Brenda M Birmann

Menstrual cycle characteristics and incident cancer: a prospective cohort study

AbstractSTUDY QUESTIONAre menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?SUMMARY ANSWERIrregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.WHAT IS KNOWN ALREADYLong and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.STUDY DESIGN, SIZE, DURATIONProspective cohort study. Prospective follow-up of 78 943 women participating in the Nurses’ Health Study II between 1989 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSWe followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14–17, 18–22 and 29–46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.MAIN RESULTS AND THE ROLE OF CHANCEWe documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29–46 years had an 11% (95% CI: 2–21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9–39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09–1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14–17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02–1.81).LIMITATIONS, REASONS FOR CAUTIONOur study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.WIDER IMPLICATIONS OF THE FINDINGSWomen with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.STUDY FUNDING/COMPETING INTERESTThis work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.

Personal use of permanent hair dyes and cancer risk and mortality in US women: prospective cohort study

AbstractObjectiveTo evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality.DesignProspective cohort study.Setting and participants117 200 women enrolled in the Nurses’ Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years.ExposureStatus, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes.Main outcome measuresAssociations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models.ResultsEver users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair.ConclusionNo positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.

Circulating Biomarkers of Inflammation and Ovarian Cancer Risk in the Nurses' Health Studies

AbstractBackground:Chronic inflammation is a well-established mechanism of ovarian carcinogenesis; however, the specific immunogenic processes influencing ovarian tumor development remain unclear. In a case–control study nested within the Nurses' Health Study (NHS) and the NHSII, we examined the association between six inflammatory chemokines and cytokines [B-cell activating factor (BAFF), C-X-C motif chemokine ligand 13 (CXCL13), IL8, soluble(s)IL2-receptor-α(Rα), sIL6Rα] and epithelial ovarian cancer risk.Methods:Among 299 epithelial ovarian cancer cases and 334 matched controls, six inflammatory biomarkers were measured in plasma collected 1–24 years before diagnosis or index date using two custom multiplex Luminex panels. ORs and 95% confidence intervals (CI) were estimated for the association between each biomarker and risk using multivariable conditional logistic regression with adjustment for relevant confounders. We additionally assessed heterogeneity in the risk associations by histotype [high-grade serous carcinoma (HGSC) vs. non-HGSC], body mass index, smoking status, menopausal status, and aspirin use.Results:Women with the highest versus lowest quartile (Q) levels of CXCL13 had a 72% increased ovarian cancer risk (OR = 1.72; 95% CI = 1.04–2.83; Ptrend = 0.007). The positive association with CXCL13 was stronger in magnitude for non-HGSC, overweight or obese women, and postmenopausal women, although only menopausal status demonstrated statistically significant heterogeneity (Pinteraction = 0.04). The remaining biomarkers were not associated with risk.Conclusions:This first evidence that prediagnostic CXCL13, a B-cell chemoattractant, is associated with an increased risk of epithelial ovarian cancer expands current understanding of the role of inflammation in ovarian carcinogenesis.Impact:CXCL13 may represent a novel biomarker for ovarian cancer.