Ange Wang

Statin use and all-cancer survival: prospective results from the Women’s Health Initiative

Background:This study aims to investigate the association between statin use and all-cancer survival in a prospective cohort of postmenopausal women, using data from the Women’s Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT).Methods:The WHI study enrolled women aged 50–79 years from 1993 to 1998 at 40 US clinical centres. Among 146 326 participants with median 14.6 follow-up years, 23 067 incident cancers and 3152 cancer deaths were observed. Multivariable-adjusted Cox proportional hazards models were used to investigate the relationship between statin use and cancer survival.Results:Compared with never-users, current statin use was associated with significantly lower risk of cancer death (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.71–0.86, P<0.001) and all-cause mortality (HR, 0.80; 95% CI, 0.74–0.88). Use of other lipid-lowering medications was also associated with increased cancer survival (P-interaction (int)=0.57). The lower risk of cancer death was not dependent on statin potency (P-int=0.22), lipophilicity/hydrophilicity (P-int=0.43), type (P-int=0.34) or duration (P-int=0.33). However, past statin users were not at lower risk of cancer death compared with never-users (HR, 1.06; 95% CI, 0.85–1.33); in addition, statin use was not associated with a reduction of overall cancer incidence despite its effect on survival (HR, 0.96; 95% CI, 0.92–1.001).Conclusions:In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications was associated with decreased cancer death, regardless of the type, duration, or potency of statin medications used.

Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort

BACKGROUND Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work). PATIENTS AND METHODS The Womens Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status. RESULTS Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58). CONCLUSIONS In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking. CLINICALTRIALS.GOV: NCT00000611.BACKGROUND Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work). PATIENTS AND METHODS The Womens Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status. RESULTS Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58). CONCLUSIONS In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking. CLINICALTRIALS.GOV: NCT00000611.

Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women’s Health Initiative

PURPOSE This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Womens Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers. METHODS Lung cancer diagnoses were centrally adjudicated by pathology review. Baseline survey questionnaires collected sociodemographic and health information. Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age, education, calcium/vitamin D, body mass index, smoking (status, age at start, duration, and pack-years), alcohol, family history, oral contraceptive, hormones, physical activity, and diet. RESULTS The cohort included 129,951 women--108,487 (83%) non-Hispanic white (NHW); 10,892 (8%) non-Hispanic black (NHB); 4,882 (4%) Hispanic; 3,696 (3%) Asian/Pacific Islander (API); 534 (< 1%) American Indian/Alaskan Native; and 1,994 (1%) other. In unadjusted models, Hispanics had 66% lower odds of lung cancer compared with NHW (odds ratio [OR], 0.34; 95% CI, 0.2 to 0.5), followed by API (OR, 0.45; 95% CI, 0.27 to 0.75) and NHB (OR, 0.75; 95% CI, 0.59 to 0.95). In fully adjusted multivariable models, the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null (OR, 0.59; 95% CI, 0.35 to 0.99). In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women (OR, 0.30 [95% CI, 0.15 to 0.62] and 0.34 [95% CI, 0.16 to 0.75, respectively); however, no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models. CONCLUSION Differences in lung cancer incidence and mortality are associated with sociodemographic, clinical, and behavioral factors. These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women. Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality.

Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative.

Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Womens 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/m2. 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.

Protective Effects of Statins in Cancer: Should They Be Prescribed for High-Risk Patients?

Purpose of ReviewStatins are one of the most widely prescribed drug classes in the USA. This review aims to summarize recent research on the relationship between statin use and cancer outcomes, in the context of clinical guidelines for statin use in patients with cancer or who are at high risk for cancer.Recent FindingsA growing body of research has investigated the relationship between statins and cancer with mixed results. Cancer incidence has been more extensively studied than cancer survival, though results are inconsistent as some large meta-analyses have not found an association, while other studies have reported improved cancer outcomes with the use of statins. Additionally, two large studies reported increased all-cancer survival with statin use. Studies on specific cancer types in relation to cancer use have also been mixed, though the most promising results appear to be found in gastrointestinal cancers. Few studies have reported an increased risk of cancer incidence or decreased survival with statin use, though this type of association has been more commonly reported for cutaneous cancers.SummaryThe overall literature on statins in relation to cancer incidence and survival is mixed, and additional research is warranted before any changes in clinical guidelines can be recommended. Future research areas include randomized controlled trials, studies on specific cancer types in relation to statin use, studies on populations without clinical indication for statins, elucidation of underlying biological mechanisms, and investigation of different statin types. However, studies seem to suggest that statins may be protective and are not likely to be harmful in the setting of cancer, suggesting that cancer patients who already take statins should not have this medication discontinued.

Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative.

Background:The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women’s Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women.Methods:The WHI study enrolled women aged 50–79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models.Results:Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (ORadj) 1.21; 95% confidence interval (CI): 1.07–1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08–2.16), simvastatin (OR 1.38; 95% CI: 1.12–1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18–1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin–NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history.Conclusions:Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration–effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship.

