Pre-diagnosis recreational physical activity and lung cancer survival within the California teachers study

PurposeAlthough physical activity (PA) levels have been linked to decreased lung cancer mortality, the magnitude of associations and delineation of biological and behavioral risk factors is often inconsistent. Our study aims to address this gap by elucidating the associations of lung cancer mortality with time-varying and exertion-varying pre-diagnosis PA levels.MethodsWe examined the associations between PA and lung cancer mortality among 1,768 women enrolled in the California Teachers Study cohort and diagnosed with lung cancer between 1995–2019. Pre-diagnosis lifetime and recent PA were assessed. Multivariable Cox regressions provided hazard ratio (HR) and 95% confidence interval (CI) estimates.ResultsSimilar risks of lung cancer mortality were observed across all PA variables. Ever and/or former smokers who engaged in higher levels of moderate, lifetime PA had a lower risk of lung cancer mortality. Ever and/or current smokers who engaged in intermediate to high levels of strenuous, lifetime PA had increased risk of lung cancer mortality, while never smokers saw a protective effect on lung cancer mortality.ConclusionThe results of this study suggest that smoking significantly modifies the association between PA and lung cancer mortality. Although the mechanisms underlying these findings remain unclear, we hypothesize that excessive strenuous PA among ever and/or current smokers exacerbates the inflammatory damage already induced by smoke exposure, compromising immune cell recovery and leading to reduced lung cancer survival in this group.

Purpose: Most studies have shown a protective or null effect of postmenopausal hormone therapy (HT) on lung cancer risk, whereas the recent post-hoc analysis of the Women's Health Initiative (WHI) showed that estrogen+progestin (E+P) decreased lung cancer survival. Given the substantial clinical implications, it is vital that the risk and survival associations be validated. Methods: We examined the associations between HT use and lung cancer risk and survival among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, 727 women (184 never smokers) were diagnosed with lung cancer; 441 of these died as of December 31, 2007. Age-stratified, multivariable Cox proportional hazards regression was used to calculate hazard ratios (HR). Results: After adjusting for potential confounders, various measures of HT use were not associated with lung cancer risk. However, any HT use (vs. no use) was associated with a statistically significant increase in lung-cancer-specific survival [HR, 0.70; 95% confidence interval (CI), 0.56-0.87]. Among women who only used E, statistically significant increases in lung cancer survival were seen for recent use (HR, 0.59; 95% CI, 0.43-0.80), but not former use; use of only E+P was not associated with survival. Shorter duration of recent E-only use was associated with improved survival (0-5 years of use: HR, 0.29, 95% CI, 0.12-0.68; 5-15 years of use: HR, 0.60, 95% CI, 0.35-1.05; >15 years of use: HR, 0.58, 95% CI, 0.39-0.88) (trend P = 0.005). Similarly, women who reported recently using E-only for 0-5 years had a median survival time of 42.1 months versus women who reported 5-15 years of use (31 months), >15 years of use (19.1 months), or no HT use (15.6 months) (log-rank P = 0.009). Among former users of HT, a statistically significant 63% (95% CI, 0.16-0.87) decrease in lung-cancer-specific death was observed for E-only use <5 years prior to baseline, but not for E-only use >5 years prior to baseline or E+P-only use. Conclusions: Contrary to the recent finding that lung cancer survival is poorer among women in WHI taking E+P, our results suggest no effect of E+P. By contrast, postmenopausal E-only use, specifically recent use, is associated with increased lung cancer survival.

Previous results from research on menopausal hormone therapy (MHT) and lung cancer survival have been mixed and most have not studied women who used estrogen therapy (ET) exclusively. We examined the associations between MHT use reported at baseline and lung cancer-specific mortality in the prospective California Teachers Study cohort. Among 727 postmenopausal women diagnosed with lung cancer from 1995 through 2007, 441 women died before January 1, 2008. Hazard Ratios (HR) and 95% Confidence Intervals (CI) for lung-cancer-specific mortality were obtained by fitting multivariable Cox proportional hazards regression models using age in days as the timescale. Among women who used ET exclusively, decreases in lung cancer mortality were observed (HR, 0.69; 95% CI, 0.52–0.93). No association was observed for estrogen plus progestin therapy use. Among former users, shorter duration (<5 years) of exclusive ET use was associated with a decreased risk of lung cancer mortality (HR, 0.56; 95% CI, 0.35–0.89), whereas among recent users, longer duration (>15 years) was associated with a decreased risk (HR, 0.60; 95% CI, 0.38–0.95). Smoking status modified the associations with deceases in lung cancer mortality observed only among current smokers. Exclusive ET use was associated with decreased lung cancer mortality.

