High Calcium may Flag Ovarian Cancer

Tuesday - January 29, 2013

Nick Tate

In a groundbreaking new study, researchers from Wake Forest Baptist Medical Center have found high blood calcium levels might flag ovarian cancer — the most lethal of the gynecologic cancers.

The finding, published online in the journal Gynecologic Oncology, could point the way to a new way to predict women who may be at greater risk of developing ovarian cancer, which is often diagnosed late when it is harder to treat.

Lead researcher Gary G. Schwartz, a cancer epidemiologist at Wake Forest Baptist, made the connection by examining associations between blood calcium and ovarian cancer in two groups of cancer patients. Schwartz and co-researcher Halcyon G. Skinner, of the University of Wisconsin Carbone Cancer Center, found women who were later diagnosed with ovarian cancer and women who later died of ovarian cancer had higher levels of calcium in their blood than women who did not before their cancer diagnosis.

Schwartz said the idea for this study sprung from earlier research that showed men with high calcium levels were at increased risk of aggressive prostate cancer. That led him to wonder if a similar relationship were true of ovarian cancer.

"One approach to cancer biomarker discovery is to identify a factor that is differentially expressed in individuals with and without cancer and to examine that factor's ability to detect cancer in an independent sample of individuals," Schwartz said.

"Everyone's got calcium and the body regulates it very tightly," Skinner added. "We know that some rare forms of ovarian cancer are associated with very high calcium, so it's worth considering whether more common ovarian cancers are associated with moderately high calcium."

The researchers explained that tumors in many cancers produce increased levels of a protein — known as PTRHrP (parathyroid hormone-related protein) — that raise calcium levels in blood.

The finding could be particularly significant for patients who develop types of cancer, such as ovarian cancer, that have high fatality rates because they are hard to detect early.

Schwartz said the findings could lead to the use of a calcium biomarker to diagnose ovarian cancer early, but noted more research is needed.

"We found the link between serum calcium and ovarian cancer; we confirmed it, and even though the study is small, we're reporting it because it's a very simple thing in theory to test," he said.
NewsMaxHealth

Role of heparan sulfatases in ovarian and breast cancer.

2013

Khurana A, Beleford D, He X, Chien J, Shridhar V.

Source

Department of Experimental Pathology, Mayo Clinic College of Medicine Rochester, MN, USA.

Abstract

Endosulfatases HSulf-1 and -2 (also referred to as Sulf1 and -2) represent a family of enzymes that modulate heparin binding growth factor signaling. Heparan sulfatase 1 (HSulf-1) and heparan sulfatase 2 (HSulf-2) are two important 6-O endosulfatases which remove or edit 6-O sulfate residues of N-glucosamine present on highly sulfated HS. Alteration of heparan sulfatases have been identified in the context of several cancer types. Many cancer types either exhibit increased or decreased HSulfs expression at the transcript levels. Specifically, HSulf-1 was found to be downregulated in early-stageovarian tumors, hepatocellular carcinoma, and metastatic breast cancer patients. HSulf-2 was found to be upregulated in ductal carcinoma in situ and invasive ductal carcinoma, whereas limited information is present about HSulf-2 expression in different stages of ovarian cancers. Here, we review the important role of these sulfatases play in ovarian and breast cancers in terms of tumorigenesis such as angiogenesis, chemoresistance, apoptosis, growth factor signaling, hypoxia and metastasis. These recent discoveries have added significant understanding about these sulfate editing enzymes.

PubMed

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals.

Jan 2013

Ma C, Liu Y, Zhang W, Liu P.

Source

Department of Gynecology, Changning Maternity and Infant Health Hospital of Shanghai, 773 Wuyi Road, Shanghai, 200051, China.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case-control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19-1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63-3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47-2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12-1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.

