Dale P Sandler

Occupational exposures among hairdressers and the occurrence of hormone-related conditions

Objective To investigate the association between hairdresser exposures and hormone-related conditions. Methods Using data from 50 800 eligible Sister Study participants (enrolled 2003–2009, aged 35–74 years), we estimated ORs and 95% CIs for associations between ever working as a hairdresser (n=1803) and prevalent fibroids, endometriosis, hysterectomy and oophorectomy. We estimated HRs and 95% CI for incident fibroids, endometriosis, breast, uterine and ovarian cancers among ever hairdressers versus never hairdressers. We also examined associations of hormone-related diseases and professional use of products such as bleach, perms, chemical straighteners, permanent hair colour, hairspray, barbicide, formaldehyde and alcohol, comparing data from 985 long-term hairdressers who worked ≥2 years to non-long-term hairdressers (never workers and those working <2 years). Results Ever-hairdressers were more likely than never-hairdressers to have had a prebaseline hysterectomy (OR=1.23: 95% CI 1.11 to 1.36). Hysterectomies were more common among long-term hairdressers with more frequent applications of perms, chemical straighteners and permanent hair colour compared with less frequent applicators or never hairdressers. Ever-hairdressers had higher rates of incident endometriosis (477 cases, HR=1.61: 95% CI 1.08 to 2.38) compared with never-hairdressers, but there were no notable associations between working as a hairdresser and fibroids (1805 cases, HR=1.04: 95% CI 0.80 to 1.34), breast cancer (4628 cases, HR=0.98: 95% CI 0.83 to 1.16), ovarian cancer (300 cases, HR=1.33: 95% CI 0.77 to 2.29) or uterine cancer (447 cases, HR=1.04: 95% CI 0.60 to 1.77). In race-stratified analyses, Black hairdressers were more likely to be diagnosed with fibroids than Black never-hairdressers (201 cases, HR=1.56: 95% CI 0.93 to 2.62). Conclusions Hairdresser occupation was associated with increased odds of hysterectomy and increased rates of incident endometriosis and possibly fibroids among Black women.

The independent and joint associations of hysterectomy and uterine fibroids or endometriosis with ovarian cancer incidence: results from a US-based cohort

Abstract Uterine fibroids and endometriosis may be associated with an increased risk of ovarian cancer. Less is known about the role of hysterectomy in these associations. We estimated the independent and joint associations of hysterectomy, fibroids, and endometriosis with ovarian cancer incidence in the prospective Sister Study cohort (2003-2009). We used time-varying Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). By the end of follow-up, 34% of 40 928 eligible participants had fibroids, 13% had endometriosis, and 7% had both. A total of 274 women developed ovarian cancer during follow-up (median = 12.3 years). In mutually adjusted models, fibroids (HR, 1.65; 95% CI, 1.28-2.12) and possibly endometriosis (HR, 1.16; 95% CI, 0.82-1.63) were positively associated with ovarian cancer. Hysterectomies (20% of participants) were also positively associated with ovarian cancer (HR, 1.29; 95% CI, 0.95-1.74). There was some evidence that hysterectomies may mitigate ovarian cancer risk among women with fibroids (HR, 0.83; 95% CI, 0.56-1.24) but not among women with endometriosis (HR, 1.20; 95% CI, 0.65-2.22). Identifying these joint associations adds to our understanding of ovarian cancer etiology and may help inform decisions about how women with fibroids, endometriosis, and hysterectomies are treated and surveilled for ovarian cancer. This article is part of a Special Collection on Gynecological Cancer.