Incidence of lung cancer is decreasing among men and increasing among women in developed countries and also in Korea. However, mortality of lung cancer is still the highest among male cancers. Smoking is one of the group 1 carcinogens for lung cancer development, but its prognostic effect on lung cancer survival is not well established. Beta-carotene supplement increased the risk of lung cancer among smokers but the role of multivitamin supplement on the risk and survival of lung cancer is unclear either. We aimed to evaluate the association between smoking and multivitamin use on lung cancer survival by sex. We interviewed 910 pathologically confirmed lung cancer patients who were diagnosed between 2010 and 2012 in Samsung Medical Center. Questionnaire included current smoking status, age at first smoking, daily smoking amount, alcohol intake, past medical history, and multivitamin use. Pathological type, stage, and treatment information was collected from the electronic medical records. We followed the patients until December 31, 2012. Hazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox's proportional hazard model (SAS9.4). We found significant difference in age at diagnosis, pathological type and stage between male and female patients; Female patients were younger, smoked less, used more multivitamin, and had more adenocarcinoma and earlier stage cancer than male patients. Smoking increased the risk of lung cancer mortality among female patients only. HR for lung cancer mortality for those who smoked more than 40 pack-years compared to those who never smoked was 5.64 (95%CI = 1.43, 22.28) in women and 1.17 (95%CI = 0.61, 2.26) in men (p-interaction = 0.01) when adjusted for age, stage, and pathologic type. Multivitamin use also increased the risk of lung cancer mortality among female patients only. HR for lung cancer mortality for multivitamin users was 4.14(95%CI = 1.77, 9.73) in women and 1.46 (95%CI = 0.71, 3.00) in men (p-interaction = 0.17). The association between multivitamin use and lung cancer mortality was strongest among female non-smokers (HR = 4.10, 95%CI = 1.72, 9.77). In conclusion, smoking and multivitamin use worsen the survival of female lung cancer. Prognostic effect of multivitamin use may be stronger among non-smokers. Citation Format: Mi Yang, Hyun-Kyung Oh, Young Mog Shim, Myung-Hee Shin. Differential prognostic effect of smoking and multivitamin use on lung cancer survival by sex. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3418.

Background: Vitamin D may inhibit tumor progression by suppressing metastasis, proliferation, and angiogenesis. The vitamin D binding protein (DBP) is the primary carrier of circulating vitamin D compounds and functions in actin scavengering, macrophage activation, and neutrophil chemotaxis. Little is known about the association between vitamin D, DBP, and lung cancer survival. We investigated the association between serum concentrations of 25-hydroxyvitamin D (25(OH)D), DBP, and lung cancer mortality in 500 lung cancer cases from the ATBC Study. Methods: Serum concentrations of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free circulating vitamin D, were measured in fasting blood samples collected at baseline. Hazards ratios (HR) and 95% confidence intervals (CI) were used to estimate survival by quartiles of 25(OH)D, DBP, and the 25(OH)D:DBP molar ratio. Results: Median survival time was 0.5 years (IQR: 0.1 - 1.1) for 428 cases that died from lung cancer and 1.7 years (IQR: 0.1 - 7.8) for 72 lung cancer survivors. Median serum concentrations (nmol/L) of 25(OH)D and DBP were 33 (IQR: 20-50) and 5951 (IQR: 4725-7196), respectively, for lung cancer deaths and 37 (IQR: 22-52) and 5431 (IQR: 4600-7151), respectively, for lung cancer survivors. In multivariable adjusted models, higher concentrations of serum 25(OH)D were associated with a small but not statistically significant increase in lung cancer mortality (Q4 vs. Q1 HR = 1.20; 95% CI: 0.90, 1.60). Survival was not associated with higher serum concentrations of DBP (Q4 vs. Q1 HR = 1.01; 95% CI: 0.76, 1.34). A higher 25(OH)D:DBP molar ratio was associated with a slightly reduced risk of mortality, although not significant (Q4 vs. Q1 HR = 0.87; 95% CI: 0.65, 1.18). DBP concentration did not modify the association between 25(OH)D or the 25(OH)D:DBP molar ratio and lung cancer survival. In histology-specific analyses, elevated concentrations of 25(OH)D was associated with higher mortality in squamous cell carcinomas (HR = 1.47; 95% CI: 0.82, 2.65) and adenocarcinomas (HR = 1.42; 95% CI: 0.33, 6.05), but reduced mortality in small cell carcinomas (HR = 0.62; 95% CI: 0.18, 2.10). A higher 25(OH)D:DBP molar ratio was associated with higher mortality for squamous cell tumors (HR = 1.28; 95% CI: 0.68, 2.40), and lower mortality for adenocarcinomas (HR = 0.10; 95% CI: 0.02, 0.57) and small cell tumors (HR = 0.52; 95% CI: 0.12, 2.18). Associations between serum DBP and mortality were similar across histologic types. Conclusion: Higher vitamin D status was weakly associated with lung cancer survival and DBP was unrelated to survival; however, a higher 25(OH)D:DBP molar ratio indicative of unbound or “free” vitamin D may be related to increased adenocarcinoma and possibly small cell carcinoma survival. The findings should be evaluated in other longitudinal studies. Citation Format: Gabriella M. Anic, Stephanie J. Weinstein, Satu Männistö, Demetrius Albanes. Serum 25-hydroxyvitamin D, vitamin D binding protein, and lung cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2180. doi:10.1158/1538-7445.AM2014-2180