Differences in Active and Passive Smoking Exposures and Lung Cancer Incidence Between Veterans and Non-Veterans in the Women’s Health Initiative

INTRODUCTION Women Veterans may have higher rates of both active and passive tobacco exposure than their civilian counterparts, thereby increasing their risk for lung cancer. PURPOSE OF THE STUDY To compare differences in active and passive smoking exposure and lung cancer incidence among women Veterans and non-Veterans using prospective data from the Womens Health Initiative (WHI). DESIGN AND METHODS We used data from the WHI, which collected longitudinal demographic, clinical, and laboratory data on 161,808 postmenopausal women. We employed linear and multinomial regression and generalized linear models to compare active and passive smoking exposure between Veterans and non-Veterans and Cox proportional hazards models to estimate differences in lung cancer incidence rates. RESULTS After adjustment, Veterans had 2.54 additional pack years of smoking compared with non-Veterans (95% confidence interval [CI] 1.68, 3.40). Veterans also had a 1% increase in risk of any passive smoking exposure (95% CI 1.00, 1.02) and a 9% increase in risk of any workplace exposure (95% CI 1.07, 1.11) compared with non-Veterans. After adjustment for age and smoking exposures, Veterans did not have a higher risk of lung cancer compared with non-Veterans (relative risk = 1.06 95% CI 0.86, 1.30). IMPLICATIONS Women Veterans had higher rates of tobacco use and exposure to passive smoking, which were associated with a higher risk for lung cancer compared with non-Veterans. Clinicians who care for Veterans need to be aware that older women Veterans have more exposures to risk factors for lung cancer.

Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans

Background Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene–environment interactions is not well understood. Methods We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Womens Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case–control study of African-American females and males (1078 lung cancer cases and 822 controls). Findings Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10− 5). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = − 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. Interpretation These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

Hypertension: Do calcium-channel blockers increase breast cancer risk?

A case–control study of five classes of antihypertensive medication used among 2,851 women shows that taking calcium-channel blockers for ≥10 years is associated with increased risk of invasive ductal and lobular breast carcinoma. These results are intriguing, but warrant additional investigation given the study limitations and inconsistent findings in the literature.

Association of non‐melanoma skin cancer with second non‐cutaneous malignancy in the Women's Health Initiative

DEAR EDITOR, Nonmelanoma skin cancer (NMSC), the most prevalent cancer in the U.S.A., has been associated with increased risk of noncutaneous malignancies, including breast cancer, lung cancer and lymphoma. In the Women’s Health Initiative (WHI) Observational Study (OS), women with NMSC history at baseline were more likely to report history of another cancer [odds ratio 2 3, 95% confidence interval (CI) 2 18– 2 44]. Subsequently, Nurses Health Study prospective analyses found an increased risk of developing breast cancer, lung cancer and melanoma in women with NMSC. We sought to replicate these prospective findings in the large WHI cohort, for which important potential confounding factors, e.g. smoking and body mass index (BMI), and rich phenotypic data are available. The design, eligibility criteria and recruitment methods of the WHI OS (n = 93 676) and clinical trial (CT; n = 68 132) cohorts of postmenopausal women, aged 50–79 years, have been described previously. History of NMSC did not exclude enrollment in the WHI, whereas history of any other cancer diagnosis within 10 years of was an exclusion criterion from study enrollment. Detailed demographic and cancer risk factors were collected at baseline (1993–98) and at 3 years by interview, questionnaire and physical examination. Only white women were included in these analyses resulting in an analytic cohort of 121 619. All cancer diagnoses through August 2014 were reported by annual questionnaire. Medical records and additional information were obtained to adjudicate cancers. The base model was adjusted solely for age and BMI (< 25, 25–30, > 30). Further models were adjusted for family history of any cancer and selected cancer-specific risk factors, such as antihormone therapy for breast cancer. Specific adjustment variables are listed in Table 1. Cox proportional hazard analyses were performed, starting at enrolment. Hazard ratios (HRs) were estimated for development of any (all cancers combined except NMSC) and sitespecific cancers. All tests were two-sided with P < 0 05. General characteristics of the study population by history of NMSC at baseline are shown in Table 2. Compared with women with no NMSC history at baseline, women with NMSC history were more likely to be older (age 70–79 years), reside in southern and western geographic regions, burn but not tan, and less likely to be obese; in addition, a higher proportion reported family history of any cancer. Reported time spent outdoors in summer as a child did not differ. In ageand BMI-adjusted models (Table 3), NMSC history at baseline was associated with a higher risk of any cancer diagnosis (all cancers except NMSC: HR 1 20, 95% CI 1 20– 1 30), breast cancer (HR 1 21, 95% CI 1 13–1 30), lung cancer (HR 1 26, 95% CI 1 12–1 42), melanoma (HR 2 42,