Springerlink

Breastfeeding babies can reduce a mother's risk of Ovarian cancer by two-thirds

By PAT HAGAN

PUBLISHED: 20:39 EST, 11 January 2013 | UPDATED: 20:39 EST, 11 January 2013

Breastfeeding her baby can reduce a mother’s risk of ovarian cancer by nearly two-thirds, according to scientists.

And the longer she continues to do it, the greater the protection against the illness.

The research adds to evidence of the benefits of natural feeding as numerous studies  have already shown it cuts the chance of  breast cancer.

More than 6,000 patients a year in the UK are diagnosed with ovarian cancer, and the illness accounts for about 5 per cent of cancer deaths in women.

It is known as the ‘silent killer’ because symptoms for many sufferers, such as feeling bloated, are non-specific and the illness may not be diagnosed until it is fairly advanced.

For the latest study, Australian scientists studied 493 women diagnosed with ovarian cancer and compared them with 472 healthy volunteers of similar age.

Each was asked how many children they had and for how long they breastfed each one.

The results showed those who breastfed a child for at least 13 months were 63 per cent less likely to develop a tumour than those who did so for less than seven months.

The more children they had, the greater the effect, said the findings, published in the American Journal of Clinical Nutrition. Mothers who had three children and breastfed for a total of 31 months or more were found to cut their chances of ovarian tumours by 91 per cent. This was compared to those feeding naturally for a total of under ten months.

Breastfeeding is thought to help as it delays ovulation, when eggs are released and the ovaries are exposed to high levels of oestrogen-rich fluid.

Some researchers believe a higher number of ovulations raises the risk of mutant cells forming, which can trigger the disease.

But surveys have shown the UK has one of the lowest breastfeeding rates in Europe.

Nearly eight in ten mothers start when their baby is born but after six weeks, this is down to half.

After six months – the recommended time for exclusive breastfeeding – it is only 26 per cent.

The main risk factors for ovarian cancer include a family history of the disease, having already had breast cancer, starting periods at a young age and being overweight.

Dr Helga Groll, of Cancer Research UK, said the findings backed up earlier evidence on the benefits of breastfeeding.

But she warned that some mothers may not accurately remember for how long they had breastfed.

Gilda Witte, chief executive of Ovarian Cancer Action, added: ‘It is proven that breastfeeding can reduce the risk of ovarian cancer.

‘It does this because it reduces ovulation for the nursing mother.

‘The risk is further reduced by each child that a woman bears.’

MailOnline

Pap Smear Detects Ovarian, Uterine Cancer

Pap Smear Detects Ovarian, Uterine Cancer

By: VICTORIA BRINKLEY | 

Published: January 11, 2013

MEDICAL WATCH --

A pap smear can be used to detect ovarian and uterine cancers, in addition to cervical cancer, according to a study published in Science Translational Medicine.

Scientists at Johns Hopkins used a cervical fluid, which is collected during a Pap smear, to do a genome sequencing called the PapGene.

More studies are needed.

Ovarian cancer is the deadliest form of cancer in women, partly because it's difficult to detect.

NewsChannel 12

Declining Second Primary Ovarian Cancer After First Primary Breast Cancer.

Jan 2013

Schonfeld SJ, de Gonzalez AB, Visvanathan K, Pfeiffer RM, Anderson WF.

Source

Sara J. Schonfeld, Amy Berrington de Gonzalez, Ruth M. Pfeiffer, and William F. Anderson, Department of Health and Human Services (DHHS), National Institutes of Health (NIH), National Cancer Institute, Bethesda; Kala Visvanathan, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Abstract

PURPOSE: Although ovarian cancer incidence rates have declined in the United States, less is known of ovarian cancer trends among survivors of breast cancer. Therefore, we examined second primary ovarian cancers after first primary breast cancer. 

METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results program (1973 to 2008). Standardized incidence ratios (SIRs) were calculated as the observed numbers of ovarian cancers among survivors of breast cancercompared with the expected numbers in the general population. Absolute rates were measured as the incidence rates for second primary ovarian cancer by year of diagnosis of the first primary breast cancer adjusted for age of breast cancerdiagnosis and years since diagnosis.