Pubertal Timing and Incident Ovarian Cancer in the Sister Study Cohort

Abstract Background: Pubertal milestones such as menarche (first period) and thelarche (onset of breast development) are markers of hormonal changes that may be relevant to the hormonal etiology of ovarian cancer. Prior studies of the association between age at menarche and ovarian cancer risk have been inconsistent, whereas age at thelarche has not been examined in relation to ovarian cancer incidence. Methods: With data from 40,809 women in the Sister Study, we used multivariable-adjusted Cox proportional hazards regression to estimate HRs and 95% confidence intervals (CI) for associations of self-reported ages at thelarche and menarche with incident ovarian cancer, both overall and by histotype. Results: During a median follow-up of 13.3 years, 291 women reported a diagnosis of ovarian cancer. Ages at thelarche (HR = 0.94; 95% CI, 0.87–1.02 per 1-year older) and menarche (HR = 0.99; 95% CI, 0.91–1.07 per 1-year older) were not associated with ovarian cancer overall. Although imprecise, HRs suggested a possible inverse association of ages at thelarche (HR = 0.71; 95% CI, 0.48–1.04) and menarche (HR = 0.79; 95% CI, 0.59–1.04) with the incidence of clear-cell tumors. Conclusions: Ages at thelarche and menarche were not associated with ovarian cancer incidence overall. Impact: Though our results do not provide clear evidence of associations of pubertal timing with ovarian cancer incidence, possible associations of earlier thelarche and menarche with increased incidence of ovarian clear-cell carcinoma may warrant further investigation, especially considering secular trends toward earlier thelarche.

The human oral microbiome and risk of colorectal cancer within three prospective cohort studies in the United States

AbstractBackgroundOral microbes detected in feces have been associated with colorectal cancer (CRC) in cross‐sectional studies. This study investigated the prospective associations between the oral microbiome and incident CRC in the Agricultural Health Study (AHS), National Institutes of Health–AARP (NIH‐AARP) Diet and Health Study, and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.MethodsIndividuals with oral samples collected before incident CRC diagnoses were identified in the AHS (N = 331), NIH‐AARP (N = 249), and PLCO (N = 446) and compared with referent subcohorts (N = 3431). The V4 region of the 16S ribosomal RNA gene was sequenced from oral wash DNA, and the data were processed with QIIME2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and by anatomic subsite (i.e., proximal colon, distal colon, and rectum) were estimated with Cox proportional hazards models with adjustment for potential confounders by cohort and then meta‐analyzed.ResultsOverall, no associations were found between microbial characteristics and CRC risk. However, associations were observed with alpha and beta diversity indices and individual genera in analyses stratified by anatomic subsite. For instance, the presence of Olsenella was strongly positively associated with distal colon cancer risk (HR, 2.16; 95% CI, 1.59–2.95), whereas the presence of Prevotella 2 was positively associated with rectal cancer risk (HR, 1.68; 95% CI, 1.14–2.46).ConclusionsThis large study of the prospective association between the oral microbiome and CRC risk showed numerous site‐specific associations, including multiple associations with distal colon and rectal cancer risk.

Intimate Care Products and Incidence of Hormone-Related Cancers: A Quantitative Bias Analysis

PURPOSE Intimate care products may contain substances associated with increased risk of hormone-related cancers. The relationship between genital talc use and ovarian cancer, in particular, has been well studied, but concerns about recall bias and exposure misclassification have precluded conclusions. We examined the association between intimate care products and female hormone–related cancers, accounting for potential biases, using data from a US-based cohort study. METHODS The Sister Study enrolled 50,884 women who had a sister with breast cancer. Data on genital talc use and douching were collected at enrollment (2003-2009) and follow-up (2017-2019). We used Cox proportional hazards models to estimate hazard ratios (HRs) for associations between intimate care product use and breast, ovarian, and uterine cancers. To account for potential exposure misclassification and recall bias, we conducted quantitative bias analyses under various exposure reassignment assumptions. RESULTS Across considered scenarios, 41%-64% of participants douched and 35%-56% used genital talc. In models adjusted for exposure misclassification, genital talc use was positively associated with ovarian cancer (HR range, 1.17-3.34) Frequent douching and douching during young adulthood were positively associated with ovarian cancer, but neither douching nor talc was associated with breast or uterine cancer. Differential reporting of talc use by cases and noncases likely produces positive biases, but correcting for error still resulted in HRs above 1.0. For example, HR, 1.40 (95% CI, 1.04 to 1.89) when 25% of exposed cases and 10% of unexposed noncases had talc status reassigned. CONCLUSION Although results show how differential recall would upwardly bias estimates, corrected results support a positive association between use of intimate care products, including genital talc, and ovarian cancer.

