Abstract
Researchers have demonstrated that a very low dose of aspirin could result in a long-term reduction in colorectal cancer.
Recently, there has been evidence suggesting that using aspirin on a daily basis decreases the risk of cancer; however, the evidence for alternate-day use is scarce. Subsequently, a recent study conducted by Nancy Cook (Brigham and Women's Hospital, Boston, MA, USA) and colleagues set out to analyze the relationship between long-term, alternate-day aspirin and cancer in healthy women. The findings of which were published in Annals of Internal Medicine.
When talking to Women's Health, Cook explained that the Women's Health Study (ClinicalTrials.gov: NCT00000479) “is the only trial designed to specifically consider the long-term effect of aspirin on cancer incidence.” In addition, “this trial is also the first to look at this question in large numbers of women. Previous studies included in meta-analyses were either conducted solely in men or included mostly men because they were among those who already had heart disease.”
The study involved 39,876 women who were at least 45 years of age. A total of 33,682 of these women continued observational follow-up. The study involved the administration of “100 mg of alternate-day aspirin or placebo through March 2004, with a median 10-year follow-up.” Furthermore, the post-trial follow-up continued through March 2012 with the measurement being cancer incidence.
In the study, the authors confirmed a total of 5071 cases of cancer and 1391 cancer deaths. They also stated, “Over the entire follow-up, aspirin had no association with total, breast or lung cancer.” In addition, it was observed that there was a reduction in colorectal cancer in the aspirin group, especially for proximal colon cancer. The observed difference became apparent after 10 years, with a post-trial reduction of 42%. The authors mentioned, “There was no extended effect on cancer deaths of colorectal polyps.” Furthermore, there were increased occurrences of gastrointestinal bleeding and peptic ulcers in the aspirin group.
“…this is the first evidence that a very low dose of aspirin … can lead to a long-term reduction in colorectal cancer.”
This study was not without its challenges. Initially, the trial included 39,876 women who were involved in the intervention for 10 years, on average. The investigators then had to follow the women for an additional 8 years to observe the effect on colorectal cancer. The group explained, “It was a challenge to keep follow-up rates high and to collect high quality data in an era of reduced NIH funding for medical research.”
Cook told Women's Health, “The work is important because this is the first evidence that a very low dose of aspirin, 100 mg taken every other day, can lead to a long-term reduction in colorectal cancer.” The specific dose is an important factor as higher doses could result in more adverse effects. The authors went on to state, “The study is also of interest scientifically because under the hypothesized mechanisms, an every other day dose was not thought to be adequate for cancer prevention.”
Cook mentioned, “In terms of recommendations for aspirin in the general population, there are many risks and benefits that need to be weighed.” While aspirin appears to be beneficial in colorectal cancer and cardiovascular disease, it also has adverse effects. Some of these effects are serious, such as hemorrhagic stroke and gastrointestinal hemorrhage, although these are rare, and some are less serious, such as peptic ulcers. The authors concluded, “Aspirin may not be right for most people, but those at high risk for heart disease or colorectal cancer may want to consider taking it. Each person should discuss with their doctor whether taking aspirin would be right for them.”
– Written by Hannah Branch
Source: Cook NR, Lee I-M, Zhang SM, Moorthy MV, Buring JE. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann. Intern. Med. 159(2), 77–85 (2013).
Molecular, genetic test could detect fetal trisomies earlier in pregnancy
PrenaTest® (LifeCodexx, Konstanz, Germany) is the first noninvasive molecular genetic blood test in Europe that identifies fetal trisomies 13, 18 and 21 in maternal blood using next-generation sequencing techniques. This test can now be implemented in high-risk pregnancies after week 9. It may be advised that PrenaTest is performed at this stage of the pregnancy if there is a high risk of the child developing such a trisomy owing to a genetic disposition.
The new, early detection ability of PrenaTest was achieved through advances in QuantYfeX™ technology, which is used by LifeCodexx to measure cell-free fetal DNA (cffNA) in maternal blood at the start of the laboratory process. In the event of at least 4% cffDNA being present in early pregnancy, LifeCodexx can effectively analyze the blood sample. In addition, this technology also allows the physician to be alerted if the amount of cffDNA is too low, at the start of the laboratory process. This, in turn, allows the physician to quickly take a new sample of blood and minimize the waiting period for the mother.
