Alcohol intake, specific alcoholic beverages, and risk of hip fractures in postmenopausal women and men age 50 and older.

BACKGROUND: Although a number of studies have examined the association between alcohol intake and hip fractures, few have considered specific alcoholic beverages separately. OBJECTIVES: We prospectively assessed total alcohol and specific alcoholic beverage consumption and risk of hip fractures in US men and women. METHODS: Health, lifestyle information, and hip fractures were self-reported on biennial questionnaires between 1980 and 2014 in 75,180 postmenopausal women from the Nurses' Health Study, and between 1986 and 2014 in 38,398 men aged ≥50 y from the Health Professionals Follow-Up Study. Diet was assessed approximately every 4 y with a semiquantitative FFQ. RRs were computed for hip fracture using Cox proportional hazards models, adjusting for potential confounders. RESULTS: We ascertained 2360 incident low trauma hip fractures in women and 709 in men. Among women, RRs for low trauma hip fractures compared with nondrinkers were 0.89 (95% CI: 0.80, 0.99) for an average daily consumption of <5.0 g, 0.81 (95% CI: 0.70, 0.94) for 5.0 to <10.0 g, 0.83 (95% CI: 0.71, 0.96) for 10.0 to <20.0 g, and 0.93 (95% CI: 0.78, 1.10) for ≥20.0 g. Among men, risk declined linearly with higher alcohol consumption (P-trend = 0.002). Multivariable RR compared with nondrinkers was 0.77 (95% CI: 0.59, 1.01), 0.69 (0.49, 0.96), and 0.67 (0.48, 0.95) for an average intake of 10 g/d to <20 g/d, 20 g/d to <30 g/d, and 30.0 g/d or more, respectively. In women, the alcoholic beverage most significantly associated with hip fracture risk was red wine (RR per serving = 0.59; 95% CI: 0.45, 0.79). In men, there was no clear association with specific alcoholic beverages. CONCLUSION: In these 2 US cohorts, low to moderate alcohol consumption, when compared with no consumption, was associated with a lower risk of hip fractures, particularly with red wine consumption among women.

Association of High Intakes of Vitamins B6 and B12 From Food and Supplements With Risk of Hip Fracture Among Postmenopausal Women in the Nurses' Health Study.

Importance: Vitamin supplementation far exceeding recommended doses is popular in segments of the population. However, adverse effects can occur. In a previous secondary analysis of combined data from 2 double-blind randomized clinical trials (RCTs), an unexpected increased risk of hip fracture was found among those treated with high doses of vitamin B6 in combination with vitamin B12. Objectives: To study if high intakes of vitamins B6 and B12 from food and supplements were associated with a risk of hip fracture in the Nurses' Health Study and to investigate whether combined high intakes of both vitamins conferred a particularly increased fracture risk. Design, Setting, and Participants: In this prospective cohort study, 75 864 postmenopausal women in the United States were followed up from June 1984 through May 2014. The dates of analysis were July 2016 to June 2018. Information on hip fracture and a wide range of potential confounders was collected at baseline and with biennial follow-up questionnaires. Extensive dietary information was collected approximately every 4 years with a semiquantitative food frequency questionnaire. Relative risks (RRs) were calculated by Cox proportional hazards regression, with cumulative average intakes of vitamins B6 and B12 as main exposures, adjusting for potential confounders. Main Outcome and Measure: Hip fracture. Results: During follow-up, 2304 of 75 864 women had a hip fracture. Among the women with hip fractures, the median (range) age at hip fracture was 75.8 (46.7-93.0) years and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24.3 (4.6). Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) µg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 µg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 µg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 µg/d). Conclusions and Relevance: In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.

Milk drinking and risk of hip fracture: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).

