paywalled: Phenotype and Polyp Landscape in Serrated Polyposis Syndrome: A Series of 100 Patients From Genetics Clinics (Lynch Syndrome...)

 define: hyperplastic

hyperplastic colon polyps

What is a hyperplastic colon polyp?

                    ~~~~~~~~~~~~~~~~~~~~~~~~~~

Phenotype and Polyp Landscape in Serrated Polyposis Syndrome: A Series of 100 Patients From Genetics Clinics

Abstract

Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large intestine and associated with an increased risk of colorectal cancer (CRC). There are a variety of SPS presentations, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in patients with SPS recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada, and the United States. Three specialist gastrointestinal pathologists reviewed the polyps, which they classified into conventional adenomas or serrated polyps, with various subtypes, according to the current World Health Organization criteria. Mutations in BRAF and KRAS and mismatch repair protein expression were determined in a subset of polyps. A total of 100 patients were selected for the study, of whom 58 were female and 42 were male. The total polyp count per patient ranged from 6 to 150 (median 30). The vast majority of patients (89%) had polyposis affecting the entire large intestine. From this cohort, 406 polyps were reviewed. Most of the polyps (83%) were serrated polyps: microvesicular hyperplastic polyps (HP) (n=156), goblet cell HP (n=25), sessile serrated adenoma/polyps (SSA/P) (n=110), SSA/P with cytologic dysplasia (n=28), and traditional serrated adenomas (n=18). A further 69 polyps were conventional adenomas. BRAF mutation was mainly detected in SSA/P with dysplasia (95%), SSA/P (85%), microvesicular HP (76%), and traditional serrated adenoma (54%), whereas KRAS mutation was present mainly in goblet cell HP (50%) and in tubulovillous adenoma (45%). Four of 6 SSA/Ps with high-grade dysplasia showed loss of MLH1/PMS2 expression. CRC was diagnosed in 39 patients who were more often found to have a conventional adenoma compared with patients without CRC (P=0.003). Patients with SPS referred to genetics clinics had a pancolonic disease with a high polyp burden and a high rate of BRAF mutation. The occurrence of CRC was associated with the presence of conventional adenoma.

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.:

Study
Breast Cancer Res Treat. 2012 Mar 21;

Abstract

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations.

Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8 %. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77 % of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16 %).

Median age of onset for mutation carriers was 39 years. (?? Blogger's Note: screening guidelines...)  Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36 %) had a BRCA1 mutation, while 27 % of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48 % (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer.

It is noteworthy, however, that of the 65 carriers, 15 (23 %) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98 %). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

abstract: Anthropometric Measures (BMI, height, weight gain) and Risk of Ovarian Cancer Among BRCA1 and BRCA2 Mutation Carriers

"....Height, weight, and BMI were not associated with the risk of ovarian cancer (P-trend ≥0.15). Also, there was no association between changes in body weight between ages 18-30, or ages 30-40, or ages 18-40 and the risk of ovarian cancer (P-trend ≥0.28). The results from this study suggest that height, weight, or weight gain do not influence the risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation."

Risks - When Too Much Vitamin D Is Too Much - NYTimes.com

references Johns Hopkins University study  published in The American Journal of Cardiology.

open access: Jan 2012 - Assessing the malignant potential of ovarian inclusion cysts in postmenopausal women within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a prospective cohort study

Objective  To evaluate the malignant potential of ultrasound-detected ovarian inclusion cysts in the development of ovarian cancer (OC) in postmenopausal women.

Design  Prospective cohort study.

Setting  UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Population  Postmenopausal women.

Conclusions  Postmenopausal women with ultrasound-detected inclusion cysts do not seem to be at increased risk of ovarian or breast/endometrial (hormone-dependent) cancers.

see also 

Table 1.   Details of ovarian cancers detected in the cohort of women with inclusion cysts in year 1 

Table 2.   Details of ovarian cancers detected in the cohort of women with normal scans in year 1 

Table 3.   Relative risks of developing gynaecological cancers in women with inclusion cysts

open access: BMJ - Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm | BMJ

Objective 

To derive and validate an algorithm to estimate the absolute risk of having ovarian cancer in women with and without symptoms.