Along with its collaborative partner Sequenom Inc. (CA, USA), LifeCodexx conducted further clinical validation of PrenaTest. This was done using 340 samples from women known to have risk pregnancies. This study demonstrated that the test had an overall detection rate of 100%. Furthermore, based on the total collective 808 clinical samples, a total of 99.8% samples could be accurately diagnosed.
In their press release, Michael Lutz, Chairman at LifeCodexx AG, stated, “Through the advancement of our QuantYfeX technology and its early integration into the PrenaTest analysis, we are the first company worldwide that is able to notify physicians and their respective patients immediately on accession of the sample, if the blood sample can be analyzed.” Wera Hofmann (Medical Director at LifeCodexx AG) added, “The attending physician will decide during consultation of the patient, if the improved PrenaTest is advisable before the ninth week of pregnancy.” Furthermore, Hofmann stated, “According to the recommendations of experts, noninvasive molecular genetic tests such as PrenaTest are especially advisable in connection with a first trimester ultrasound.”
To date, approximately 4000 women have opted for PrenaTest. It is concluded that less than 0.2% of samples could not be analyzed successfully regardless of the occurrence of a requested repeat test. Finally, at present, PrenaTest is available in a number of countries across Asia, Europe and the Middle East.
– Written by Hannah Branch
Source: LifeCodexx press release. Improved PrenaTest® provides early knowledge for high risk pregnancies: www.b3cnewswire.com/20130710926/improved-prenatestr-provides-early-knowledge-for-high-risk-pregnancies.html
Researchers analyze infertility and time to pregnancy in female cancer survivors
Past research has demonstrated lower pregnancy rates and early menopause in female who have survived cancer. Despite this, infertility rates and reproductive interventions have yet to be analyzed. Recently, Sara Barton (Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA) and coworkers looked at female childhood cancer survivors to investigate infertility and time to pregnancy. The group also studied treatment characteristics that are linked to infertility and subsequent pregnancy.
The research, published in a recent issue of Lancet Oncology, involved the Childhood Cancer Survivor Study (CCSS). This is a cohort study “including 5-year cancer survivors from 26 Canadian and US institutions who were younger than 21 years at the time of diagnosis between 1 January 1970 and 31 December 1986, and a sibling control group.” The group included women aged 18–39 years old who had ever been sexually active.
The group “gathered demographic, medical, and reproductive data via a baseline questionnaire, and quantified exposure to alkylating agents and radiation therapy.” In addition, they analyzed self-reported infertility, medical infertility therapy, time to first pregnancy in both cancer survivors and siblings as well as the risk of infertility in survivors “by demographic, disease and treatment variables.”
The study included 3531 cancer survivors and 1366 female sibling controls who enrolled between November 1992 and April 2004. The group noted, “Compared with their siblings, survivors had an increased risk of clinical infertility (i.e., >1 year of attempts at conception without success), which was most pronounced at early reproductive ages.” Although the likelihood of seeking infertility treatment was equal, cancer survivors were less likely to be prescribed drugs for infertility treatment than their siblings.
The group stated, “Increasing doses of uterine radiation and alkylating agent chemotherapy were strongly associated with infertility.” Furthermore, despite the cancer survivors having an increased time to pregnancy as compared with their siblings, 64% of 455 participants who had self-reported clinical infertility achieved a pregnancy.
The results of this study led the authors to comment, “A more comprehensive understanding of infertility after cancer is crucial for counseling and decision-making about future conception attempts and fertility preservation.”
– Written by Hannah Branch
Source: Barton SE, Najita JS, Ginsburg ES et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 14(9), 873–881 (2013).
Seafood consumption could be related to anxiety levels in pregnancy
There is not a vast amount known regarding the associations between significant anxiety in pregnancy, dietary patterns and n-3 polyunsaturated fatty acids (PUFAs). Consequently, in a recent study published in PLoS ONE, Juliana dos Santos Vaz (Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil) and colleagues aimed to investigate whether dietary patterns and n-3 PUFA intake from seafood is linked with excessive anxiety during pregnancy.
In 1991–1992, the group enrolled 9530 pregnant women in the Avon Longitudinal Study of Parents and Children (ALSPAC). They employed a food frequency questionnaire with principal component analysis to determine dietary patterns. Furthermore, the group also analyzed the total n-3 PUFA intake from seafood. The researchers then measured anxiety symptoms at 32 weeks gestation using the Crown–Crisp Experimental Index whereby scores greater than or equal to nine corresponding to the 85th percentile were classed as high anxiety symptoms. To estimate the odds ratio and 95% CI, multivariate logistic regression models were used, adjusted by lifestyle and socioeconomic variables.