Milk provides energy and nutrients considered protective for bone. Meta-analyses of cohort studies have found no clear association between milk drinking and risk of hip fracture, and results of recent studies are contradictory. We studied the association between milk drinking and hip fracture in Norway, which has a population characterised by high fracture incidence and a high Ca intake. Baseline data from two population-based cohorts were used: the third wave of the Norwegian Counties Study (1985-1988) and the Five Counties Study (2000-2002). Diet and lifestyle variables were self-reported through questionnaires. Height and weight were measured. Hip fractures were identified by linkage to hospital data with follow-up through 2013. Of the 35 114 participants in the Norwegian Counties Study, 1865 suffered a hip fracture during 613 018 person-years of follow-up. In multivariable Cox regression, hazard ratios (HR) per daily glass of milk were 0·97 (95 % CI 0·92, 1·03) in men and 1·02 (95 % CI 0·96, 1·07) in women. Of 23 259 participants in the Five Counties Study, 1466 suffered a hip fracture during 252 996 person-years of follow-up. HR for hip fractures per daily glass of milk in multivariable Cox regression was 0·99 (95 % CI 0·92, 1·07) in men and 1·02 (95 % CI 0·97, 1·08) in women. In conclusion, there was no overall association between milk intake and risk of hip fracture in Norwegian men and women.

Medicare Utilization and Spending Among Nurses Compared with the General United States Population.

Background: To better understand health habits in older nurses versus the general population, we sought to determine whether the demographics, health care utilization, and Medicare spending by the Nurses' Health Study (NHS) participants enrolled in Medicare and a matched sample of Medicare beneficiaries meaningfully differed. Materials and Methods: Analytic cohorts included a random 20% sample of Medicare beneficiaries continuously enrolled in fee for service (FFS) Medicare that were propensity matched to the NHS participants continuously enrolled in FFS Medicare in a single year (2012). Matching was based upon preselected demographic factors and health status, using a nearest-neighbor matching algorithm to obtain a 1:1 match without replacement. Healthcare utilization and spending were compared between the two groups; we also stratified findings by number of chronic comorbidities. Results: Similar rates of utilization of primary care and most outpatient services. However, NHS participants had slightly higher rates of cancer screening, specialist care, and inpatient surgery were observed. When stratified by comorbidity status, the largest differences in utilization and spending were found in women with no comorbidity. Conclusions: The modest differences in observed healthcare utilization and spending suggest that older healthcare professionals may access care in fairly similar ways to the general population, and that health status may be a more important determinant of utilization and spending than health profession in older age groups.

Association between Diet Quality Scores and Risk of Hip Fracture in Postmenopausal Women and Men Aged 50 Years and Older.

BACKGROUND: Although a number of studies showed a lower risk of hip fractures with high-quality diets, few of them were conducted in the United States. OBJECTIVE: This prospective analysis examined the association between several diet quality indexes and risk of hip fractures in US men and women. DESIGN: This is a prospective cohort study. PARTICIPANTS/SETTING: The participants were 74,446 postmenopausal women from the Nurses' Health Study and 36,602 men aged 50 years and older from the Health Professionals Follow-Up Study in the United States. MAIN OUTCOME MEASURE: Hip fractures were self-reported on biennial questionnaires between 1980-2012 in women, and between 1986-2012 in men. STATISTICAL ANALYSIS: Diet was assessed every 4 years with a validated food frequency questionnaire. Relative risks were computed for hip fracture by quintiles of the Alternate Mediterranean Diet score (aMed), the Alternate Healthy Eating Index-2010 (AHEI-2010), and the Dietary Approaches to Stop Hypertension score using Cox proportional hazards models, adjusting for potential confounders. RESULTS: Two thousand one hundred forty-three incident hip fractures in women and 603 in men were reported during follow-up. A significant inverse trend was observed with the cumulative AHEI-2010 score in women (relative risk comparing extreme quintiles 0.87, 95% CI 0.75 to 1.00; P for trend=0.02). There was also a suggestion of an inverse association with the Dietary Approaches to Stop Hypertension score (P for trend=0.03). In addition, significant inverse trends were observed between all three diet quality scores and hip fractures in women younger than age 75 years but not older women. There was no clear association between diet quality indexes and hip fracture in men. CONCLUSIONS: Higher AHEI-2010 scores were associated with a lower risk of hip fractures in US women. The inverse associations with diet quality may be more apparent among those younger than age 75 years.

Leveraging Linkage of Cohort Studies With Administrative Claims Data to Identify Individuals With Cancer.

