Alcohol consumption and risk of melanoma and non-melanoma skin cancer in the Women’s Health Initiative

Purpose

The relationship between alcohol consumption and preference of alcohol type with hazard of melanoma (MM) and risk of non-melanoma skin cancer (NMSC) was examined in the Women’s Health Initiative (WHI) Observational Study (OS).

Methods

A prospective cohort of 59,575 White postmenopausal women in the WHI OS (mean age 63.6) was analyzed. Cox proportional hazards models and logistic regression techniques were used to assess the hazard and risk of physician-adjudicated MM and self-reported NMSC, respectively, after adjusting for potential confounders including measures of sun exposure and skin type.

Results

Over 10.2 mean years of follow-up, 532 MM cases and 9,593 NMSC cases occurred. A significant relationship between amount of alcohol consumed and both MM and NMSC was observed, with those who consume 7+ drinks per week having a higher hazard of MM (HR 1.64 (1.09, 2.49), p _global = 0.0013) and higher risk of NMSC (OR 1.23 (1.11, 1.36), p _global < 0.0001) compared to non-drinkers. Lifetime alcohol consumption was also positively associated with hazard of MM (p = 0.0011) and risk of NMSC (p < 0.0001). Further, compared to non-drinkers, a preference for either white wine or liquor was associated with an increased hazard of MM (HR 1.52 (1.02, 2.27) for white wine; HR 1.65 (1.07, 2.55) for liquor) and risk of NMSC (OR 1.16 (1.05, 1.28) for white wine; OR 1.26 (1.13, 1.41) for liquor).

Conclusions

Higher current alcohol consumption, higher lifetime alcohol consumption, and a preference for white wine or liquor were associated with increased hazard of MM and risk of NMSC.     

The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study

Purpose

Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women’s Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches.

Methods

To identify candidate gene–statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study.

Results

After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches.

Conclusions

We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women’s Health Initiative.

     

Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women’s Health Initiative

Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women’s Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) (www.affymetrix.com) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059–1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.     

C-reactive protein concentration and risk of selected obesity-related cancers in the Women’s Health Initiative

Background

Obesity is a chronic inflammatory condition strongly associated with the risk of numerous cancers. We examined the association between circulating high-sensitivity C-reactive protein (hsCRP), a biomarker of inflammation and strong correlate of obesity, and the risk of three understudied obesity-related cancers in postmenopausal women: ovarian cancer, kidney cancer, and multiple myeloma.

Methods

Participants were 24,205 postmenopausal women who had measurements of baseline serum hsCRP (mg/L) in the Women’s Health Initiative (WHI) CVD Biomarkers Cohort, a collection of four sub-studies within the WHI. Incident cancers were identified over 17.9 years of follow-up (n?=?153 ovarian, n?=?110 kidney, n?=?137 multiple myeloma). hsCRP was categorized into study-specific quartiles. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of baseline hsCRP with the risk of these cancers.

Results

There was no clear association between baseline hsCRP concentration and the risk of ovarian cancer (quartile 4 vs. 1: HR 0.87, 95% CI 0.56–1.37), kidney cancer (HR 0.95, 95% CI 0.56–1.61), or multiple myeloma (HR 0.82, 95% CI 0.52–1.29). HRs for 1 mg/L increases in hsCRP also approximated the null value for each cancer.

Conclusions

The results of this study suggest that elevated CRP is not a major risk factor for these obesity-related cancers (ovarian or kidney cancers, or multiple myeloma) among postmenopausal women. Given the importance of elucidating the mechanisms underlying the association of obesity with cancer risk, further analysis with expanded biomarkers and in larger or pooled prospective cohorts is warranted.

     

Family history of cancer and risk of breast cancer in the Black Women’s Health Study

Introduction  

Relatively little research has been conducted on familial breast cancer in African American women.     

