The KL-VS sequence variant of Klotho and cancer risk in BRCA1 and BRCA2 mutation carriers

Klotho (KL) is a putative tumor suppressor gene in breast and pancreatic cancers located at chromosome 13q12. A functional sequence variant of Klotho (KL-VS) was previously reported to modify breast cancer risk in Jewish BRCA1 mutation carriers. The effect of this variant on breast and ovarian cancer risks in non-Jewish BRCA1/BRCA2 mutation carriers has not been reported. The KL-VS variant was genotyped in women of European ancestry carrying a BRCA mutation: 5,741 BRCA1 mutation carriers (2,997 with breast cancer, 705 with ovarian cancer, and 2,039 cancer free women) and 3,339 BRCA2 mutation carriers (1,846 with breast cancer, 207 with ovarian cancer, and 1,286 cancer free women) from 16 centers. Genotyping was accomplished using TaqMan^® allelic discrimination or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed within a retrospective cohort approach, stratified by country of origin and Ashkenazi Jewish origin. The per-allele hazard ratio (HR) for breast cancer was 1.02 (95% CI 0.93–1.12, P = 0.66) for BRCA1 mutation carriers and 0.92 (95% CI 0.82–1.04, P = 0.17) for BRCA2 mutation carriers. Results remained unaltered when analysis excluded prevalent breast cancer cases. Similarly, the per-allele HR for ovarian cancer was 1.01 (95% CI 0.84–1.20, P = 0.95) for BRCA1 mutation carriers and 0.9 (95% CI 0.66–1.22, P = 0.45) for BRCA2 mutation carriers. The risk did not change when carriers of the 6174delT mutation were excluded. There was a lack of association of the KL-VS Klotho variant with either breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.     

Incomplete pregnancy is not associated with breast cancer risk: the California Teachers Study

BACKGROUND: Early studies of incomplete pregnancy and development of breast cancer suggested that induced abortion might increase risk. Several large prospective studies, which eliminate recall bias, did not detect associations, but this relationship continues to be debated. STUDY DESIGN: To further inform this important question, we examined invasive breast cancer as it relates to incomplete pregnancy, including total number of induced abortions, age at first induced abortion and total number of miscarriages among women participating in the ongoing California Teachers Study (CTS) cohort. Incomplete pregnancy was self-reported on the CTS baseline questionnaire in 1995-1996. Incident breast cancers were ascertained in 3324 women through 2004 via linkage with the California Cancer Registry. RESULTS: Using Cox multivariable regression, we found no statistically significant association between any measure of incomplete pregnancy and breast cancer risk among nulliparous or parous women. CONCLUSION: These results provide strong evidence that there is no relationship between incomplete pregnancy and breast cancer risk.     

Large ethnic variations in recommended physical activity according to activity domains in amsterdam, the netherlands

Purpose

The level of recommended physical activity (PA) is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of culturally-specific activity.

Methods

Participants were sampled from the population based SUNSET study and were from ethnic Dutch (n = 567), Hindustani-Surinamese (n = 370) and African-Surinamese (n = 689) descent. The validated SQUASH-questionnaire measured PA for the following domains: commuting, occupation, household, leisure time. Culturally-specific activities were added as extra question within the leisure time domain. The effect of each domain on ethnic differences in recommended PA prevalence was examined by odds-ratio (OR) analysis through recalculating recommended PA, while, in turn, excluding the contribution of each domain.

Results

In the ethnic Dutch population, more vigorous PA in commuting and leisure time was reported compared to the Surinamese groups. The Hindustani-Surinamese and African-Surinamese reported more walking as commuting activity, while the Dutch group reported cycling more frequently. Ethnic differences in recommended PA became smaller in both Surinamese groups compared with the Dutch after removing commuting activity, for example, in Hindustani-Surinamese men (OR = 0.92, 95%CI: 0.62-1.37 vs. OR = 1.33, 0.89-2.00) and women (OR = 1.61, 1.12-2.32 vs. OR = 2.03, 1.41-2.92). Removing occupational activity resulted in larger ethnic differences in both groups compared with the Dutch. Smaller effects were found for yoga and dancing, leisure time and household activities.

Conclusion

This study shows that differences in PA between ethnic minority groups and the general population vary according to the activity domain. The results indicate that including all relevant domains and activities is essential for assessment of ethnic differences in recommended PA.     

The development and validation of the daily electronic Endometriosis Pain and Bleeding Diary

Background  

The objective of this study was to develop and validate a daily electronic Endometriosis Pain and Bleeding Diary (EPBD) for assessing treatment-related changes in endometriosis symptoms from the patient's perspective in a clinical trial setting.     

A Study of Hostility,Career Choice and Job Satisfaction Among Surgeons

The present study has been carried out to study the hostility pattern of surgeons and compare it with other specialities. 100 teachers working in different specialities in Post Graduate Institute of Medical Sciences (PGIMS) Rohtak (Surgery and allied specialties 21, Medical and allied specialities 14, Non-clinical specialities 30) were given Hostility and Direction of Hostility Questionnaire (HDHQ) along with questions regarding their choice of career and Job satisfaction. Hostility pattern did not differ statistically among these groups. Surgeons showed strong aptitude for the field and were contended with their choice of speciality but their Job satisfaction was low. Possible explanations and implications of the study are discussed.Key Words: Hostility, Job satisfaction, Surgeons     

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

Background  

Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease.     

Knowledge, Attitudes, and Interest in Breast-Ovarian Cancer Gene Testing: A Survey of a Large African-American Kindred with a BRCA1 Mutation

BACKGROUND: This study assessed counseling and testing needs from the perspective of adult members of a large African-American kindred with a BRCA1 mutation. METHODS: Interviews were conducted with 95 male and female kindred members to elicit information on sociodemographics, attitudes toward health care providers, breast cancer screening behaviors, and religious/spiritual beliefs, as well as to evaluate psychological distress, beliefs, knowledge, and attitudes related to genetic testing. RESULTS: Knowledge about breast and ovarian cancer genetics was limited. Adherence to screening recommendations was low among females with no personal breast or ovarian cancer history. The majority (67%) wished to discuss risk factors with a health care provider. Most participants (82%) indicated that they would have a genetic test if it were available. Significant predictors of intent to undergo testing were having at least one first-degree relative with breast and/or ovarian cancer (OR = 5.1; 95% CI = 1.2-20.9) and perceived risk of being a gene carrier > or =50% (OR = 64.3; 95% CI = 5.1-803.9) or reporting that they did not know their risk of being a gene carrier (OR = 10.9; 95% CI = 2.1-57.7). Cited barriers to testing included cost and availability. CONCLUSION: There is a high interest level in genetic testing despite limited knowledge about cancer genetics among these high-risk African Americans. Our study provides information for designing a genetic education and counseling intervention for this and similar families.