Occupational cancer in Britain - ovarian, breast and cervical

Occupational cancer in Britain

"The following paper reviews the three cancers in women: breast, cervical and ovarian. There is no overlap between the cancers and exposure circumstances, and thus all are considered and described separately. Data for male breast cancer are much more limited and will not be considered here."

March 2011: Hereditary Cancer in Clinical Practice | Full text | Lynch Syndrome - is breast cancer a feature?

Background

The debate on whether or not breast cancer is in the tumor spectrum for Lynch syndrome produces a conundrum for healthcare providers.

The classic tumor spectrum for Lynch Syndrome (LS) includes colon, endometrial, ovarian, stomach, small intestine, hepatobiliary, urinary tract and brain/central nervous system cancers. Muir-Torre Syndrome (MTS) is a variant of LS that is associated with additional skin lesions including sebaceous gland tumors and keratoacanthomas. MTS was observed in 28% of LS families when assessing for MTS skin lesions [1]. It has also been reported that 10-14% of individuals with MTS present initially with breast cancer [2,3]. An extensive study published in 2002 excluded breast cancer as part of the tumor spectrum associated with LS [4].

However, more recently it was reported that DNA mismatch repair (MMR) gene deficiencies were identified in 51% of breast cancers arising in MMR mutation carriers [5]. Another study reported a male with an MLH1 mutation who had both colon and breast cancer. The breast cancer exhibited somatic reduction to homozygosity for the MLH1 mutation [6].

Here we report two unrelated families in which the proband has a germline MMR gene mutation and bilateral breast cancer, and one family in which the proband had ovarian and renal cancer and her daughter, maternal aunt and cousin had breast cancer at age 47, 59, and 48 respectively.

This raises the question are these breast cancers associated with the MMR mutations or a breast cancer susceptibility gene and what testing should be offered?

Conclusion

Our findings indicate that breast cancer is part of the spectrum of tumors in LS families in which the breast cancer segregates with the other LS associated tumors.

Additional hereditary breast cancer gene testing may not be warranted in these circumstances. A future research goal is to perform IHC on the breast tumors from these families to determine if they show loss of expression of the MMR gene that is known to be altered.

....cont'd (full free access)

full free access (pdf) A nomogram for estimating the probability of ovarian cancer

Note:  see Table 1       Distribution of age in years, morphology index ultrasound score, and serum CA125 level among patients with benign and malignant adnexal masses

Objective

Accurate preoperative estimates of the probability of malignancy in women with adnexal masses are essential for ensuring optimal care. This study presents a new statistical model for combining predictive information and a graphic decision support tool for calculating risk of malignancy.

Research Highlights

►This study presents a statistical model for measuring probability of ovarian cancer.
►Model includes age, ultrasound score, CA125 value, and nonlinearity adjustments.
►Excellent discrimination and calibration are obtained across the probability range.

"The nomogram developed in this study is not ready for clinical use, because it reflects the experience of a single institution. Further research using data from multiple institutions is required to develop a final model. However, these results demonstrate that accounting for non-linearity in the effects of age and CA125 yields better estimates of malignancy risk. Utilization of similar models in the treatment decision making process could reduce unnecessary referrals and increase appropriate referrals for women with masses identified pre-operatively as suspicious for malignancy."

full free access: The relative risk of second primary cancers in Queensland, Australia: a retrospective cohort study

full free access: Sex Hormones and Colorectal Cancer: What Have We Learned So Far? — J. Natl. Cancer Inst.

Increased risk of other cancers for relatives of women with early onset breast cancer | e! Science News

Published: Wednesday, September 29, 2010 - 18:23 in Health & Medicine

 

Close relatives of women diagnosed with breast cancer before the age of 35 years are at an increased risk of developing other cancers, according to a University of Melbourne study, published in the British Journal of Cancer today. Professor John Hopper, Director of Research from the Centre for Molecular, Environmental, Genetic and Analytic Epidemiology at the University of Melbourne, Australia, a lead investigator in the study, said these are surprising and novel findings which could be pointing to the existence of a new cancer genetic syndrome.
"The results suggest there could possibly be undiscovered genes causing breast cancer in these young women, and perhaps other cancers in their families," Professor Hopper said.
Every year in Australia, more than 300 women are diagnosed with breast cancer before the age of 35 years. This is approximately one in 40 of all breast cancers.
In the largest population based study of its kind, scientists studied 2200 parents and siblings of 500 women diagnosed with breast cancer before the age of 35 from across three countries, Australia, Canada and the United States.
After excluding families with mutations in BRCA1 and BRCA2, the two known major breast cancer susceptibility genes, they found that close relatives were at increased risk of not only breast cancer, but also of cancers of the prostate, lung, brain and urinary tract.

The results showed:

• Fathers and brothers had a 5-fold increased risk of prostate cancer.
• Mothers and sisters had a 2-fold increased risk of ovarian cancer as well as a 4-fold increased risk of breast cancer
• Close relatives also had a 3-fold increased risk for brain cancer, an 8-fold increased risk for lung cancer, and a 4-fold increased risk for urinary tract cancers.

"We wanted to find out what caused the early onset of breast cancer in these women and found some results we weren't expecting regarding their relatives," Professor Hopper said.
"The results of this study could help scientists discover new cancer susceptibility genes that explain the risk of early-onset and other cancers within some families," he said.
"Our next step is to conduct larger studies to further clarify these results."

Longer HRT Duration Tied to Lower Colon Cancer Risk

"It is possible that widespread use of HRT is partially responsible for the reductions that we have observed in distal large bowel cancer incidence over time," the authors write.

JCO: Lettter: Risk of Arterial Thrombosis Not Increased by Sorafenib or Sunitinib

Note: analyzing the research including a reference to Avastin

Assessing Women at High Risk of Breast Cancer: A Review of Risk Assessment Models: Abstract and Introduction

".......In addition to increasing the risks of breast and ovarian cancers, germline mutations in BRCA1 and BRCA2 are associated with an increased risk of prostate cancer and BRCA2 mutations are associated with increased risks of pancreatic and gastric cancers and melanoma.^[12] BRCA mutations tend to cluster within certain ethnic groups, such as Ashkenazi Jews,^[13–15] and in some populations, such as those in the Netherlands,^[16] Iceland,^[17,18] and Sweden.^[19] Germline mutations that are associated with familial breast cancer have been identified in other genes, including TP53, PTEN, ATM, CHEK2, NBS1, RAD50, BRIP, and PALB2, and others are suspected.^[20,21]"


Women who are at high risk of breast cancer can be offered more intensive surveillance or prophylactic measures, such as surgery or chemoprevention. Central to decisions regarding the level of prevention is accurate and individualized risk assessment. This review aims to distill the diverse literature and provide practicing clinicians with an overview of the available risk assessment methods. Risk assessments fall into two groups: the risk of carrying a mutation in a high-risk gene such as BRCA1 or BRCA2 and the risk of developing breast cancer with or without such a mutation. Knowledge of breast cancer risks, taken together with the risks and benefits of the intervention, is needed to choose an appropriate disease management strategy. A number of models have been developed for assessing these risks, but independent validation of such models has produced variable results. Some models are able to predict both mutation carriage risks and breast cancer risk; however, to date, all are limited by only moderate discriminatory accuracy. Further improvements in the knowledge of how to best integrate both new risk factors and newly discovered genetic variants into these models will allow clinicians to more accurately determine which women are most likely to develop breast cancer. These steady and incremental improvements in models will need to undergo revalidation....cont'd

A prospective study of dietary acrylamide intake and the risk of breast, endometrial, and ovarian cancers — Cancer Epidemiology, Biomarkers & Prevention

WHO website: What is acrylamide?

Abstract

Background
Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiological studies of acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk of breast, endometrial, and ovarian cancers in a prospective cohort study.

Methods
We assessed acrylamide intake among 88,672 women in the Nurses' Health Study using food frequency questionnaires administered every four years. Between 1980 and 2006 we identified 6301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk.

Results
We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk of endometrial cancer among high acrylamide consumers (adjusted relative risk [RR] for highest versus lowest quintile=1.41, 95% CI: 1.01-1.97, p-value for trend=0.03). We observed a non-significant suggestion of increased risk for ovarian cancer overall (RR 1.25, CI: 0.88-1.77, p-trend=0.12), with a significantly increased risk for serous tumors (RR 1.58, CI: 0.99-2.52, p-trend=0.04). Associations did not differ by smoking status.

Conclusions
We observed no association between acrylamide and breast cancer. Risk of endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers.