A longer menarche-to-first pregnancy window of susceptibility (WOS) is associated with increased breast cancer risk. Whether physical activity, an established preventive risk factor, during the menarche-to-first pregnancy WOS offsets breast cancer risk overall or for specific molecular subtypes is unclear. We examined the prospective association between physical activity during the menarche-to-first pregnancy WOS and breast cancer risk in the California Teachers Study (N = 78,940). Recreational physical activity at multiple timepoints were recalled at cohort entry, and converted to metabolic equivalent of task hours per week (MET-hrs/wk). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed 5,157 invasive breast cancer cases over 21.6years of follow-up. Longer menarche-to-first pregnancy WOS (≥ 20 vs. < 15years) was associated with higher breast cancer risk (HR = 1.23, 95% CI = 1.13-1.34). Women with higher physical activity level during menarche-to-first pregnancy had lower risk of invasive breast cancer (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.89, 95% CI = 0.83-0.97) and triple-negative subtype (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.53, 95% CI = 0.32-0.87). No association was observed for luminal A-like and luminal B-like subtypes. Higher physical activity level was associated with lower breast cancer risk among women with moderate (15-19years) menarche-to-first pregnancy intervals (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.80, 95% CI = 0.69-0.92), but not with short (< 15years) or long (≥ 20years) intervals. Physical activity during a WOS was associated with lower breast cancer risk in our cohort. Understanding timing of physical activity throughout the life course in relationship with breast cancer risk maybe important for cancer prevention strategies.

Background: Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. This study aims to assess the association between reproductive factors with lung cancer incidence and mortality among Asian women. Methods: A total of 308,949 female participants with a mean age of 55.13 from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) in the Asia Cohort Consortium (ACC) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). Results: A total of 3,119 primary lung cancer cases and 2,247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70 - 0.96) and 0.78 (95% CI = 0.65 - 0.94). Corresponding HRs were lowest among women with 1-2 children, with HRs of 0.78 (95% CI = 0.66 - 0.93) and 0.72 (95% CI = 0.59 - 0.87) for lung cancer incidence and mortality. The protective association of parity and lung cancer incidence was greater among ever-smokers (HR=0.66, 95% CI = 0.49 - 0.87) than in never-smokers (HR=0.90, 95% CI = 0.74 - 1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Compared with age at menopause &amp;lt;45 years, older age at menopause (≥55 years) was associated with a decreased risk of lung cancer mortality (HR=0.75, 95% CI = 0.58 - 0.96). Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.30, 95% CI = 1.01 - 1.67), compared to those who never used hormone replacements. Conclusions: Distinct from Western women, Asian parous women, especially those who have 1-2 children had a lower risk of lung cancer incidence and mortality compared with nulliparous women. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time. Citation Format: Xin Yin, Rie Kishida, Sarah Krull Abe, Md. Rashedul Islam, Md. Shafiur Rahman, Eiko Saito, Qing Lan, Batel Bletcher, Melissa Merritt, Ji-Yeob Choi, Aesun Shin, Ryoko Katagiri, Xiao-Ou Shu, Norie Sawada, Akiko Tamakoshi, Woon-Puay Koh, Ichiro Tsuji, Chisato Nagata, Sue K. Park, Sun-Seog Kweon, Yu-Tang Gao, Shoichiro Tsugane, Takashi Kimura, Jian-Min Yuan, Yukai Lu, Seiki Kanemura, Yumi Sugawara, Keiko Wada, Min-Ho Shin, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, Keitaro Matsuo, You-Lin Qiao, Nathaniel Rothman, Wei Zheng, Manami Inoue, Daehee Kang, Wei Jie Seow. Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia Cohort Consortium. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4200.