RESULTS: SIRs for second primary ovarian cancer were elevated over the entire study period (SIR, 1.24; 95% CI, 1.2 to 1.3), whereas the absolute rates declined with an estimated annual percentage change near 1% (-1.34% to -0.09% per year). Secular trends for second ovarian cancers were similar after estrogen receptor (ER) -positive and ER-negative breast cancers, whereas the age-specific patterns varied significantly by ER expression (P for interaction < .001). The largest SIR was among w

CONCLUSION: Persistently elevated SIRs along with decreasing absolute rates over the entire study period suggest that ovarian cancers in both the general population and survivors of breast cancer are declining in parallel, possibly because of common risk factor exposures. Analytic studies are needed to further assess the parallel overall trends and the age-specific interaction by ER expression.

Full Text Article

Journal of Clinical Oncology

Targeting GRB7/ERK/FOXM1 Signaling Pathway Impairs Aggressiveness of Ovarian Cancer Cells.

2012

Chan DW, Hui WW, Cai PC, Liu MX, Yung MM, Mak CS, Leung TH, Chan KK, Ngan HY.

Source

Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R.China.

Abstract

Ovarian cancer is a highly lethal disease with poor prognosis and especially in high-grade tumor. Emerging evidence has reported that aberrant upregulation and activation of GRB7, ERK as well as FOXM1 are closely associated with aggresivenesss of human cancers. However, the interplay between these factors in the pathogenesis of human cancers still remains unclear. In this study, we found that GRB7, ERK phosphorylation  and FOXM1 were frequently increased and associated with high-grade tumors, as well as a high tendency in association with advanced stage ovarian cancer by immunohistochemical analysis. Intriguingly, the expressions of GRB7 , ERK phosphorylation  and FOXM1 showed a significant stepwise increase pattern along Grade 1 to Grade 3ovarian cancers. Biochemical studies using western blot analysis demonstrated that enforced expression or knockdown of GRB7 showed GRB7 could elevate the levels of ERK phosphorylation and FOXM1, whereas enforced expression of FOXM1 could not alter levels of GRB7 and ERK phosphorylation. But inhibition of ERK signaling by U0126 or PD98059 could reduce the level of FOXM1 in GRB7-overexpressing ovarian cancer cells, suggesting that GRB7, ERK and FOXM1 are regulated orderly. Moreover, inhibition of ERK activity by U0126 or PD98059, or decreased FOXM1 expression by Thiostrepton significantly inhibited cell migration/invasion, tumor growth in vitro and in vivo. Collectively, our findings confer that targeting GRB7/ERK/FOXM1 signaling cascade may be a promising molecular therapeutic choice in combating ovarian cancer.

Full text article

PLOS

Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population.

2013

Laraqui A, Uhrhammer N, Lahlou-Amine I, El Rhaffouli H, El Baghdadi J, Dehayni M, Moussaoui RD, Ichou M, Sbitti Y, Al Bouzidi A, Amzazi S, Bignon YJ.

Source

1. Laboratoire de Recherche et de Biosécurité P3, Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc; ; 7. Laboratoires de Biochimie -Immunologie, Maroc, Université Mohammed V-Agdal, Faculté des Sciences de Rabat, Maroc.

Abstract

Worldwide variation in the distribution of BRCA mutations is well recognised, and for the Moroccan population no comprehensive studies about BRCA mutation spectra or frequencies have been published. We therefore performed mutation analysis of the BRCA1 gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for BRCA testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the BRCA1 gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years) were found to be associated with BRCA1 mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T), and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in BRCA1, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of BRCA2 in BC in Morocco is also under study. Our study is the first molecular investigation of the role of the BRCA genes in breast and ovarian cancer in Morocco.

PubMed

Angiogenesis Inhibitors in the Treatment of Epithelial Ovarian Cancer.

