Faculty Bibliography
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333
Understanding risk factors for endometrial cancer in young women
BACKGROUND:The American Cancer Society recommends physicians inform average risk women about endometrial cancer (EC) risk on reaching menopause, but new diagnoses are rising fastest in women <50 years. Educating these women about EC risks requires knowledge of risk factors. However, EC in young women is rare and challenging to study in single study populations. METHODS:We included 13,846 incident EC patients (1,639 < 50 years) and 30,569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and EC risk. We created a risk score to evaluate the combined associations and population attributable fractions of these factors. RESULTS:In younger and older women, we observed positive associations with BMI and diabetes, and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women ≥50 years (PHet<0.01). BMI was the strongest risk factor [OR≥35 vs <25 kg/m2=5.57 (95% CI:4.33-7.16) for <50 years; OR≥35 vs <25 kg/m2=4.68 (95% CI : 4.30-5.09) for ≥50 years; PHet=0.14]. Possessing ≥4 risk factors was associated with ∼9-fold increased risk in women <50 years and ∼4-fold increased risk in women ≥50 years (PHet<0.01). Together, 59.1% of ECs in women <50 and 55.6% in women ≥50 were attributable to these factors. CONCLUSIONS:Our data confirm younger and older women share common EC risk factors. Early educational efforts centered on these factors may help mitigate the rising EC burden in young women.
PMID: 39235934
ISSN: 1460-2105
CID: 5688132
The association between cumulative exposure to neighborhood walkability (NW) and diabetes risk, a prospective cohort study
PURPOSE/OBJECTIVE:To examine the association between cumulative exposure to neighborhood walkability (NW) and diabetes risk. METHODS:A total of 11,037 women free of diabetes at enrollment were included. We constructed a 4-item NW index at baseline, and a 2-item average annual NW across years of follow-up that captured both changes in neighborhood features and residential moves. We used multivariable Cox PH regression models with robust variance to estimate the hazard ratios (HRs) of diabetes by NW scores. RESULTS:Compared with women living in areas with lowest NW (Q1), those living in areas with highest NW (Q4) had 33 % (26 %-39 %) reduced risk of incident diabetes, using baseline NW, and 25 % (95 % CI 11 %-36 %), using average annual NW. Analysis using time-varying exposure showed that diabetes risks decreased by 13 % (10 %-16 %) per -standard deviation increase in NW. The associations remained similar when using inverse probability of attrition weights and/or competing risk models to account for the effect of censoring due to death or non-response. The associations of average annual NW with incident diabetes were stronger in postmenopausal women as compared to premenopausal women. CONCLUSION/CONCLUSIONS:Long-term residence in more walkable neighborhoods may be protective against diabetes in women, especially postmenopausal women.
PMID: 39442772
ISSN: 1873-2585
CID: 5738932
Cancer epidemiology biomarkers & prevention. 2024:33(9):1229-1239.DOI: 10.1158/1055-9965.EPI-24-0096
Genome-wide analysis to assess if heavy alcohol consumption modifies the association between SNPs and pancreatic cancer risk
BACKGROUND:Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. METHODS:We conducted a genome-wide interaction analysis of single nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than 3 drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies (GWAS). Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed effect meta-analyses were conducted. RESULTS:A potential novel region of association on 10p11.22, lead SNP rs7898449 (Pinteraction = 5.1 x 10-8 in the meta-analysis, Pinteraction = 2.1x10-9 in the case-control studies, Pinteraction = 0.91 cohort studies) was identified. A SNP correlated with this lead SNP is an eQTL for the NRP1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). CONCLUSIONS:We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an eQTL for the NRP1, a protein that plays an important role in the development and progression of pancreatic cancer Impact: This work can provide insight into the etiology of pancreatic cancer particularly in heavy drinkers.