PURPOSE: Physical activity (PA) is associated with decreased breast cancer (BCa) risk. A longer menarche-to-first pregnancy window of susceptibility (WOS) is associated with increased BCa risk. Whether PA during the menarche-to-first pregnancy WOS offsets BCa risk is unclear. It is also unknown if differences in risk exist by BCa subtype. METHODS: We examined the prospective association between PA during the menarche-to-first pregnancy WOS and BCa risk in the California Teachers Study (N=78,940). Recreational PA levels from high school to current age, or, age 55, were recalled at cohort entry and converted to metabolic equivalent of task hours per week (MET-h/wk). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident invasive BCa for WOS and PA. RESULTS: 5,157 invasive BCa cases developed. The median length of follow-up was 21.6 years. Longer menarche-to-first pregnancy WOS (≥20 vs. <15 years) was associated with increased BCa risk (HR=1.23, 95% CI=1.13-1.34). Women with higher PA during menarche-to-first pregnancy WOS had decreased risk of invasive BCa (≥40 vs. <9 MET-h/wk: HR=0.89, 95% CI=0.83-0.97). The inverse association between PA during the menarche-to-first pregnancy WOS and BCa risk was strongest in triple-negative BCa (TNBC: ≥40 vs. <9 MET-h/wk: HR=0.53, 95% CI=0.32-0.87; luminal A-like: ≥40 vs. <9 MET-h/wk: HR=0.92, 95% CI=0.80-1.06; luminal B-like: ≥40 vs. <9 MET-h/wk: HR=0.84, 95% CI=0.52-1.36). Higher PA level during the menarche-to-first pregnancy WOS was associated with decreased BCa risk only among women with moderate (15-19 years) menarche-to-first pregnancy intervals (≥40 vs. <9 MET-h/wk: HR=0.80, 95% CI=0.69-0.92), but not women with short (<15 years; ≥40 vs. <9 MET-h/wk: HR=0.96, 95% CI=0.86-1,06) or long (≥20 years; ≥40 vs. <9 MET-h/wk: HR=0.93, 95% CI=0.74-1.17) intervals. CONCLUSION: PA during the menarche-to-first pregnancy WOS was associated with lower BCa risk in our cohort. Understanding the timing of PA over the life course in relationship to non-modifiable reproductive risk factors such as pregnancy maybe particularly important. Supported by NIH Grant U01 CA199277; P30 CA033572; P30 CA023100; UM1 CA164917; R01-CA077398; U54 CA155850; UL1 TR002014; UL1 TR000003; and KL2 TR002015.