Main outcome The primary outcome was incident diagnosis of ovarian cancer recorded in the next two years.

The incidence rate in our population was higher than published national data based on cancer registries.2

What is already known on this topic

• Ovarian cancer is the second most common gynaecological cancer and most women are diagnosed with late stage disease, which has a poor survival rate
• Earlier diagnosis could improve with more targeted investigation of symptomatic patients and increased public awareness of symptoms, which is a major challenge given the non-specific nature of some of the symptoms

What this study adds

• An algorithm based on simple clinical variables such as age, family history of ovarian cancer, anaemia, abdominal pain, abdominal distension, rectal bleeding, postmenopausal bleeding, appetite loss, and weight loss, which the patient is likely to know or which are routinely recorded in general practice computer systems, can estimate absolute risk of ovarian cancer in women with and without symptoms in primary care
• The algorithm could be integrated into general practice clinical computer systems and used to assess risk in women presenting with and without symptoms

full free access: Hormonal Contraception—What Kind, When, and for Whom?

Continuing Medical Education

Abstract

Method

Selective review of the literature.

Results

COCs suppress gonadotropin secretion and thereby inhibit follicular maturation and ovulation. Their correct use is associated with 0.3 pregnancies per 100 women per year, their typical use, with 1 pregnancy per 100 women per year (Pearl index). COCs have effects on the cardiovascular and hemostatic systems as well as on lipid and carbohydrate metabolism. When given in the presence of specific risk factors, they significantly increase the likelihood of cardiovascular disease and thromboembolism. Women with persistent human papilloma virus (HPV) infection who take COCs are at increased risk of developing invasive cervical cancer. On the other hand, COCs lower the cumulative incidence of endometrial and ovarian cancer by 30% to 50%, and that of colorectal cancer by 20% to 30%. Other malignancies seem to be unaffected by COC use.

Conclusion

As long as personal and familial risk factors are carefully considered, COCs constitute a safe, reversible, and well-tolerated method of contraception.

Most women carrying cancer genes (BRCA 1/2) take action: study | Reuters

Breast density 'linked to specific types of breast cancer' | International Federation of Gynecology and Obstetrics

"Given that the magnitude of the association with breast density is strong across all breast cancer subtypes and particularly for [oestrogen receptor]-negative disease, breast density should be included in risk prediction models across tumour subtypes," the researchers said.

abstract - Ovarian cancer risk assessment (OCRA): a tool for preoperative assessment

Objectives

The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses.

 Highlights

► Correct pre-operative diagnosis of ovarian cancer is key to referral.
► Surgery by gynecologic oncologist helps survival.
► Combination of age, prealbumin, CA 125 helps proper referral.

The Numbers Game: The Risky Business of Projecting Risk (response/reference breast cancer paper)

Note: worth paying attention to the stats

News - Women’s Height Is Linked to Cancer Risk, Say Researchers

Full text: The relative risk of second primary cancers: a retrospective cohort study

"Within the female cohort, the relative risk of a second cancer was higher for those diagnosed with head and neck cancer, colorectal cancer, lung cancer, melanoma, breast cancer, cervical cancer, uterine cancer, kidney cancer, bladder cancer, thyroid cancer, non-Hodgkin lymphoma, lymphoid leukaemia or myeloid leukaemia.

There were no types of cancer for which female survivors had a significantly lower risk of developing a second invasive cancer (see references to male cancers and lower risk) in relation to the general population."

