Preface

Abstract

Over the past several decades, the global incidence rate of breast cancer has increased continuously [1][2][3][4] with the most rapid increase occurring in economically developing countries [4]. In 2008, approximately 1.3 million new cases of breast cancer were diagnosed, accounting for 23 % of all cancers [3] and making breast cancer the most commonly diagnosed cancer in women [3,5]. Approximately, 55 % of breast cancer cases were diagnosed in developed countries and the remaining 45 % of the cases were diagnosed in developing countries [3]. Although breast cancer is the most common cancer in women worldwide, developed countries have a higher overall incidence rate and a three-fold higher age-standardized rate [4]. In Western Europe, the incidence rate is 89.7 per 100,000 women while in Eastern Africa, the incidence rate is 19.3 per 100,000 women [3]. Although the global incidence rate of breast cancer is increasing, the underlying causes of the disease are still largely unknown. During the 1980s, screening practices, access to mammography, and the use of exogenous estrogens and progestins contributed to the high incidence rates in developed countries, but these factors do not explain the increase in these countries before the 1980s or the increase in countries with low rates of screening and use of hormones [6]. It has been suggested that the increasing incidence is due to a combination of an increase in the prevalence of known risk factors and to new unidentified risk factors [2,7]. Family history is a risk factor for developing breast cancer (8), but only 5-10 % of breast cancers are associated with the highly penetrant BRCA1 and BRCA2 genes [8]. In contrast to family history, endocrine status is a prominent risk factor for developing breast cancer. Early age at menarche [9,10], late age at menopause [11,12], and later age at first full-term pregnancy [13] increase the risk of developing the disease. Exposure to exogenous estrogens and progestins after menopause [14][15][16] and a history of benign breast disease also increase the risk of developing breast cancer. These well established risk factors, i.e., family history, reproductive and menstrual history, and history of benign breast disease, are estimated to account for only about 40 % of breast cancer cases [17]. Childhood exposure to ionizing radiation [18][19][20], adult alcohol consumption [21], and obesity [7,22,23] also increase the risk of developing breast cancer. However, these risk factors are unlikely to account for the remaining cases of the disease [2,7,24] suggesting that there are still unidentified causes of breast cancer.There are many challenges to identifying risk factors for developing breast cancer including, but not limited to, the type of exposure, e.g., environmental estrogens, carcinogens, and mutagens; the influence of genetics on the response to the exposure, a.k.a., gene-environment interactions; and the timing of the exposure. The breast is unique and complex in that it grows and develops throughout the lifetime of a female [2...

High-resolution association mapping of number of teats in pigs reveals regions controlling vertebral development

“…precursor structures for vertebrae, in the induction of mammary gland development [22, 25, 27]. Although to our knowledge, a variation in number of somites (vertebrae) in mice has not been subject to study in mice, and certainly not in relationship to the number of mammary glands or nipples/teats, it is clear that altered somitic development or gene expression can alter the number of mammary glands (thus nipples/teats) in mice [22, 25, 27]. In agreement with this biological mechanism of mammary gland development, we identified in our current study several candidate genes with a known association to vertebrae development.…”

“…Whereas wild type mice normally form five pairs of mammary glands along the mammary lines [22], modification of certain genes can alter this number [25]. For example, loss of either Nrg3 , Pax3 , Gli3 , Fgf10 , or Hoxc6 [26–29] abolishes the formation of different, gene-specific, subsets of MRs [25]. Deletion of e.g.…”

“…Conversely, ectodermal overexpression of the genes encoding the receptor ligands Eda-A1 (Ectodysplasin-A1) [36] or Nrg3 [37], or suppression of the Wnt-antagonists Lrp4 or Wise/Sostdc1, may lead to formation of one or several supernumerary mammary glands in a gene-specific pattern or region along the mammary line [38, 39]. These data provide evidence for genetic determinants for the number of mammary glands, and moreover, for the positional variation in activity of, or requirement for, these genetic determinants along the mammary line [25]. …”