“… the study suggests that a technique to reduce excessive anxiety symptoms in pregnancy could involve dietary interventions.”
The multivariate results demonstrated, “women in the highest tertile of the health-conscious and the traditional pattern scores were less likely to report high levels of anxiety symptoms.” Whereas, women who were in the highest tertile of the vegetarian pattern score “were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood when compared with those with intake of >1.5 g/week.”
Taken together, the outcomes of this research support the idea that there is a relationship between “dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy.” Furthermore, the study suggests that a technique to reduce excessive anxiety symptoms in pregnancy could involve dietary interventions.
– Written by Hannah Branch
Source: Vaz Jdos S, Kac G, Emmett P, Davis JM, Golding J, Hibbeln JR. Dietary patterns, n-3 fatty acids intake from seafood and high levels of anxiety symptoms during pregnancy: findings from the Avon Longitudinal Study of Parents and Children. PLoS ONE 8(7), e67671 (2013).
Elucidating the potential association between women's height and cancer risk
There have been suggestions from some western and Asian prospective studies that height may be a risk factor for a variety of cancers. Despite this, few investigations have looked into possible confounding or effect modification of the potential relationship by other factors. Subsequently, Geoffrey Kabat (Albert Einstein College of Medicine, NY, USA) and colleagues chose to examine the possible link between height and cancer risk.
Cancer Epidemiology, Biomarkers and Prevention recently published the research whereby the group analyzed the potential correlation between the heights of 144,701 women upon enrolment to participate in the Women's Health Initiative and “the risk of all cancers combined and cancer at 19 specific sites.” The median follow-up period of the study was 12 years and in this time, 20,928 incident cancers were observed. The researchers then employed Cox proportional hazards models to determine estimated hazard ratio and “95% CI per 10 cm increase in height, with adjustment for established risk factors.” In addition, the group analyzed the possible effect modification of the association with all and specific cancers.
The published work indicates “Height was significantly positively associated with risk of all cancers as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary and breast, and with multiple myeloma and melanoma.” These associations appeared generally insensitive to adjustment for confounders. Furthermore, there seemed to be little evidence of effect modification.
Taken together, the results of this study lend support to the presence of a “positive association of height with risk of all cancers and a substantial number of cancer sites.” The authors of this study finally noted, “Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association.”
– Written by Hannah Branch
Source: Kabat GC, Anderson ML, Heo M et al. Adult stature and risk of cancer at different anatomic sites in a cohort of postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 22(8), 1353–1363 (2013).
Innovative molecule may target metabolism-dependent growth in breast cancer
Uncovering new ways of targeting and treating refractory breast tumors is a key challenge in cancer research. “To overcome this resistance, innovative treatments that use new approaches to stop cancer from growing are desperately needed,” explains Jeremy Blaydes of the University of Southampton (Southampton, UK). Research by Blaydes and colleagues, published recently in Chemical Science, may have identified once such innovative way of targeting the growth of malignant cells.
The metabolism of cancer cells is distinct when compared to that of healthy cells; these tumor cells disseminating and utilizing their energy supplies in a different manner. In malignant cells some proteins are metabolically regulated and in breast cancer cells, one such protein is C-terminal binding protein (CtBP). CtBPs depend upon a product of metabolism termed NADH to catalyze their dimerization and activation. Once dimerized, these proteins form complexes that have a chromtin-modifying, and therefore a transcriptional, impact on many genes, which in turn has a significant impact on cell proliferation, survival and migration.
“This work is … really exciting as it has the potential to deliver a completely new kind of cancer drug.”
The team postulated that blocking this metabolically driven activation of CtBPs might have an impact on tumor cell growth, and so using a technique known as high-throughput screening they looked at millions of cyclic peptides in an attempt to identify a suitable inhibitor. They identified several potential inhibitors, the most effective being CP61. When administered to breast cancer cell lines with high metabolic activity, CP61 was found to reduce their proliferative and colonyforming abilities. The team is now working to develop the inhibitor into a druggable form.