Table 4. Relative risk of second primary cancer by type of first primary cancer and time period of first diagnosis, Queensland, 1982-2006

What's My Risk? | Cancer Risk Tool from OncoLink - questionnaire

HRT Post Oophorectomy Adds No Breast Cancer Risk : Internal Medicine News

"....The PROSE database was developed by 20 centers in the United States and Europe who identified and prospectively followed women with a deleterious BRCA1 or BRCA2 mutation. For the study, the investigators focused on those who at ascertainment had at least one ovary, no prior breast or ovarian cancer, no prior bilateral mastectomy, and at least 6 months of follow-up. ...."

extract: Cancer Risk Assessment in Lynch Syndrome, June 8, 2011 — JAMA

Genetic variants associated with breast-cancer risk : The Lancet Oncology (Steven A Narod)

Note: register (free) to view

abstract: Rotating night shift work and risk of ovarian cancer

Conclusions: In this large prospective study, there was no association between duration of rotating night shift work and risk of ovarian cancer.
Impact: Although associated with other cancers, night shift work does not appear to be associated with increased risk of ovarian cancer. However, further exploration of the association between melatonin and risk of ovarian cancer is warranted.

Lynch Syndrome Hereditary Cancers Public Awareness Day | Fight Colorectal Cancer

Increased Risk of Cancer

If a parent carries a Lynch mutation there is a 50-50 chance that their child will inherit Lynch syndrome with

• 60 to 80 percent increased lifetime risk of colorectal cancer.
• 40 to 70 percent increased risk of endometrial cancer (cancer of the uterus lining).
• 13 percent increased risk for stomach cancer
• 12 percent increased risk of ovarian cancer.
• smaller, but significant risk of small intestine, urinary tract, heptobiliary (liver, gall bladder and bile ducts), skin, and brain cancers.
• Some families may also have increased risk for breast cancer.

Note: 
Lynch Syndrome is also noted for multiple primary cancers (different cancers in one person)

Women's Health - Full Text: Preventing familial breast and ovarian cancer: major research advances with little implication

Preventing familial breast and ovarian cancer: major research advances with little implication

Primary prevention of hereditary breast–ovarian cancer syndrome, which accounts for 5–10% of all breast cancer diagnosis, represents a prime paradigm of excellence of personalized medicine [1,2]. However, genetic testing can reveal that BRCA mutation carriers account for less than 25% of the familial risk. There has been little progress in explaining the missing heritability of the remaining 75% of women with family history who test negative for BRCA mutations. Neither recently identified common low-penetrance variants alone, nor their interactions with established environmental risk factors, are able to explain missing heritability. But even among BRCA mutation carriers, the decision by an expert scientific team for the optimal preventive strategy, choosing between prophylactic surgery and intensive surveillance, is very difficult and should be individualized for each woman. Here we discuss the latest advances in breast cancer genetics, their potential to impact prevention strategies and practices, and the future perspectives for a true personalized preventive medicine...........

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Previous work has suggested the polygenic model to help understand the 75% of breast cancer familial risk [6]. According to this model, the missing heritability could be explained by the accumulation of low to moderate genetic risk variants other than BRCA1/2 genes, namely BRCA3 or BRCA4 high-penetrance genes. Indeed, more than 15 years after the discovery of BRCA1/2 genes, the ‘classical’ linkage studies in high-risk families have identified no other high-penetrance genes. The completion of the HapMap 3 project with a database of common and rare variants [7] and high-throughput screening technology has allowed a new generation of association studies to provide improved understanding of the genetics of familial cancer.

Rare BRCA mutations	ChooseTop of pageRare BRCA mutations <<Missing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Missing heritability	ChooseTop of pageRare BRCA mutationsMissing heritability <<Genome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Genome-wide association studies	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s... <<Next generation of GWASWhole-genome ...Current practical prevent...ConclusionBiliography

Next generation of GWAS	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWAS <<Whole-genome ...Current practical prevent...ConclusionBiliography

Whole-genome & exome sequencing	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ... <<Current practical prevent...ConclusionBiliography

Current practical preventive approaches	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent... <<ConclusionBiliography

Conclusion	ChooseTop of pageRare BRCA mutationsMissing heritabilityGenome-wide association s...Next generation of GWASWhole-genome ...Current practical prevent...Conclusion <<Biliography