Person:

Lee, I-Min

Background: Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions. Methods and Findings: We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40–69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking. Conclusions: These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.

Introduction: Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case–control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods: We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case–control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results: Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions: Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women.

OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.

Objective: Variation in the fat mass and obesity-associated (FTO) gene is associated with obesity. The extent to which separate and combined effects of physical activity and caloric intake modify this association remains unclear. Research Design and Methods: FTO polymorphism rs8050136 was measured, and physical activity, caloric intake, and anthropometrics were self-reported in 21,675 apparently healthy Caucasian women. Results: The effect of the risk allele (A) on BMI was larger among inactive or higher intake women, with additive effects of inactivity and high intake on the associated genetic risk. Specifically, each A allele was associated with mean BMI difference of +0.73 (SE 0.08) kg/m(^2) among inactive women ((\leq)median, 8.8 MET-hours/week), compared with +0.31 (0.06) kg/m(^2), P < 0.0001, among active women (>8.8 MET-hours/week). Similarly, each A allele was associated with mean BMI difference of +0.65 (0.07) among high intake women (>median, 1,679 kcals/day), compared with +0.38 (0.07) kg/m(^2), P = 0.005, among low intake women ((\leq)1,679 kcals/day). Among inactive/high intake women, each A allele was associated with mean BMI difference of +0.97 (0.11) kg/m(^2) vs. +0.22 (0.08) kg/m(^2) among inactive/low intake women, P < 0.0001. Among inactive/high intake women, each A allele carried increased risk of obesity (odds ratio 1.39, 95% CI 1.27–1.52) and diabetes (odds ratio 1.36, 95% CI 1.07–1.73). Conclusions: In this study, lifestyle factors modified the genetic risk of FTO on obesity phenotypes, particularly among women who were both inactive and had high intake. Healthier lifestyle patterns blunted but did not completely eliminate the associated genetic risk.

Objectives: To determine the impact of sitting and television viewing on life expectancy in the USA. Design: Prevalence-based cause-deleted life table analysis. Setting: Summary RRs of all-cause mortality associated with sitting and television viewing were obtained from a meta-analysis of available prospective cohort studies. Prevalences of sitting and television viewing were obtained from the US National Health and Nutrition Examination Survey. Primary outcome measure: Life expectancy at birth. Results: The estimated gains in life expectancy in the US population were 2.00 years for reducing excessive sitting to <3 h/day and a gain of 1.38 years from reducing excessive television viewing to <2 h/day. The lower and upper limits from a sensitivity analysis that involved simultaneously varying the estimates of RR (using the upper and lower bounds of the 95% CI) and the prevalence of television viewing (±20%) were 1.39 and 2.69 years for sitting and 0.48 and 2.51 years for television viewing, respectively. Conclusion: Reducing sedentary behaviours such as sitting and television viewing may have the potential to increase life expectancy in the USA.

Background:: The association between adiposity in early adulthood and subsequent development of specific malignancies is unclear. Further, the potential for mediation by adiposity in middle age has not been well examined. In a rare study, we investigated the association of body mass index (BMI) in early adulthood with mortality from several site-specific cancers. Design: In the Harvard Alumni Health Study cohort, 19 593 males had a physical examination at the university between 1914 and 1952 (mean age: 18.4 years) and returned a questionnaire in 1962 or 1966 (mean age = 45.1 years). BMI was computed using weight (kg)/(height^2) ((m^2)) at both time points. Vital status follow up continued for a maximum of 82 years. Results: Positive early adulthood cancer mortality gradients by BMI were found for all malignancies combined (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.05–1.17 for a one standard deviation increase in early adulthood BMI), and for lung (HR = 1.24; 95% CI = 1.10–1.40) and skin (HR = 1.29; 95% CI = 0.96–1.75) cancers. There were also apparent associations for cancers of the oesophagus and urogenital sites. Mediation by BMI in middle age was found to be minimal. Conclusion: Higher BMI in early adulthood appears to be a direct risk factor for selected malignancies several decades later.

Background: Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. Methods and Findings: We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21–90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1–3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6–2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3–4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5–24.9) was associated with a gain of 7.2 (95% CI: 6.5–7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. Conclusions: More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups.

Background: Physical activity and adiposity are important predictors of mortality, even in older individuals. However, it is unclear how much physical activity is needed to prevent weight gain in older persons. Purpose To examine the associations of different amounts of physical activity with weight gain prevention in older men. Methods: 5,973 healthy men (mean age, 65.0 y) from the Harvard Alumni Health Study were followed from 1988 to 1998. At baseline (1988), in 1993, and 1998, men reported their recreational physical activity and body weight. Physical activity was categorized as: <7.5 MET-hr/week (7.5 MET-hr/week corresponds to the minimum required by the 2008 US federal guidelines), 7.5 to <21 MET-hr/week (21 MET-hr/week corresponds to the 2002 Institute of Medicine [IOM] guideline), and ≥21 MET-hr/week. Meaningful weight gain was defined as an increase of ≥3% of body weight. Results: Overall, weight tended to be stable over any 5-year period; mean change, −0.08 (SD=4.44) kg. However, ~21% of men experienced meaningful weight gain over any 5-year period. In multivariate analyses, compared to men expending ≥21 MET-hr/week, those expending 7.5 to <21 MET-hr/week had an odds ratio (OR) of 1.35 (95% confidence interval: 1.03, 1.77) for meaningful weight gain, and men expending <7.5 MET-hr/week, an OR of 1.16 (1.01, 1.33) (p, trend = 0.09). Conclusions: Among older men, those with lesser levels of physical activity were more likely to gain weight than men satisfying the 2002 IOM guidelines of ≥21 MET-hr/week (~60 minutes per day of moderate-intensity physical activity).

Background: Despite recent advances in surveillance of physical activity, data on time trends of physical activity in low and middle-income countries are lacking. This study describes time trends in physical activity and television viewing between 2006 and 2012 among Brazilian adults. Methods: Data from 371,271 adult participants (18 + years) in the Surveillance System for Risk and Protective Factors for Chronic Illnesses using Telephone Survey (VIGITEL) were analysed. Time trends in leisure-time physical activity (≥ 5 days/wk; ≥ 30 min/day), transportation physical activity (using bicycle or walking for ≥ 30 minutes per day as a means of transportation to/from work) and proportion of participants spending more than three hours per day watching television were analysed. Annual changes according to sex, age and years of schooling were calculated. Results: There was an increase in leisure-time physical activity from 12.8% in 2006 to 14.9% in 2012 (annual increase of 1.9%; p < 0.001). This increase was more marked in younger participants and those with high-school education. Transportation physical activity decreased 12.9% per year (p < 0.001) from 2006 to 2008 and 5.8% per year from 2009 to 2012 (p < 0.001). The annual decline in television viewing time was 5% (p < 0.001) between 2006 and 2009 and 2% (p = 0.16) between 2010 and 2012. Conclusion: National survey data from Brazil indicate that leisure-time physical activity appears to be increasing, while television viewing time appears to be decreasing in recent years. However, transportation physical activity has been declining. These data are important for informing national public health policies.

Background: The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods: We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results: Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion: These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI.