25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women.

INTRODUCTION: Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms. STUDY DESIGN: Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial. MAIN OUTCOME MEASURES: 25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling. RESULTS: The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R=0.29, p<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile. CONCLUSIONS: Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.

Alcohol and folate intake and breast cancer risk in the WHI Observational Study.

BACKGROUND: Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship. OBJECTIVE: To examine the relationship among breast cancer, alcohol and folate in the Women's Health Initiative-Observational Study (WHI-OS). METHODS: 88,530 postmenopausal women 50-79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer. RESULTS: 1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001-1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96-1.32; >5-15 g/d HR = 1.14, 95%CI 0.99-1.31; and >15 g/d HR = 1.13 95%CI 0.96-1.32). We found no significant interaction between alcohol and folate in our adjusted model. CONCLUSIONS: We found no evidence for folate attenuating alcohol's effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.

Calcium plus vitamin D supplementation and the risk of breast cancer.

BACKGROUND: Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. METHODS: Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. RESULTS: Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20). CONCLUSIONS: Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.

CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults. OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke. DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study. MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study. RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease. CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

Whole genome amplification of buccal cell DNA: genotyping concordance before and after multiple displacement amplification.

While buccal cells provide an easily accessible source of genomic DNA, the amount extracted may be insufficient for many studies. Whole genome amplification (WGA) using multiple displacement amplification (MDA) may optimize buccal cell genomic DNA yield. We compared the usefulness, in epidemiological surveys, of DNA derived from buccal cells collected by alcohol mouthwash and amplified by WGA protocol and standard protocols. Buccal cell collection kits were mailed to 300 randomly selected members of a large cohort study, and 189 subjects returned buccal cell samples. We determined: (i) which QIAamp DNA Blood Mini Kit extraction protocol (tissue or blood) produced more DNA; and (ii) whether it is feasible to use MDA to prepare DNA for single nucleotide polymorphism (SNP) genotyping of markers such as the methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR) genes. The two DNA extraction protocols were tested on 20 different patient samples each. The tissue protocol yielded more DNA than the blood protocol (15.4+/-8.6 vs. 7.6+/-7.1 microg, p<0.0001). The 20 DNA samples extracted using the tissue protocol were then subjected to pre- and post-MDA genotyping using amplicons for the MTHFR SNP at C677T and the intron 8 VDR SNP. No genotyping discrepancies were detected in pair-wise comparisons of pre- and post-MDA. Genotyping DNA from MDA-based WGA is indistinguishable from routine polymerase chain reaction and offers a stable DNA source for genomic research and clinical diagnosis.

Smoking cessation and lung cancer mortality in a cohort of middle-aged Canadian women.

PURPOSE: To determine the impact of smoking cessation on lung cancer mortality among women. METHODS: Survival analysis is used to assess the effect of smoking cessation on lung cancer death in the dietary cohort of 49,165 women aged 40 to 59 years enrolled in the Canadian National Breast Screening Study. RESULTS: During an average of 10.3 years of follow-up, 106 women died of lung cancer. The risk of lung cancer mortality among women who quit before age 50 (HR=0.26; 95% CI, 0.13-0.55 among women who quit at ages 40-49) or quit in the previous 10 years (HR=0.39; 95% CI, 0.22-0.69) is substantially lower than the risk among current smokers. Women who quit after age 40 or have quit for less than 20 years are at substantially higher risk of lung cancer mortality compared with never smokers. Both duration of smoking cessation and age at quitting have independent effects on lung cancer mortality, after controlling for number of cigarettes smoked per day and number of years smoked, as well as other potential confounding variables. CONCLUSION: These findings suggest that programs and policies to promote early cessation of smoking and prevention of relapse should be a public health priority.

Changes in survival patterns in urban Chinese patients with liver cancer.

AIM: To examine the survival patterns and determinants of primary liver cancer in a geographically defined Chinese population. METHODS: Primary liver cancer cases (n=13 685) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-adjusted and age-specific incidence rates were examined in both males and females. Proportional hazards (Cox) regression was utilized to explore the effects of time of diagnosis, sex, age, occupation, residence, and hospital of diagnosis on survival. RESULTS: Crude and age-adjusted incidence rates in the study period were: 27.4/100 000 and 26.3/100 000 in males; and 11.5/100 000 and 10.4/100 000 in females, respectively. Cox regression analyses indicated that there was a significant improvement in survival rates over time. Industrial workers and older people had relatively poor survival rates. The hospital in which the liver cancer was diagnosed was a statistically significant predictor of survival; patients diagnosed in city hospitals were more likely to have better survival than those diagnosed in community/district hospitals. CONCLUSION: Patients diagnosed in recent years appeared to have a better outcome than those diagnosed in early times. There were also significant survival disparities with respect to occupation and hospital of diagnosis, which suggest that socioeconomic status may play an important role in determining prognosis.

The development of a questionnaire to assess past year physical activity in a multi-ethnic/racial urban population.

OBJECTIVES: Describe the development of a questionnaire to assess past year physical activity, including activities of daily living, in a multi-ethnic/racial cohort. Describe energy expenditure (EE) patterns in the sample used for questionnaire development. METHODS: 24-hour activity recalls were collected from a convenience sample (N = 367) at four New York City health agencies (October 1999-February 2000). EE was determined at the population, subgroup, and individual level. EE distributions were compared. RESULTS: Activities identified were similar to those on established questionnaires. Subgroup and individual EE differences were noted. Median EE at the Chinese and Puerto Rican sites were lower than those at the Caribbean or Dominican sites. No clear age pattern was apparent. Overall, a greater percentage of daily EE was spent in low intensity activities. The resultant 30-minute interviewer-administered questionnaire ascertains patterns (frequency and duration) of domain-specific (recreational, household, occupational, and transportation) activity. This information combined with published intensity levels provides summary EE measures. CONCLUSION: Variation in EE levels requires information on activity type and amount. Summary activity measures can be used to rank individuals analogous to nutrient food frequency measures.

Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia.

In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR)=4.5; 95% confidence interval (CI), 1.6-12.4] than European (E) variants (OR=2.5; 95% CI, 1.3-4.9), relative to the risk of persistence for non-oncogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age- and race-adjusted OR=172.2; 95% CI, 47.1-630.1) and incident [relative risk (RR)=22.5; 95% CI, 6.0-83.9] high-grade lesions than E variants (prevalent lesions OR=46.3; 95% CI, 15.5-138.0 and incident lesons RR=6.1; 95% CI, 1.3-27.4), relative to the risk for HPV-negative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.