Purpose: Cigarette smoking is the leading cause of lung cancer, but there exists a substantial proportion of lung cancer cases who have never smoked. Furthermore, lung cancer pathology, risk factors and prognosis differ by sex, prompting a need to investigate the influence of hormonal and reproductive factors. Most studies have shown a protective or no effect of postmenopausal hormone therapy (HT) on lung cancer risk, whereas the recent post-hoc analysis of the Women's Health Initiative showed that estrogen+progestin (E+P) decreased lung cancer survival. Given the substantial clinical implications, it is vital that the risk and survival associations be validated. Methods: We examined the associations between HT use and lung cancer risk and survival among 61,911 postmenopausal women enrolled in the California Teacher's Study. Between 1995 and 2007, 759 women (including 184 never smokers) were diagnosed with lung cancer; 425 of these died. Age-stratified, multivariable Cox proportional hazards regression was used to calculate hazard ratios (HR). Results: After adjusting for potential confounders, overall HT use was not associated with lung cancer risk. Among ever-smoking women, recent use of estrogen (E) or E+P at baseline was associated with decreased lung cancer risk (HR, 0.80; 95% confidence interval (CI), 0.66–0.96). However, the same association was not observed among never smokers (HR, 1.10; 95% CI, 0.78–1.55). Among ever-smoking women, using HT (E or E+P) for a duration of less than 5 years or 5–15 years was associated with decreases in risk (HR, 0.78, 95% CI, 0.61–0.99; HR, 0.69, 95% CI, 0.53–0.88, respectively). Additionally, recent use of E+P, but not E, was associated with decreased risk (HR, 0.76; 95% CI, 0.60–0.96; HR, 0.81, 95% CI, 0.62–1.06; respectively). After adjusting for potential confounders, any HT use (vs. no use) was associated with an increase in lung cancer survival (HR, 0.76; 95% CI, 0.60–0.95), with no difference by smoking status. The median survival time (MST) for ever users of HT was 47.7 months, compared to 37.8 months among never users (log-rank p=0.005). Among patients diagnosed with non-small cell lung cancer the difference was greater (HT ever user, MST=56.2 months vs. HT never user, MST= 39.9 months; log-rank p=0.002). Statistically significant increases in lung cancer survival were seen among recent E users (HR, 0.72; 95% CI, 0.55–0.96), but no survival difference was observed among E+P users. For E users overall, longer duration of E was associated with improved survival (0–5 years: HR, 0.81, 95% CI, 0.56–1.67; 5–15 years: HR, 0.65, 95% CI, 0.42–1.17; &amp;gt;15 years: HR, 0.66, 95% CI, 0.45–0.97; trend p=0.011). Conclusions: In contrast to recent findings, our results suggest that postmenopausal E+P use is associated with decreased lung cancer risk among ever smokers, while E use is associated with increased lung cancer survival overall. These results further reveal the complex nature of the role of hormonal factors in the etiology and prognosis of lung cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B130.

Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50-79 years between 1993 and 1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)-min/week: none <100 (reference), low 100 to <500, medium 500 to <1,200, high 1,200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow-up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared with no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p = 0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76-0.96); medium, HR: 0.82 (0.73-0.93); and high, HR: 0.90 (0.79-1.03)], and mortality [p < 0.0001; low, HR: 0.80 (0.69-0.92); medium, HR: 0.68 (0.59-0.80); and high, HR: 0.78 (0.66-0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p = 0.01), with a stronger association in women with BMI < 30 kg/m(2) . Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non-obese women.

This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer. To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations. We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews. We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer. Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach. In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence). Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.