“What makes this discovery even more exciting as a potential treatment is that CtBPs are mostly only active in the cancer cells, so blocking this ‘sweet tooth’ should cause less damage to normal cells and fewer side effects than existing treatments. This work is at an early stage in the laboratory but it is really exciting as it has the potential to deliver a completely new kind of cancer drug,” added Blaydes.
– Written by Emily Brown
Sources: Birts CN, Nijjar SK, Mardle CA et al. A cyclic peptide inhibitor of C-terminal binding protein dimerization links metabolism with mitotic fidelity in breast cancer cells. Chem. Sci. doi:10.1039/C3SC50481F (2013) (Epub ahead of print); University of Southampton press release: www.southampton.ac.uk/mediacentre/news/2013/aug/13_146.shtml
Milky spot colonization by ovarian cancer cells influences metastases
A study by researchers from The University of Chicago (IL, USA) has suggested a method for which ovarian cancer cells colonize the abdominal cavity, particularly the omentum, a phenomenon that is of large interest in cancer research.
The omentum is a large peritoneum that encloses the abdominal organs. Deciphering this mystery could lead to better management and/or prevention of ovarian cancer. The omentum comprises of adipocytes, blood vessels and immune cells, among others, as well as immune cell-containing structures termed ‘milky spots’, which are fundamental to protection.
Milky spots and adipocytes have been the main focus of research, which suggests that they play a key role in attracting metastatic ovarian cancer cells. However, Carrie Rinker-Schaeffer, a researcher involved in the study, to be published in The American Journal of Pathology, commented: “Although there are clear strengths to both of these models, neither address the intimate and dynamic interaction among milky spots, surrounding adipocytes, and other components of omental tissues. We propose an alternative, more fully integrated model.”
By exploiting the fact that mice have a secondary source of abdominal fat containing milky spots (splenoportal fat), as well as fat lacking in milky spots (gonadal, uterine and mesenteric fat), research was undertaken to investigate whether fat tissue in the abdomen containing milky spots was a more attractive target for cancer cells than tissue that does not contain milky spots. They discovered that different ovarian cancer cell lines specifically target omental and splenoportal fat, whereas ovarian cancer cells are rarely found in fat lacking milky spots. Large lesions of cancer cells within these milky spots were found.
Further experiments showed that tissues containing milky spots secrete factors that attract cancer cells to the structure and, in particular, they are able to condition cell growth medium to stimulate cancer cell migration. A 95-fold increase in cell migration was discovered in cell medium-conditioned omenta and splenoportal fat compared with controls. The researchers also showed, by using immunodeficient mice, that colonization of milky spots by ovarian cancer cells is not affected in the absence of immune cells such as T, B or natural killer cells.
An inverse relationship between ovarian cancer cell growth and depletion of adipotcytes was also demonstrated in the study. “These data are consistent with previous reports from other investigators that indicate cancer cells use lipids stored in adipocytes as an energy source for their continued growth,” explained Rinker-Schaeffer. “Certain tumor cells (the ‘seed’) have a proclivity for specific organ microenvironments (the ‘soil’).” She concludes: “Pioneers of metastasis research appreciated that the unique tissue architecture, physiology, and function of the target organ are essential to understanding metastatic organ specificity. With this in mind, we hope that our findings and discussion of how they fit into the big picture of omental colonization will facilitate studies that continue to improve our understanding of this process.”
– Written by Janet Lee
Source: Elsevier press release: www.elsevier.com/about/press-releases/research-and-journals/ovarian-cancer-metastases-influenced-by-factors-in-target-tissues
In brief…
A recent study aimed to evaluate chronic hypertension (CH), perceived lifetime stress and perceived stress during pregnancy and their relation to pre-eclampsia. The study monitored 4314 women at Boston Medical Center (MA, USA) delivering singleton live births from October 1998 through to February 2008. CH was classed as hypertension diagnosed prepregnancy; in addition, lifetime and perceived stress information was collected using a questionnaire. The results indicated that both CH and psychosocial stress act together to increase the risk of pre-eclampsia, with patients with both at a 20-fold greater risk. Overall, this trial demonstrates the need for prevention, screening and management of CH, and reduce psychosocial stress, principally in women with CH.
About the Bulletin Board
The Bulletin Board highlights some of the most important events and research in the field of women's health. If you have newsworthy information, please contact:
Hannah Branch, Commissioning Editor, Women's Health, Future Medicine Ltd,