Abuse victimization and risk of breast cancer in the Black Women’s Health Study

Few studies have examined the relation between abuse victimization and breast cancer, and results have been inconclusive. Using data from 35,728 participants in the Black Women’s Health Study, we conducted multivariable Cox regression to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CI) for the association of abuse across the life span (childhood, adolescence, and adulthood) with breast cancer. Incident breast cancer diagnoses were reported during 1995–2009, and abuse histories were reported in 2005. No associations were found between abuse victimization in either childhood or adolescence and breast cancer. We found a weak positive association between abuse in adulthood and breast cancer (IRR = 1.18, 95% CI = 1.03–1.34). IRRs for physical abuse only, sexual abuse only, and both physical and sexual abuse in adulthood, relative to no abuse, were 1.28 (95% CI = 1.09–1.49), 0.96 (95% CI = 0.76–1.20), and 1.22 (95% CI = 1.00–1.49), respectively. IRRs for low, intermediate, and high frequencies of physical abuse in adulthood, relative to no abuse, were 1.28 (95% CI = 1.07–1.52), 1.37 (95% CI = 1.04–1.79), and 1.24 (95% CI = 0.95–1.62), respectively. Our data suggest an increased risk of breast cancer among African-American women who reported physical abuse in adulthood, but there was little evidence of a dose–response relation. These results require confirmation in other studies.     

Cigarette smoking and risk of benign proliferative epithelial disorders of the breast in the Women’s Health Initiative

Objective To investigate the association between cigarette smoking and risk of benign proliferative epithelial disorders (BPED) of the breast. Methods We used data from an ancillary study of benign breast disease that is being conducted in the Women’s Health Initiative randomized clinical trials among 68,132 postmenopausal women aged 50–79 at recruitment. After following the trial participants for an average of 7.8 years, we had ascertained 294 incident cases with atypical hyperplasia and 1,498 incident cases with non-atypical BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios for the association between cigarette smoking and risk of BPED. Results Smoking measures, including duration of smoking, intensity of smoking, pack-years of smoking, age at which smoking commenced, and years since quitting smoking, were not associated with risk of BPED overall or by histological subtypes. Conclusion The null association between cigarette smoking and risk of BPED of the breast suggests that the carcinogenic and antiestrogenic effects of cigarette smoking on the breast might counterbalance each other and that cigarette smoking might have no overall effects on BPED of the breast among postmenopausal women.     

History of periodontal disease diagnosis and lung cancer incidence in the Women’s Health Initiative Observational Study

Purpose

While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women.

Methods

Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was self-reported, and 754 incident lung cancer cases occurred during an average 6.8 (SD ± 2.6) years of follow-up. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).

Results

Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR 1.24, 95 % CI 1.07–1.45). There was a positive additive interaction between PD with pack-years of smoking (p = 0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95 % CI 0.68–1.53).

Conclusions

Periodontal disease was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.     

Dietary carbohydrate, glycemic index, and glycemic load in relation to colorectal cancer risk in the Women’s Health Initiative

Evidence implicating hyperinsulinemia and insulin resistance in the etiology of colorectal cancer suggests that a diet characterized by a high glycemic index and load may increase the risk of this disease, but previous studies have yielded inconsistent results. We assessed the association between intake of total carbohydrates, sugars, fiber, and the glycemic index (GI) and glycemic load (GL) of individual diets, and risk of developing colorectal cancer among 158,800 participants in the Women’s Health Initiative (WHI). We used a GI/GL database developed specifically for the WHI food-frequency questionnaire. Over an average of 7.8 years of follow-up, 1,476 incident cases of colorectal cancer were identified. Cox proportional hazards models were used to estimate the association between dietary factors classified by quintiles and risk of colorectal cancer, with adjustment for covariates. Total carbohydrate intake, glycemic index, glycemic load, and intake of sugars and fiber showed no association with colorectal cancer. Analyses by cancer subsite also yielded null results, with the exception of a borderline positive association between glycemic load and rectal cancer (HR for the highest versus lowest quintile 1.84, 95% confidence interval 0.95–3.56, p for trend 0.05). Analyses stratified by tertiles of body mass index and physical activity showed no evidence of effect modification by these factors. Results of this large study do not support of a role of a diet characterized by high glycemic index or load in colorectal carcinogenesis in postmenopausal women. S. A. A. Beresford, B. Caan, M. L. Neuhouser, and L. F. Tinker are for the Women’s Health Initiative Investigators.     

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women’s Health Across the Nation

Purpose

Two case–control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer.

Methods

We evaluated this relationship in the longitudinal Study of Women’s Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment.

Results

Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77).