PMID: 38869494
ISSN: 1538-7755
CID: 5669272
Hypertension and risk of endometrial cancer: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2)
BACKGROUND:The incidence rates of endometrial cancer (EC) are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for EC. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of EC remains unclear. In this study we evaluated hypertension as an independent risk factor for EC and whether this association is modified by other established risk factors. METHODS:We included 15,631 EC cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between hypertension and EC and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS:Hypertension was associated with an increased risk of EC (OR=1.14, 95% CI:1.09-1.19). There was significant heterogeneity by study design (Phet<0.01), with a stronger magnitude of association observed among case-control vs. cohort studies. Stronger associations were also noted for pre-/peri-menopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS:Hypertension is associated with EC risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT/CONCLUSIONS:This study provides evidence that hypertension may be an independent risk factor for EC.
PMID: 38530242
ISSN: 1538-7755
CID: 5644702
BMI and breast cancer risk around age at menopause
BACKGROUND:) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS:We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS:The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION/CONCLUSIONS:The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
PMID: 38377945
ISSN: 1877-783x
CID: 5634192
Mid-life adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and late-life subjective cognitive complaints in women
INTRODUCTION/BACKGROUND:Evidence is limited on the role of mid-life Dietary Approaches to Stop Hypertension (DASH) diet in late-life subjective cognitive complaints (SCCs). METHODS:We included 5116 women (mean age in 1985-1991: 46 years) from the New York University Women's Health Study. SCCs were assessed from 2018 to 2020 (mean age: 79 years) by a 6-item questionnaire. RESULTS:Compared to women in the bottom quartile of the DASH scores, the odds ratio (OR) for having two or more SCCs was 0.83 (95% confidence interval: 0.70-0.99) for women in the top quartile of DASH scores at baseline (P for trend = 0.019). The association was similar with multiple imputation and inverse probability weighting to account for potential selection bias. The inverse association was stronger in women without a history of cancer (P for interaction = 0.003). DISCUSSION/CONCLUSIONS:Greater adherence to the DASH diet in mid-life was associated with lower prevalence of late-life SCCs in women.
PMID: 37861080
ISSN: 1552-5279
CID: 5633712
Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
PMID: 37666943
ISSN: 1476-5551
CID: 5728432
Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
PMID: 37666943
ISSN: 1476-5551
CID: 5728422
Long-Term Exposure to Walkable Residential Neighborhoods and Risk of Obesity-Related Cancer in the New York University Women's Health Study (NYUWHS)
BACKGROUND:Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES:We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS:The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: DISCUSSION:Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.
PMID: 37791759
ISSN: 1552-9924
CID: 5635402
Cancer epidemiology biomarkers & prevention. 2023:32(9):1265-1269.DOI: 10.1158/1055-9965.EPI-23-0453
Genetic susceptibility to nonalcoholic fatty liver disease and risk for pancreatic cancer: Mendelian randomization
BACKGROUND:There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer (PC). Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for PC. METHODS:Data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium (PanScan; cases n=5090, controls n=8733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n=4,163, controls n=3,792) were analyzed. We used data on 68 genetic variants with four different MR methods (inverse variance weighting [IVW], MR-Egger, simple median, and penalized weighted median) separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and PC risk, using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for PC risk factors, including obesity and diabetes. RESULTS:No association was found between genetically predicted NAFLD and PC risk in the PanScan or PanC4 samples (e.g., PanScan, IVW OR=1.04, 95% CI: 0.88-1.22, MR-Egger OR=0.89, 95% CI: 0.65-1.21; PanC4, IVW OR=1.07, 95% CI: 0.90-1.27, MR-Egger OR=0.93, 95% CI: 0.67-1.28). None of the four MR methods indicated an association between genetically predicted NAFLD and PC risk in either sample. CONCLUSIONS:Genetic predisposition to NAFLD is not associated with PC risk. IMPACT/CONCLUSIONS:Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and PC might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and PC.
PMID: 37351909
ISSN: 1538-7755
CID: 5542972