Jan 2013

Han ES, Wakabayashi M, Leong L.

Source

Department of Surgery, Division of Gynecologic Oncology, City of Hope, 1500 E. Duarte Road, Duarte, CA, 91010, USA, ehan@coh.org.

Abstract

OPINION STATEMENT: Treatment of epithelial ovarian cancer involves surgical management with staging or debulking surgery and chemotherapy with a platinum and taxane-containing regimen. Despite achieving a 70-80 % complete remission, patients often will recur. Novel therapies are needed to improve the treatment of ovarian cancers. Tumor angiogenesis is a critical process involved in the growth and metastasis of ovarian cancer. Numerous phase II trials with angiogenesis inhibitors have been reported and have led to the development and completion of several recent phase III trials in both upfront and recurrent ovarian cancers. Future studies will need to focus on how and when to incorporate angiogenesis inhibitors in the treatment armamentarium for ovarian cancers.

PubMed

Paulinda Schimmel Babbini: Raising ovarian cancer awareness

BY KYLIE JANE WAKEFIELD

Jan 2013

Often, when someone is coping with an extraordinary loss, the feelings can be all-encompassing. When Paulinda Schimmel Babbini’s daughter, Robin, died of ovarian cancer at the age of 20, instead of letting the tragic death immobilize her, Babbini made it her mission that no one else should go through what she had.

Babbini is the founder and president of The Ovarian Cancer Circle, a foundation she started in 2010 in memory of her daughter. In 2004, Robin, at age 16, was homecoming queen and co-captain of the cheerleading squad at Pacific Hills High School. That same year she also started complaining of cramps. Doctors brushed it off, saying it was her menstrual cycle. The symptoms persisted, however, and a year later she was diagnosed with stage-three ovarian cancer. Robin underwent a hysterectomy and chemotherapy treatments, and was able to enter into her first year of college at University of California, Santa Barbara. Six months later, the cancer recurred; she lost her tumultuous battle in 2006. 

Since its founding, the nonprofit Ovarian Cancer Circle, which includes 12 members, has raised more than $35,000 to fight ovarian cancer. 

“My focus for starting The Circle is to give ovarian cancer a higher public profile; to support research, educate, heighten awareness to the signs and symptoms of this cancer; and to raise funds for an early-detection test, which does not yet exist,” Babbini said. “So many lives are saved by mammograms, Pap smears and PSA tests [for prostate cancer]. But ovarian cancer is a stealth cancer, almost hidden, with few, and random, symptoms.” They are abdominal pressure, bloating, nausea, indigestion, feeling full but eating less, urinary frequency and constipation, she said. “Knowledge is critically important. I encourage women to pay attention to their bodies, know the symptoms and go to the gynecologist.”

Her group holds fundraisers twice a year and participates in numerous health fairs. They’ve hosted events at Hamburger Mary’s, featuring drag-queen bingo, along with a stand-up show at The Comedy Store in West Hollywood that showcased Sinbad as the headliner. On Feb. 21 at 11:30 a.m., Ovarian Cancer Circle is putting together a luncheon at Ruth’s Chris Steak House in Woodland Hills. The group will donate 100 percent of the proceeds to ovarian cancer research. On the Web site, theovariancancercircle.org, donations can be made by purchasing bracelets, scarves and necklaces in teal, the color designated to represent ovarian cancer, at Robin’s Store. 

Dalia Hayon, a friend, said she admires Paulinda for her strength and giving demeanor. “As a mother and grandmother, I would not have been able to bear the pain. It takes a special person and a mensch to be able to put aside her suffering, [to] be such an advocate for her girl and make sure other people are aware of it and know more about what to expect. She wasn’t expecting to get, but to give. She is a very giving person.”

For her part, Babbini said everything she does is in memory of her daughter. “Robin is my inspiration, motivation and strength. Her spirit inspires me to stay focused and, with steadfast determination, make a difference.”

Jewish Journal