Conclusion

VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

     

Tea and coffee intake in relation to risk of breast cancer in the Black Women’s Health Study

Objective

Prospective studies of tea and coffee intake and breast cancer risk have yielded inconsistent results. None of these studies has reported separately on African-American women. We prospectively examined the relation of tea and coffee consumption to risk of breast cancer among 52,062 women aged 21–69 at enrollment in 1995 in the Black Women’s Health Study.

Methods

Dietary intake was assessed in 1995 and 2001 using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for breast cancer risk factors.

Results

During 12 years of follow-up through 2007, there were 1,268 incident cases of breast cancer. Intakes of tea, coffee, and caffeine were not significantly associated with the risk of breast cancer overall. The IRRs for consumption of ≥4 cups/day compared with none were 1.13 (95% CI 0.78–1.63) for tea and 1.03 (95% CI 0.77–1.39) for caffeinated coffee, and the IRR for the top quintile relative to the bottom quintile of caffeine intake was 1.04 (95% CI 0.87–1.24). Consumption of tea, coffee, and caffeine was not significantly associated with breast cancer risk according to menopausal status or hormone receptor status.

Conclusion

Our findings suggest that intakes of tea, coffee, and caffeine are not associated with the risk of breast cancer among African-American women.     

Association between psoriasis and incident cancer: the Iowa’s Women’s Health Study

Introduction  

Studies have reported higher cancer risk in individuals with psoriasis, a chronic inflammatory autoimmune disease; however, adjustment for potential confounders was lacking.     

Coffee and caffeine intake and the risk of ovarian cancer: the Iowa Women’s Health Study

Laboratory data suggest that caffeine or some components of coffee may cause DNA mutations and inhibit tumor suppressor mechanisms, leading to neoplastic growth. However, coffee consumption has not been clearly implicated in the etiology of human postmenopausal ovarian cancer. This study evaluated the relationship of coffee and caffeine intake with risk of epithelial ovarian cancer in a prospective cohort study of 29,060 postmenopausal women. The participants completed a mailed questionnaire that assessed diet and health history and were followed for ovarian cancer incidence from 1986 to 2004. Age-adjusted and multivariate-adjusted hazard ratios were calculated for four exposure variables: caffeinated coffee, decaffeinated coffee, total coffee, and total caffeine to assess whether or not coffee or caffeine influences the risk of ovarian cancer. An increased risk was observed in the multivariate model for women who reported drinking five or more cups/day of caffeinated coffee compared to women who reported drinking none (HR = 1.81, 95% CI: 1.10–2.95). Decaffeinated coffee, total coffee, and caffeine were not statistically significantly associated with ovarian cancer incidence. Our results suggest that a component of coffee other than caffeine, or in combination with caffeine, may be associated with increased risk of ovarian cancer in postmenopausal women who drink five or more cups of coffee a day.     

Consumption of dairy and meat in relation to breast cancer risk in the Black Women’s Health Study

Purpose

Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study.

Methods

In the Black Women’s Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models.

Results

Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74–1.46 comparing ≥1,000–0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85–1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (?), progesterone receptor (PR) +, PR?, ER+/PR+, and ER?/PR? breast cancer were generally null.

Conclusions

This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.     

Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women’s Health Initiative observational study

An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women’s Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50–79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95–1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01–1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05–1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.     

Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian,postmenopausal women in the Women’s Health Initiative

Background

Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.

Objective

Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.

Methods

Women were followed with yearly surveys throughout the duration of their participation in the Women’s Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.

Results

Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.

Conclusion

This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

     

Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study

Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation activity, is thought to act as a cancer chemopreventive agent. This study evaluated the association between vitamin D intake and breast cancer risk among women in a large prospective cohort study. A total of 34,321 postmenopausal women who had completed a questionnaire that included diet and supplement use were followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for breast cancer were calculated for dietary, supplemental, and total vitamin D intake among all women. The adjusted RR of breast cancer for women consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77–1.03). RRs were stronger among women with negative than positive ER or PR status. The association of high vitamin D intake with breast cancer was strongest in the first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46–0.94 compared with lowest-intake group), and diminished over time. Changes in vitamin D intake over time might have contributed to the diminished association observed in later years. Vitamin D intake of >800 IU/day appears to be associated with a small decrease in risk of breast cancer among postmenopausal women. Studies evaluating all sources of vitamin D, especially sun exposure, are needed to fully understand the association between vitamin D and breast cancer risk.