BACKGROUND: In an effort to overcome quality and cost constraints inherent in population-based research, diverse data sources are increasingly being combined. In this paper, we describe the performance of a Medicare claims-based incident cancer identification algorithm in comparison with observational cohort data from the Nurses' Health Study (NHS). METHODS: NHS-Medicare linked participants' claims data were analyzed using 4 versions of a cancer identification algorithm across 3 cancer sites (breast, colorectal, and lung). The algorithms evaluated included an update of the original Setoguchi algorithm, and 3 other versions that differed in the data used for prevalent cancer exclusions. RESULTS: The algorithm that yielded the highest positive predictive value (PPV) (0.52-0.82) and κ statistic (0.62-0.87) in identifying incident cancer cases utilized both Medicare claims and observational cohort data (NHS) to remove prevalent cases. The algorithm that only used NHS data to inform the removal of prevalent cancer cases performed nearly equivalently in statistical performance (PPV, 0.50-0.79; κ, 0.61-0.85), whereas the version that used only claims to inform the removal of prevalent cancer cases performed substantially worse (PPV, 0.42-0.60; κ, 0.54-0.70), in comparison with the dual data source-informed algorithm. CONCLUSIONS: Our findings suggest claims-based algorithms identify incident cancer with variable reliability when measured against an observational cohort study reference standard. Self-reported baseline information available in cohort studies is more effective in removing prevalent cancer cases than are claims data algorithms. Use of claims-based algorithms should be tailored to the research question at hand and the nature of available observational cohort data.

A Preliminary Evaluation of the Ability of Keratotic Tissue to Act as a Prognostic Indicator of Hip Fracture Risk.

Studies have shown that Raman spectroscopic analysis of fingernail clippings can help differentiate between post-menopausal women who have and who have not suffered a fracture. However, all studies to date have been retrospective in nature, comparing the proteins in nails sourced from women, post-fracture. The objective of this study was to investigate the potential of a prospective test for hip fracture based on spectroscopic analysis of nail tissue. Archived toenail samples from post-menopausal women aged 50 to 63 years in the Nurses' Health Study were obtained and analysed by Raman spectroscopy. Nails were matched case-controls sourced from 161 women; 82 who underwent a hip fracture up to 20 years after nail collection and 81 age-matched controls. A number of clinical risk factors (CRFs) from the Fracture Risk Assessment (FRAX) tool had been assessed at toenail collection. Using 80% of the spectra, models were developed for increasing time periods between nail collection and fracture. Scores were calculated from these models for the other 20% of the sample and the ability of the score to predict hip fracture was tested in model with and without the CRFs by comparing the odds ratios (ORs) per 1 SD increase in standardised predictive values. The Raman score successfully distinguished between hip fracture cases and controls. With only the score as a predictor, a statistically significant OR of 2.2 (95% confidence interval [CI]: 1.5-3.1) was found for hip fracture for up to 20 years after collection. The OR increased to 3.8 (2.6-5.4) when the CRFs were added to the model. For fractures limited to 13 years after collection, the OR was 6.3 (3.0-13.1) for the score alone. The test based on Raman spectroscopy has potential for identifying individuals who may suffer hip fractures several years in advance. Higher powered studies are required to evaluate the predictive capability of this test.

Burden of hip fracture using disability-adjusted life-years: a pooled analysis of prospective cohorts in the CHANCES consortium.

