaling cascades that orchestrate cellular responses. [15] Transcription factors like PAX9 and FOXQ1 further regulate cell proliferation, migration, and resistance to apoptosis, with FOXQ1 also being implicated in mesenchymal-epithelial transition and breast cancer metastasis. [13]
Metabolic Regulation and Adipose Tissue Influence
Metabolic pathways play a significant role in influencing breast tissue volume and composition, particularly through the regulation of energy metabolism and adipose tissue. Genetic variants near genes like FTO and INHBB have been linked to obesity and metabolic diseases, suggesting a connection between systemic metabolic status and local breast tissue characteristics. [13] The expression of Inhibin beta B, for instance, is notably high in human adipocytes and is responsive to weight loss, directly correlating with factors implicated in metabolic disease and highlighting its role in adipose tissue regulation within the breast. [16] Furthermore, circulating levels of metabolic hormones such as insulin and C-peptide are associated with breast cancer risk, indicating that broader metabolic regulation and flux control can significantly impact breast health and potentially contribute to conditions of breast hypertrophy. [17] These metabolic influences represent a critical layer of control over tissue growth and maintenance, with dysregulation potentially leading to excessive tissue accumulation.
Genomic Regulation and Oncogenic Drivers
The regulation of breast tissue growth and potential hypertrophy is also profoundly influenced by genomic stability, gene regulation, and the activity of specific oncogenes and tumor suppressors. Amplification of genes like ZNF703 in the 8p12 region, for example, is a characteristic of luminal B breast cancer and plays a role in differentially regulating luminal and basal progenitors in human mammary epithelium, thereby impacting overall tissue development and aberrant growth. [18] Other genes, including ZNF45, ZNF222, and ZNF283, are also thought to be involved in transcriptional regulation, exerting control over gene expression programs critical for cell fate and proliferation. [13] DNA repair pathways, involving genes such as MUS81 and SSBP4, are essential for maintaining genomic integrity, with SSBP4 specifically suggested to have tumor suppressor activity that, when compromised, could contribute to dysregulated cell growth. [13] Moreover, oncogenes like ARHGEF5 and MKL1 are crucial for tumor cell invasion and metastasis in breast cancer, while the cofilin gene (CFL1) is vital for tumor cell motility, illustrating how dysregulation of these mechanisms can drive pathological tissue expansion and progression. [13]
Genetic Basis and Risk Assessment
Studies have revealed that genetic variants influencing normal breast development and size also play a role in breast cancer risk. For instance, specific single nucleotide polymorphisms (SNPs) near genes like ESR1, PTHLH, ZNF365, ZNF703, INHBB, and AREG have been linked to breast size, and some of these are also associated with breast cancer. [1] Understanding these shared genetic factors provides insight into the underlying biology of breast morphology and its predisposition to disease, potentially aiding in the development of novel screening tools for individuals at higher risk.
Association with Breast Cancer Risk and Prognosis
While the direct epidemiological relationship between breast size and cancer is complex, research indicates that larger breast size can be associated with an increased risk of breast cancer, particularly in lean women. [1] For example, studies have shown that among women with a body mass index (BMI) under 25, those with a cup size of D or larger had a 1.8 times higher risk of breast cancer than those with a cup size of A or smaller. [1] This association highlights breast morphology as a potential indicator in risk stratification, alongside other established risk factors like mammographic density and body weight, which also exhibit intricate relationships with breast cancer risk. Further research into these interactions could refine prognostic models and inform long-term patient care strategies.
Clinical Applications and Personalized Strategies
The identification of genetic variants influencing both breast size and cancer risk, along with the observed epidemiological link between larger breast size and increased cancer risk in certain populations, offers avenues for personalized medicine. Clinicians could potentially use genetic information related to breast development and size, combined with morphological assessments, to identify individuals at higher risk for breast cancer. This stratified risk assessment could then guide tailored monitoring strategies, such as more frequent or advanced imaging, and inform discussions about preventive measures, ultimately enhancing patient care by moving towards more individualized risk management.
Frequently Asked Questions About Breast Hypertrophy
These questions address the most important and specific aspects of breast hypertrophy based on current genetic research.
1. My mom and sister have large breasts; will I definitely have them too?
Not necessarily, but your family history suggests a higher genetic predisposition. Breast size is influenced by many genes, not just one, so while you share some genetic factors with your family, the exact combination and how they interact can be unique to you. Lifestyle and other factors also play a role in how these genetic influences manifest.
2. Does my diet make my breasts grow bigger?
While genetics are a primary driver of breast size, your diet can play a role, especially if it impacts your overall body mass index (BMI). Maintaining a healthy weight through diet can help manage overall body fat, which can contribute to breast size. Hormonal exposures influenced by lifestyle factors might also subtly modulate genetic effects.
3. Why do some people have much larger breasts than others?
Breast size is a complex trait influenced by many genes interacting together. Genetic studies have pinpointed specific regions in our DNA that contribute to variations in breast size, affecting things like breast development and estrogen regulation. This genetic diversity is why there's such a wide range of breast sizes among individuals.