Hair Straightener Use in Relation to Prevalent and Incident Fibroids in the Sister Study with a Focus on Black Women

Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners ("straighteners") may contribute to fibroid development. We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes. Data from 4,162 Black women in the Sister Study, a prospective cohort of women 35-74 y of age (enrolled 2003-2009), were analyzed. We used logistic regression to estimate odds ratios (ORs) for the association of straightener use at 10-13 y of age and self-reported young-onset fibroids. We used Cox regression to assess hazard ratios (HRs) for straightener use (age 10-13 y and in 12 months before enrollment) and incident fibroids among 779 premenopausal Black women. Similar analyses were conducted in 40,782 non-Hispanic White women. Over 70% of Black women used straighteners. In comparison with no use, any [ Hair straightener use may be positively associated with fibroid risk. https://doi.org/10.1289/EHP14493.

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium

Abstract Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. Results: Most associations did not vary by tumor site (Phet ≥ 0.05). Associations between first pregnancy (Phet = 0.04), tubal ligation (Phet = 0.01), and early-adult (age 18–21 years) body mass index (BMI; Phet = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (Phet = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Abstract Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60–2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10–1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04–1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09–1.17)], endometrioid [1.20 (1.10–1.32)], and clear cell [1.37 (1.18–1.58)], but not mucinous [0.99 (0.88–1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies. Significance: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.

Reproductive and Hormonal Factors and Risk of Ovarian Cancer by Tumor Dominance: Results from the Ovarian Cancer Cohort Consortium (OC3)

Abstract Background: Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells. Methods: We pooled data from 9 prospective studies participating in the Ovarian Cancer Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance. Results: Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer (Pheterogeneity = 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors (Pheterogeneity = 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors (Pheterogeneity = 0.08). Conclusions: These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin. Impact: Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.

Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia

PURPOSE Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors. METHODS Nine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2). RESULTS Overall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design ( P = .48) or histotype ( P = .60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all P-heterogeneity > .05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90). CONCLUSION This study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.

Cohort Profile: The Ovarian Cancer Cohort Consortium (OC3)

Use of personal care product mixtures and incident hormone-sensitive cancers in the Sister Study: A U.S.-wide prospective cohort

Personal care products (PCPs), a source of endocrine-disrupting chemical exposure, may be associated with the risk of hormone-sensitive cancers. Few studies have investigated associations for PCP use with the incidence of hormone-sensitive cancers or considered the joint effect of multiple correlated PCPs. We examined associations between frequently used, or "everyday", PCPs and incident cancers of the breast, ovary, and uterus with a fucus on the joint effect of multiple product exposure. Sister Study participants (n=49 899) self-reported frequency of use in the year before enrollment (2003-2009) for 41 PCPs. Using five-level frequency categories based on questionnaire options, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the associations between multiple PCP use and incident breast, ovarian, and uterine cancer using quantile-based g-computation with Cox proportional hazards regression as the underlying model. Multiple PCP use was examined using groupings (beauty, hygiene, and skincare products) determined by both a priori knowledge and Spearman correlation coefficients for co-occurring product use. Associations between individual PCPs and the three cancers were also examined using Cox proportional hazards models coupling with Benjamini-Hochberg procedure for multiple comparisons. Over an average of 11.6 years, 4 226 breast, 277 ovarian, and 403 uterine cancer cases were identified. Positive associations were observed between the hygiene mixture and ovarian cancer (HR=1.35, 95%CI=1.00, 1.83) and the beauty mixture with postmenopausal breast cancer (HR=1.08, 95%CI=1.01, 1.16). Additionally, we observed an inverse association between the skincare mixture and breast cancer (HR=0.91, 95%CI=0.83, 0.99). No significant associations were observed for individual products after corrected for multiple comparison. Findings from this multi-product, joint-effect approach contribute to the growing body of evidence for associations between PCPs and breast cancer and provides novel information on ovarian and uterine cancer.