Impact
This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy.

How well can a screening test predict disease risk? « Genomes Unzipped

Characteristics and survival associated with ovarian cancer diagnosed as first cancer and ovarian cancer diagnosed subsequent to a previous cancer

Abstract

Objective:
To examine the risk of subsequent primary ovarian cancer among women diagnosed previously with cancer (subsequent cohort) and to compare demographic and tumor characteristics affecting overall survival of these women and women diagnosed with first primary ovarian cancer (index cohort).


Methods: 
We identified the two cohorts of women using the 1973-2005 Surveillance, Epidemiology and End Results (SEER) result data. We calculated relative risk of subsequent primary ovarian cancer and estimated 5-year risks of dying (hazard-ratios) after diagnosis of the first or subsequent primary ovarian cancer in the two cohorts, respectively using Cox modeling.


Results:
Women diagnosed with index cancers of the corpus uteri, colon, cervix, and melanoma at age younger than 50 had increased risk of ovarian cancer within 5 years after diagnosis (p<0.05); young breast cancer survivors had continued risk beyond 20 years. In 5-year follow-up survival analysis, the factors associated with a better survival (p<0.05) were similar in both cohorts and included more recent diagnosis; localized or regional disease; age <50 years at diagnosis; and being white versus black. A lower risk of dying from mucinous, endometrioid, or non-epithelial tumors than from serous was seen after 15 months (p<0.01), or after 32 months from diagnosis of the index and subsequent cohorts, respectively. (clear cell??)


Conclusions:
Age, stage, and histology affect ovarian cancer survival. The increased risk of ovarian cancer over time, especially among breast and colon cancer survivors who are less than 50 years of age, suggests common etiologies and necessitates careful surveillance by health care providers and increased survivors awareness through educational efforts.

Abstract: Red meat and colorectal cancer: a critical summary of prospective epidemiologic studies.

"Colinearity between red meat intake and other dietary factors (e.g. Western lifestyle, high intake of refined sugars and alcohol, low intake of fruits, vegetables and fibre) and behavioural factors (e.g. low physical activity, high smoking prevalence, high body mass index) limit the ability to analytically isolate the independent effects of red meat consumption. Because of these factors, the currently available epidemiologic evidence is not sufficient to support an independent positive association between red meat consumption and colorectal cancer."

Abstract: The role of body mass index, physical activity, and diet in colorectal cancer recurrence and survival: a review of the literature.

"In conclusion, only a paucity of data is available about the effect of dietary and other lifestyle factors on colorectal cancer recurrence and survival. Thus far, no clear conclusions can be drawn. Future studies are warranted, particularly on postdiagnosis BMI and diet."

Study Indicates Ginkgo biloba Does Not Reduce the Risk of Cancer [NCCAM Research Results]

Note: age specific/comments

full access: Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

"In eight out of 21 patients with bladder cancer, this was their first cancer diagnosis, whereas at this stage five of them developed another Lynch syndrome associated cancer at an older age. Therefore, early diagnosis of Lynch syndrome may prevent development of a second primary cancer..."

Recommendations for urothelial carcinomas surveillance in Lynch syndrome

1. Surveillance with a combination of ultrasound of the bladder and upper urinary tract, urinary cytology and sediment.
2. In every MSH2 mutation carrier
3. From age 40 and up
4. Performed every 1–2 years

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutation

Reminder on stats: < 1.0 is decreased risk; > 1.0 is increased risk; OR=overall risk; edited some stats for ease of reading - see abstract/read more:

Conclusions

Parity and oral contraceptive use are associated with reduced risks of fallopian tube cancer. In contrast, hormone replacement therapy may be associated with an increase in the risk of fallopian tube cancer.

Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: A meta-analysis

CONCLUSIONS: OC users carrying an ascertained BRCA1/2 mutation have a reduced risk of ovarian cancer, proportional to the duration of use. There is no evidence that recent OC formulations increase breast cancer risk in carriers

Menopausal hormone therapy and risk of colorectal cancer in the European prospective investigation into cancer and nutrition

"Our results show no significant association of estrogen-only or estrogen plus progestin therapy with colorectal cancer risk."

Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma

Note: this issue is important as early-age diagnoses in Lynch Syndrome is common

"Approximately one quarter of women diagnosed with Lynch syndrome-associated CRC (colorectal cancer) developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women."