Breast cancer detection in relation to oral contraception.

Analyses of tumor size and breast cancer stage were used to determine whether biased detection of breast cancer could have materially influenced estimates of risk associated with use of oral contraceptives. In a population-based case-control study conducted from 1980-1982, surveillance for breast cancer by breast exams, but not mammography, was found to be strongly linked to use of oral contraceptives. Tumors were slightly smaller and less likely to be late-stage (TNM stage III or IV) in patients who had used oral contraceptives. The net effect of any diagnostic bias on advancing the date of cancer diagnosis, whether from breast exams or other sources, was estimated to be less than 8 weeks. This corresponds to spuriously increasing the risk of early-occurring breast cancer in oral contraceptive users by at most 2.4% (relative risk = 1.024).     

Cancer Prevention in the Dental Practice: Oral Cancer Screening and Tobacco Cessation Advice

Objectives : In this paper we describe the proportion of US adults who report receiving oral cancer screening and tobacco cessation counseling and assistance from dentists and other health professionals. Methods : Data from the 1992 National Health Interview Survey (NHIS) Cancer Control Supplement, a nationally representative sample of 12,035 adults 18 years of age and older, are analyzed. Results : In 1992, less than 10 percent of adults reported oral cancer screening by a dentist or hygienist within the past three years. White adults (10.1%; 95% Cl=9.3,10.9) reported an oral cancer screening three times more frequently than black (3.2%; 95% Cl=1.9, 4.5) or Hispanic (3.4%; 95% Cl=2.1, 4.7) adults. About half of adult current smokers had seen a dentist within 12 months, and of those only 24.1 percent (95% Cl=21.7, 26.5) had been advised to quit smoking. Heavy smokers (two or more packs a day) were more likely to have been advised to quit than light (pack or less per day) or occasional smokers. A similar proportion (24.3%; 95% Cl=17.6, 31.0) of white adult men who reported using smokeless tobacco products had been told by a dentist to quit using tobacco. Conclusions : Results from this population-based survey indicate that cancer screening and tobacco cessation advice are underutilized in the dental practice. Increased patient awareness and implementation of screening and tobacco cessation interventions could improve oral cancer incidence and mortality and have a public health benefit for other tobacco-related morbidity and mortality as well.     

Hysterectomy, tubal sterilization, and the risk of breast cancer

Studies suggest that hysterectomy and tubal sterilization may alter the function of the remaining ovaries. Conceivably, this effect could alter breast cancer risk. To investigate whether these surgeries affect breast cancer risk, the authors analyzed data collected between December 1, 1980, and April 30, 1983, in a population-based, case-control study of women aged 20-54 years, the Cancer and Steroid Hormone Study. Compared with never-sterilized women, women with hysterectomy and no remaining ovaries had a decreased risk of breast cancer (relative risk (RR) = 0.7, 95% confidence interval (CI) = 0.6-0.8). Risk was lowest in women who had their surgery before age 40 years or 15 or more years in the past; surgery at an early age provided greater protection than surgery in the distant past. Hysterectomy with one or two remaining ovaries was also inversely associated with breast cancer risk (RR = 0.8, 95% CI = 0.7-0.9), but no relation was found with age at surgery or time since surgery. Women with tubal sterilization had a slightly increased risk of breast cancer, which was of borderline statistical significance (RR = 1.2, 95% CI = 1.0-1.3). However, no relation was found with age at surgery or time since surgery. The data suggest that hysterectomy with bilateral oophorectomy decreases the breast cancer risk in women aged less than 55 years, possibly by curtailing ovarian function at a critical period. However, neither hysterectomy without bilateral oophorectomy nor tubal sterilization appears to substantially alter breast cancer risk in women of this age.     

Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch

The function of the human cardiac voltage-gated sodium channel Na(V)1.5 (hH1) is regulated in part by binding of calcium to an EF hand in the C-terminal cytoplasmic domain. hH1 is also regulated via an extrinsic calcium-sensing pathway mediated by calmodulin (CaM) via binding to an IQ motif immediately adjacent to the EF-hand domain. The intrinsic EF-hand domain is shown here to interact with the IQ motif, which controls calcium affinity. Remarkably, mutation of the IQ residues has only a minor effect on CaM affinity but drastically reduces calcium affinity of the EF-hand domain, whereas the Brugada mutation A1924T significantly reduces CaM affinity but has no effect on calcium affinity of the EF-hand domain. Moreover, the differences in the biochemical effects of the mutations directly correlate with contrasting effects on channel electrophysiology. A comprehensive model is proposed in which the hH1 IQ motif serves as a molecular switch, coupling the intrinsic and extrinsic calcium sensors.