Purpose: Racial disparities in survival persist in patients with early-stage non-small cell lung cancer (NSCLC). Possible contributors to these disparities are stage at diagnosis, comorbidities, and socioeconomic factors. The goal of this study is to compare differences in survival between black and white patients from veteran and non-veteran populations, while accounting for treatment. Methods: Black and white men aged ≥65 years diagnosed with stage I NSCLC from 2001-2009 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and Veterans Affairs (VA) cancer registry. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for differences between black and white patients in postoperative mortality among surgery patients, 5-year overall survival (OS), and lung cancer specific survival (LCSS). Results: There were 8,744 and 7,895 patients in the SEER and VA cohorts, respectively. Overall, black patients were less likely to be treated than white patients (74% vs 85% in SEER, p&amp;lt;0.0001; 69% vs 77% in VA, p&amp;lt;0.0001), and among treated patients, to receive surgery only (47% vs 62% in SEER, p&amp;lt;0.0001; 55% vs 62%, p=0.0007 in VA). OS was worse for black compared to white patients after adjustment for demographic and clinical factors (HR: 1.17, 95% CI: 1.06-1.30 in SEER; HR: 1.08, 95% CI: 1.00-1.16 in VA). However, there was no difference in OS when also adjusting for treatment (HR: 0.99, 95% CI: 0.89-1.09 in SEER; HR: 0.97, 95% CI: 0.91-1.05 in VA). For LCSS, the HRs for black vs. white patients were 1.21 (95% CI 1.07-1.37) in SEER and 1.06 (95% CI 0.96-1.17) in VA, when adjusting for demographic and clinical factors. LCSS HRs were not statistically significant in either cohort when also adjusting for treatment (HR: 0.99, 95% CI: 0.87-1.12 in SEER; HR: 0.93, 95% CI: 0.85-1.02 in VA). Similar results were obtained when analyses were restricted to patients receiving treatment, accounting for treatment modality. Among patients receiving surgery only, adjusted OS was similar across races (HR: 1.11, 95% CI: 0.91-1.36 in SEER; HR: 1.08, 95% CI: 0.95-1.23 in VA). There was no significant difference in postoperative 30-day survival in black vs. white patients (HR: 1.57, 95% CI: 0.99-2.49 in SEER; HR: 1.10, 95% CI: 0.71-1.70 in VA), nor in postoperative 90 day survival (HR: 1.28, 95% CI: 0.87-1.89 in SEER; HR: 0.90, 95% CI: 0.63-1.29 in VA). Conclusion: Among older stage I NSCLC patients, no significant racial differences in overall or lung cancer survival were detected in VA or SEER cohorts when accounting for treatment, despite observing racial differences in receipt of treatment in both populations. This suggests that survival disparities are significantly reduced when black and white patients receive similar treatment, even in populations covered by different health care systems. Effort to facilitate stage appropriate treatment in minority patients should be initiated. Citation Format: Naomi D. Alpert, Christina D. Williams, Thomas Redding, A. Jasmine Bullard, Raja Flores, Emanuela Taioli. Racial differences in survival among veterans and nonveteran populations with stage I non-small cell lung cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B007.

Background: Pancreatic cancer is highly fatal; thus, preventive strategies are needed. Besides cessation of cigarette smoking, physical activity may reduce pancreatic cancer risk by improving insulin sensitivity and glucose tolerance. However, the existing data lack consistency and generally, physical activity has been measured only at one time point. We examined recreational physical activity during different periods of life as well as a cumulative, long-term physical activity measure in relation to the risk of pancreatic cancer in California Teachers Study (CTS). Methods: 120,921 women aged 22-84 years participating in the CTS with no history of pancreatic cancer were followed from 1995 through 2011. The self-administered baseline (1995-1996) questionnaire captured information on demographics, moderate and strenuous recreational physical activity during high school, between ages 18 and 24, 25 and 34, 35 and 44, and 45 and 54 years, and in the three years before baseline, and potential risk factors for pancreatic cancer such as body mass index (BMI), diabetes, alcohol consumption, cigarette smoking, and dietary fat intake. Incident diagnoses of invasive pancreatic cancer were identified through annual linkages with the California Cancer Registry. We calculated average number of hours per week for recreational physical activity during different periods of life and combined them into a long-term physical activity measure. We fit Cox proportional hazards models to data to estimate the hazard ratios (HR) of pancreatic cancer risk and their corresponding 95% confidence intervals (CI) associated with moderate and strenuous physical activity in each age/time period and over the “long-term.” For each analysis, the least active group (≤0.5 hours/week) served as the reference group. Multivariable models were stratified by age at baseline (in single years) and were adjusted for race, total pack-years of cigarette smoking, alcohol consumption and total dietary fat intake in the year before baseline, diabetes, and BMI at baseline. Furthermore, we tested for a linear trend in risk by fitting the median value of physical activity within each category; we also examined whether BMI, smoking status, and alcohol intake modified any physical activity association. Results: During 1,715,690 person-years of follow-up, 429 women were diagnosed with invasive pancreatic cancer. The average age at diagnosis of pancreatic cancer was 74 years. In the multivariable model, women with higher levels of long-term moderate/strenuous physical activity had lower risk of pancreatic cancer than the least active women (≤0.5 hours/week) although the 95% CI included one (2.51-5.5 hours/week: HR=0.76; 95% CI=0.56-1.02, &amp;gt;5.5 hours/week: HR=0.85; 95% CI=0.63-1.15) and no linear trend in pancreatic cancer risk was observed (Ptrend=0.35). In the analysis of physical activity during different periods of life, we observed a marginally significant decreasing trend in risk with increasing physical activity during ages 18-24 years (Ptrend=0.05). The stratified analysis indicated a decreasing trend in pancreatic cancer risk with increasing physical activity during ages 18-24 years among women who were overweight or obese at baseline (Ptrend=0.006), who never smoked cigarettes (Ptrend=0.02), and who consumed &amp;lt;10 grams of alcohol per day in the year before baseline (Ptrend=0.02). No significant effect modifications were observed. Conclusions: The CTS data suggest that a higher level of recreational physical activity in early adulthood modestly reduces the risk of pancreatic cancer development in subgroups of women. However, we lacked sufficient statistical power to demonstrate effect modification. Larger studies are needed to understand whether the effect of physical activity on pancreatic cancer varies by age at activity, BMI, smoking status, or alcohol intake. Citation Format: Kayo Togawa, Huiyan Ma, Jane Sullivan-Halley, Jessica Clague, Susan Neuhausen, Eunjung Lee, Dennis Deapen, Leslie Bernstein. Recreational physical activity and the risk of pancreatic cancer in the California Teachers Study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A36.