BACKGROUND: No studies have estimated disability-adjusted life-years (DALYs) lost due to hip fractures using real-life follow-up cohort data. We aimed to quantify the burden of disease due to incident hip fracture using DALYs in prospective cohorts in the CHANCES consortium, and to calculate population attributable fractions based on DALYs for specific risk factors. METHODS: We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs. We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates. We calculated population attributable fractions for smoking, body-mass index (BMI), physical activity, alcohol intake, type 2 diabetes and parity, use of hormone replacement therapy, and oral contraceptives in women. We calculated summary risk estimates across cohorts with pooled analysis and random-effects meta-analysis methods. FINDINGS: 223 880 men and women were followed up for a mean of 13 years (SD 6). 7724 (3·5%) participants developed an incident hip fracture, of whom 413 (5·3%) died as a result. 5964 DALYs (27 per 1000 individuals) were lost due to hip fractures, 1230 (20·6%) of which were in the group aged 75-79 years. 4150 (69·6%) DALYs were attributed to disability. Current smoking was the risk factor responsible for the greatest hip fracture burden (7·5%, 95% CI 5·2-9·7) followed by physical inactivity (5·5%, 2·1-8·5), history of diabetes (2·8%, 2·1-4·0), and low to average BMI (2·0%, 1·4-2·7), whereas low alcohol consumption (0·01-2·5 g per day) and high BMI had a protective effect. INTERPRETATION: Hip fracture can lead to a substantial loss of healthy life-years in elderly people. National public health policies should be strengthened to reduce hip fracture incidence and mortality. Primary prevention measures should be strengthened to prevent falls, and reduce smoking and a sedentary lifestyle. FUNDING: European Community's Seventh Framework Programme.

Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.

Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status. Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident. Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.

Associations among rotating night shift work, sleep and skin cancer in Nurses' Health Study II participants.

BACKGROUND: Night shift work and sleep duration have been associated with breast and other cancers. Results from the few prior studies of night shift work and skin cancer risk have been mixed and not fully accounted for other potentially important health-related variables (eg, sleep characteristics). This study evaluated the relationship between rotating night shift work and skin cancer risk and included additional skin cancer risk factors and sleep-related variables. METHODS: The current study used data from 74 323 Nurses' Health Study (NHS) II participants. Cox proportional hazards models were used to estimate multivariable-adjusted HRs and 95% CIs for skin cancers across categories of shift work and sleep duration. RESULTS: Over 10 years of follow-up, 4308 basal cell carcinoma (BCC), 334 squamous cell carcinoma (SCC) and 212 melanoma cases were identified. Longer duration of rotating night shifts was associated with a linear decline in risk of BCC (HR=0.93, 95% CI 0.90 to 0.97 per 5-year increase). Shift work was not significantly associated with either melanoma (HR=1.02, 95% CI 0.86 to 1.21) or SCC (HR=0.92, 95% CI 0.80 to 1.06). A short sleep duration (≤6 hours per day) was associated with lower risks of melanoma (HR=0.68, 95% CI 0.46 to 0.98) and BCC (HR=0.93, 95% CI 0.86 to 1.00) compared with the most common report of 7 hours. SCC was not associated with duration of sleep (HR=0.94, 95% CI 0.83 to 1.06). CONCLUSIONS: Longer duration of rotating night shift work and shorter sleep duration were associated with lower risk of some skin cancers. Further research is needed to confirm and identify the mechanisms underlying these associations.

Gout and Risk of Fracture in Women: A Prospective Cohort Study.

OBJECTIVE: Uric acid may be linked to bone health through its antioxidant or prooxidant effects, thereby affecting bone resorption and formation, or through its dual inhibition of vitamin D activation and parathyroid hormone production. Results of prior studies on the relationship between uric acid and bone mineral density have been conflicting. This prospective study was undertaken to examine the relationship between gout, a disease characterized by hyperuricemia and inflammation, and risk of hip or wrist fracture in women. METHODS: We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses' Health Study (n = 103,799 at baseline, with 14 years of follow-up for the wrist fracture analysis and 22 years of follow-up for the hip fracture analysis). Gout history and incident cases of wrist and hip fracture were assessed by biennial questionnaire. Cox proportional hazards models were used to simultaneously adjust for potential confounders. RESULTS: In this cohort, there were 3,769 incident wrist fractures (1990-2004) and 2,147 incident hip fractures (1990-2012), with 107 wrist fractures and 117 hip fractures occurring in participants with gout. In those women with a history of gout compared with women without gout, the multivariable-adjusted relative risk of wrist fracture was 1.12 (95% confidence interval [95% CI] 0.92-1.36) and the multivariable-adjusted relative risk of hip fracture was 1.38 (95% CI 1.14-1.68). CONCLUSION: In women, a history of gout is associated with a modestly increased risk of hip fracture, but not significantly associated with a risk of wrist fracture.

Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project.

The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person-years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort-specific, food-frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta-analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (pfor heterogeneity = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. © 2016 American Society for Bone and Mineral Research.

Nephrolithiasis and Risk of Incident Bone Fracture.

PURPOSE: Higher urine calcium is a common feature of calcium nephrolithiasis and may be associated with lower bone mineral density in individuals with kidney stones. However previous population based studies of kidney stones and the risk of bone fracture demonstrate conflicting results. We examined independent associations between a history of kidney stones and incident fracture. MATERIALS AND METHODS: We performed prospective studies using data from the Nurses' Health Study of 107,001 women with 32 years of followup and the Health Professionals Follow-up Study of 50,982 men with 26 years of followup. We excluded premenopausal women, men younger than 45 years and individuals who reported osteoporosis at baseline. Study outcomes were incident wrist (distal radius) or incident hip (proximal femur) fracture due to low or moderate trauma. Cox proportional hazards regression was used to adjust for multiple factors, including age, race, body mass index, thiazide use, supplemental calcium and dietary intakes. RESULTS: There were 4,940 wrist and 2,391 hip fractures in women, and 862 wrist and 747 hip fractures in men. All fractures were incident. The multivariable adjusted relative risk of incident wrist fracture in participants with a history of kidney stones compared to participants without kidney stones was 1.18 (95% CI 1.04-1.34) in women and 1.21 (95% CI 1.00-1.47) in men. The pooled multivariable adjusted relative risk of wrist fracture was 1.20 (95% CI 1.08-1.33). The multivariable adjusted relative risk of incident hip fracture in participants with kidney stones was 0.96 (95% CI 0.80-1.14) in women and 0.92 (95% CI 0.74-1.14) in men. The pooled multivariable adjusted relative risk of hip fracture was 0.94 (95% CI 0.82-1.08). CONCLUSIONS: Nephrolithiasis is associated with a significantly higher risk of incident wrist but not hip fracture in women and men.

Neighborhood Self-Selection: The Role of Pre-Move Health Factors on the Built and Socioeconomic Environment.

Residential self-selection bias is a concern in studies of neighborhoods and health. This bias results from health behaviors predicting neighborhood choice. To quantify this bias, we examined associations between pre-move health factors (body mass index, walking, and total physical activity) and post-move neighborhood factors (County Sprawl Index, Census tract socioeconomic status (SES)) in the Nurses' Health Study (n = 14,159 moves from 1986-2008). Individuals in the highest quartile of pre-move BMI (BMI > 28.4) compared to the lowest quartile (BMI < 22.5) moved to counties that averaged 2.57 points lower on the sprawl index (95% confidence interval -3.55, -1.59) indicating that individuals moved to less dense counties; however, no associations were observed for pre-move walking nor total physical activity. Individuals with higher pre-move BMI tended to move to Census tracts with lower median income and home values and higher levels of poverty. Analyses examining the change in neighborhood environments after a move demonstrated that healthy pre-move behaviors were associated with moves to worse socioeconomic environments. This type of self-selection would bias results downward, underestimating the true relationship between SES and physical activity. Generally, the magnitudes of associations between pre-move health factors and neighborhood measures were small and indicated that residential self-selection was not a major source of bias in analyses in this population.

Citrus Consumption and Risk of Cutaneous Malignant Melanoma.

PURPOSE: Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption. METHODS: A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records. RESULTS: Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001). CONCLUSION: Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications.

Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin.

Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and 63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11) for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes.

Smoking and mortality--beyond established causes.