4. Can exercise help prevent my breasts from getting larger?
Exercise primarily influences your overall body composition and muscle mass, not the underlying genetic predisposition for breast tissue growth. While regular physical activity can help maintain a healthy BMI, which may impact the fatty tissue in breasts, it won't fundamentally change the genetically determined glandular tissue size. However, it can help alleviate physical discomforts.
5. Having large breasts, am I at higher cancer risk?
The relationship between breast size and breast cancer risk is complex and still being investigated. However, genetic variants that influence breast size often affect genes involved in breast development and estrogen regulation, which also have established connections to breast cancer. Doctors also look at mammographic density, which is linked to cancer risk and can be influenced by these genetic factors.
6. Is the back pain from my large breasts genetic?
The back pain itself isn't genetic, but your predisposition to having larger breasts, which can cause the pain, is significantly influenced by your genes. Your genetic makeup determines many aspects of breast development, and for some, this leads to hypertrophy that can cause physical discomforts like chronic back and neck pain.
7. Does my family's ethnic background make my breasts larger?
Research on breast size has largely focused on populations of European ancestry, meaning we don't fully understand the genetic influences in other ethnic groups. It's possible that different ancestral backgrounds have distinct genetic architectures or allele frequencies that could influence breast size differently. More inclusive research is needed to fully understand these variations.
8. Does my breast size change a lot as I age?
Yes, breast size can change with age, primarily due to hormonal shifts. Factors like menopausal status are known to influence breast morphology. While your underlying genetic predisposition for breast size remains constant, hormonal changes throughout your life can modulate how your breasts appear and feel.
9. Can I overcome my genes to have smaller breasts?
While genetics strongly predispose you to a certain breast size, lifestyle factors like maintaining a healthy BMI can influence the fatty component of your breasts. For significant reduction, medical interventions like breast reduction surgery are often considered, as they address the physical tissue directly, which is primarily determined by your genes.
10. Could a genetic test explain my large breast size?
Current genetic studies have identified specific gene regions and variants associated with breast size, such as those near genes involved in estrogen regulation and breast development. While these findings contribute to understanding the genetic basis, a single genetic test isn't typically used to "explain" individual breast size, as it's a complex trait with many contributing factors. However, genetic insights help understand your predisposition.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
[1] Eriksson N, et al. Genetic variants associated with breast size also influence breast cancer risk. BMC Med Genet. 2012;13:53.
[2] Rinella, E. S., et al. "Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation." Hum Genet, vol. 132, no. 5, 2013, pp. 517-27.
[3] Sehrawat, B., et al. "Potential novel candidate polymorphisms identified in genome-wide association study for breast cancer susceptibility." Hum Genet, vol. 130, no. 2, 2011, pp. 241-52.
[4] Ahmed, S., et al. "Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2." Nat Genet, vol. 41, no. 5, 2009, pp. 585-90.
[5] Stevens, K. N., et al. "Identification of a novel percent mammographic density locus at 12q24." Hum Mol Genet, vol. 21, no. 13, 2012, pp. 3086-93.
[6] Gold, B., et al. "Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33." Proc Natl Acad Sci U S A, vol. 105, no. 10, 2008, pp. 4002-7.
[7] Kim HC, et al. A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study. Breast Cancer Res. 2012;14(2):R50.
[8] Ringberg, A, et al. "Of cup and bra size: reply to a prospective study of breast size and premenopausal breast cancer incidence." International Journal of Cancer, vol. 119, no. 9, 1 Nov. 2006, pp. 2242–2243.
[9] Boyd, NF, et al. "Mammographic Density and the Risk and Detection of Breast Cancer." New England Journal of Medicine, vol. 356, no. 3, 18 Jan. 2007, pp. 227–236.
[10] Lindstrom, S, et al. "Common variants in ZNF365 are associated with both mammographic density and breast cancer risk." Nature Genetics, vol. 43, no. 2, 23 Jan. 2011, pp. 185–187.
[11] Baer, HJ, et al. "Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study." Breast Cancer Research, vol. 7, no. 4, 15 June 2005, pp. R314–R325.
[12] Scutt, D, et al. "Breast asymmetry and predisposition to breast cancer." Breast Cancer Research, vol. 8, no. 2, 20 Mar. 2006, p. R14.
[13] Michailidou, K., et al. "Large-scale genotyping identifies 41 new loci associated with breast cancer risk." Nat Genet, 2013, PMID: 23535729.
[14] Hunter, D. J., et al. "A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer." Nat Genet, vol. 39, 2007, pp. 870–874.
[15] Long, J., et al. "Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer." PLoS Genet, 2012, PMID: 22383897.
[16] Sjoholm, K., et al. "The expression of inhibin beta B is high in human adipocytes, reduced by weight loss, and correlates to factors implicated in metabolic disease." Int J Obes (Lond), vol. 34, 2010, pp. 1530–1538.
[17] Eliassen, A. H., et al. "Circulating insulin and c-peptide levels and risk of breast cancer among predominately premenopausal women." Cancer Epidemiol Biomarkers Prev, vol. 16, 2007, pp. 161–164.
[18] Sircoulomb, F., et al. "ZNF703 gene amplification at 8p12 specifies luminal B breast cancer." EMBO Mol Med, vol. 3, 2011, pp. 153–166.