This study aimed to evaluate the association of a healthy lifestyle pattern with mortality risk among patients with type 2 diabetes mellitus (T2DM). Data were derived from a prospective cohort study enrolling 13776 Chinese patients with T2DM. A healthy lifestyle pattern was constructed based on six lifestyle factors, including smoking status, alcohol consumption, dietary habits, physical activity, sedentary time, and sleep duration. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. During a median follow-up of 9.78 years, 2497 deaths were recorded. Compared with T2DM patients with a lifestyle pattern scoring 0–2, those scoring 5–6 had a 40% lower risk for all-cause mortality (HR = 0.60, 95% CI: 0.52–0.69), a 33% lower risk for cardiovascular disease mortality (HR = 0.67, 95% CI: 0.52–0.86), and a 25% lower risk for cancer mortality (HR = 0.75, 95% CI: 0.58–0.97). Additionally, we found that the association between the lifestyle pattern and all-cause mortality risk was stronger in females than in males (P for interaction < 0.05). In conclusion, adherence to a healthy lifestyle pattern is associated with a decreased risk of all-cause, cardiovascular disease, and cancer mortality. These findings have important implications for reducing premature mortality among patients with T2DM.

BackgroundPrior research has not examined the connection between the quality of macronutrients and the occurrence as well as fatality rates of lung cancer (LC). Consequently, to delve deeper into the correlations between macronutrient quality and the likelihood of developing LC, we carried out an extensive, long-term prospective cohort study of 101,755 American adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.MethodsOur research cohort comprised 154,887 adults, aged between 55 and 74, who were enrolled from 10 screening facilities across the United States. The macronutrient quality index (MQI) was derived from participants’ responses to a dietary history questionnaire (DHQ). To quantify the strength and precision of the relationships between MQI and the incidence as well as mortality of LC, we employed Cox proportional hazards regression modeling to estimate hazard ratios (HRs) alongside their corresponding 95% confidence intervals (CIs). Additionally, we conducted subgroup analyses to scrutinize whether the observed link between MQI and LC risk was subject to modification by potential confounding variables. To reinforce the reliability of our results, sensitivity analyses were also carried out.ResultsOver an average follow-up period spanning 8.82 ± 1.95 years (accumulating to 897,809 person-years of observation), we recorded 1,706 LC diagnoses, encompassing 1,464 cases of non-small cell lung cancer (NSCLC) and 242 cases of small cell lung cancer (SCLC). Additionally, there were 1,217 deaths attributed to LC, with 1,005 NSCLC-related and 212 SCLC-related fatalities. Our results demonstrate a distinct, statistically significant inverse association between a higher MQI and both a reduced incidence (HR Q4 vs. Q1: 0.65; 95% CI: 0.56–0.76; p < 0.001 for trend) and decreased mortality (HR Q4 vs. Q1: 0.71; 95% CI: 0.60–0.84; p < 0.001 for trend) of LC. This inverse relationship held true for both NSCLC and SCLC subtypes. The robustness of the associations between MQI and the incidence as well as mortality of LC was solidly affirmed through sensitivity analyses.ConclusionOur research outcomes imply that prioritizing the intake of higher-quality macronutrients could serve as a viable strategy to mitigate LC risk within the American population.