BACKGROUND: Mortality among current smokers is 2 to 3 times as high as that among persons who never smoked. Most of this excess mortality is believed to be explained by 21 common diseases that have been formally established as caused by cigarette smoking and are included in official estimates of smoking-attributable mortality in the United States. However, if smoking causes additional diseases, these official estimates may significantly underestimate the number of deaths attributable to smoking. METHODS: We pooled data from five contemporary U.S. cohort studies including 421,378 men and 532,651 women 55 years of age or older. Participants were followed from 2000 through 2011, and relative risks and 95% confidence intervals were estimated with the use of Cox proportional-hazards models adjusted for age, race, educational level, daily alcohol consumption, and cohort. RESULTS: During the follow-up period, there were 181,377 deaths, including 16,475 among current smokers. Overall, approximately 17% of the excess mortality among current smokers was due to associations with causes that are not currently established as attributable to smoking. These included associations between current smoking and deaths from renal failure (relative risk, 2.0; 95% confidence interval [CI], 1.7 to 2.3), intestinal ischemia (relative risk, 6.0; 95% CI, 4.5 to 8.1), hypertensive heart disease (relative risk, 2.4; 95% CI, 1.9 to 3.0), infections (relative risk, 2.3; 95% CI, 2.0 to 2.7), various respiratory diseases (relative risk, 2.0; 95% CI, 1.6 to 2.4), breast cancer (relative risk, 1.3; 95% CI, 1.2 to 1.5), and prostate cancer (relative risk, 1.4; 95% CI, 1.2 to 1.7). Among former smokers, the relative risk for each of these outcomes declined as the number of years since quitting increased. CONCLUSIONS: A substantial portion of the excess mortality among current smokers between 2000 and 2011 was due to associations with diseases that have not been formally established as caused by smoking. These associations should be investigated further and, when appropriate, taken into account when the mortality burden of smoking is investigated. (Funded by the American Cancer Society.).

What proportion of cancer deaths in the contemporary United States is attributable to cigarette smoking?

PURPOSE: The proportion of cancer deaths in the contemporary United States caused by cigarette smoking (the population attributable fraction [PAF]) is not well documented. METHODS: The PAF of all cancer deaths due to active cigarette smoking among adults 35 years and older in the United States in 2010 was calculated using age- and sex-specific smoking prevalence from the National Health Interview Survey (NHIS) and age- and sex-specific relative risks from the Cancer Prevention Study-II (for ages 35-54 years) and from the Pooled Contemporary Cohort data set (for ages 55 years and older). RESULTS: The PAF for active cigarette smoking was 28.7% when estimated conservatively, including only deaths from the 12 cancers currently formally established as caused by smoking by the US Surgeon General. The PAF was 31.7% when estimated more comprehensively, including excess deaths from all cancers. These estimates do not include additional potential cancer deaths from environmental tobacco smoke or other type of tobacco use such as cigars, pipes, or smokeless tobacco. CONCLUSIONS: Cigarette smoking causes a large proportion of cancer deaths in the contemporary United States. Reducing smoking prevalence as rapidly as possible should be a top priority for the US public health efforts to prevent cancer deaths.

Soda consumption and risk of hip fractures in postmenopausal women in the Nurses' Health Study.

BACKGROUND: The frequency of soda consumption remains high in the United States. Soda consumption has been associated with poor bone health in children, but few studies have examined this relation in adults, and to our knowledge, no study has examined the relation of soda consumption with risk of hip fractures. OBJECTIVE: We examined the association of soda, including specific types of soda, and risk of hip fracture in postmenopausal women. DESIGN: An analysis was conducted in postmenopausal women from the Nurses' Health Study cohort (n = 73,572). Diet was assessed at baseline by using a semiquantitative food-frequency questionnaire and updated approximately every 4 y. In ≤30 y of follow-up, we identified 1873 incident hip fractures. We computed RRs for hip fractures by the amount of soda consumption by using Cox proportional hazards models with adjustment for potential confounders. RESULTS: In multivariable models, each additional serving of total soda per day was associated with a significant 14% increased risk of hip fracture (RR: 1.14; 95% CI: 1.06, 1.23). The attributable risk in our cohort for total soda consumption was 12.5%. Risk was significantly elevated in consumers of both regular soda (RR: 1.19; 95% CI: 1.02, 1.38) and diet soda (RR: 1.12; 95% CI: 1.03, 1.21) and also did not significantly differ between colas and noncolas or sodas with or without caffeine. The association between soda and hip fractures did not differ by body mass index or diagnosis of diabetes. CONCLUSION: Increased soda consumption of all types may be associated with increased risk of hip fracture in postmenopausal women; however, a clear mechanism was not apparent on the basis of these observational data.