Abstract only
Background
Given the increasing number of colorectal cancer (CRC) survivors, the possible effect of modifiable health behaviors, in particular optimal nutrition, on prognosis is ...critical. In recent years, the idea has emerged that dietary patterns may be better suited to capture the complexity of dietary intake than the analysis of single foods or nutrients. We investigated the association between four
a priori
dietary quality indexes assessed 6.0±4.7 years before diagnosis and CRC‐specific survival in the Multiethnic Cohort (MEC).
Methods
At baseline, more than 215,000 African American, Native Hawaiian, Japanese American, Latino, and white adults completed a validated quantitative food frequency questionnaire designed to capture dietary intake in the five relevant ethnic groups. Colorectal cancer cases and deaths from all causes were identified through linkages to SEER cancer registries and the National Death Index. Cox proportional hazards regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the Healthy Eating Index‐2010 (HEI‐2010), the Alternative HEI‐2010 (AHEI‐2010), the Alternate Mediterranean Diet Score (aMED), and the Dietary Approaches to Stop Hypertension (DASH) while adjusting for relevant confounders.
Results
Among 4,204 MEC participants diagnosed with invasive CRC cases during follow‐up, 1,976 all‐cause and 1,095 CRC‐specific deaths were identified. CRC‐specific survival was significantly associated with higher scores on the HEI‐2010 (p
trend
=0.04); for one standard deviation increase in the HEI‐2010, the HR was 0.93 (95%CI: 0.88–0.99). Individuals in the highest vs. lowest diet quality quartile experienced 20% lower mortality (HR=0.80; 95%CI: 0.67–0.97). A higher aMED score was associated with borderline lower CRC mortality (HR=0.94; 95%CI: 0.88–1.01; p
trend
=0.09). No significant associations of CRC‐specific survival with the DASH and AHEI‐2010 indexes were detected.
Conclusions
The current findings may be related to the HEI‐2010 inclusion of dairy intake as a positive dietary component and added sugars from all sources as a negative one. Also, scores for the HEI‐2010 and aMED are positively influenced by fish intake and a higher ratio of unsaturated to saturated fatty acids, which are considered possible preventive factors. These results emphasize the merit of an overall healthful diet for optimal survival outcomes.
Support or Funding Information
The Multiethnic Cohort Study has been supported by grants R37CA54281 and UM1CA164973 from the National Cancer Institute. Dr. Harmon was supported by postdoctoral fellowships on grant R25CA90956. The tumor registries are supported by NCI contracts N01 PC 35137 and N01 PC 35139.
Epidemiologic studies have demonstrated a tendency for common cancers to aggregate in families. The authors investigated the effects of family history of cancer at multiple sites, including the ...breast, ovary, colorectum, and prostate, on ovarian cancer risk among 607 controls and 558 ovarian cases in Hawaii and Los Angeles, California, in 1993–1999. A family history of cancer of the breast, ovary, colorectum, or prostate in first-degree relatives was associated with an increased risk of ovarian cancer (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.1, 2.6; OR = 3.2, 95% CI: 1.3, 7.9; OR = 1.5, 95% CI: 0.9, 2.5; and OR = 1.6, 95% CI: 1.0, 2.8, respectively). A greater risk of ovarian cancer was observed for women with parents rather than siblings with a history of breast or prostate cancer and for women with parental colorectal cancer diagnosed at an early age, suggesting a genetic predisposition among these women. The risk of nonmucinous tumors, but not mucinous tumors, was positively associated with a family history of cancer. No significant interaction effects on risk existed between oral contraceptive pill use or pregnancy and family history of breast and/or ovarian cancer. Study findings suggest that ovarian cancer aggregates with several common cancers in family members.
Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC ...risk in Asian women.
Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.
At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio OR = 1.34, P = 8.7 × 10−9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10−9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10−8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10−7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10−7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10−7).
While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.
•This study analyzed genotyping data from >7,000 individuals of Asian descent to find risk loci for epithelial ovarian cancer•We identified two novel genome-wide significant loci, plus evidence of association at an additional 28 regions•eQTL analyses in 404 TCGA tumors highlight ESPNL as a novel susceptibility gene for ovarian cancer
We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, ...between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.
Abstract
Purpose: A polygenic risk score (PRS) has demonstrated great potential in stratifying breast cancer risk in non-African ancestry populations. Several modifiable lifestyle risk factors have ...been identified for breast cancer, although little is known regarding their effects among women with varying genetic risk. Methods: In the Multiethnic Cohort (MEC), we conducted a nested case-control study of 3,229 breast cancer cases and 3,921 controls from five major racial/ethnic groups (White, African American, Latino, Japanese American, and Native Hawaiian). We examined a PRS of 313 variants in association with breast cancer risk and evaluated the interaction with selected modifiable lifestyle factors on the risk of breast cancer. The modifiable lifestyle factors examined included body mass index (BMI), physical activity, smoking, alcohol consumption, and five diet quality indexes, such as the Healthy Eating Index (HEI)-2010, the Alternative Healthy Eating Index (AHEI)-2010, the alternate Mediterranean Diet score (aMED), the Dietary Approaches to Stop Hypertension score (DASH), and the Dietary Inflammatory Index (DII). Results: The 313-variant PRS was strongly associated with breast cancer risk across the five racial/ethnic groups, with per standard deviation (SD) odds ratios (OR) of 2.07 (95% CI=1.63-2.63) in Native Hawaiian, 1.72 (95% CI=1.54-1.92) in White, 1.56 (95% CI=1.36-1.77) in Latina, 1.45 (95% CI=1.31-1.60) in Japanese American, and 1.32 (95% CI=1.20-1.44) in African American women. For the lifestyle factors, BMI (OR=0.84, 95% CI=0.75-0.93, for <25 vs. ≥ 25 kg/m2) and alcohol consumption (OR=1.14, 95% CI=1.02-1.26 for drinkers vs. non-drinkers) were significantly associated with breast cancer risk. We also observed a suggestive positive association for smoking (OR=1.14, 95% CI=0.98-1.32 for current vs. never/past smokers) and a suggestive inverse association for AHEI-2010 (OR=0.96, 95%CI=0.91-1.01 per SD increment). No association was observed for physical activity or other dietary indexes. We found that the association of BMI and AHEI-2010 with breast cancer risk depended on PRS. Specifically, among women with above-average genetic risk (50-100% of PRS), the OR of breast cancer was 0.77 (95% CI=0.66-0.88) for women with a BMI <25 kg/m2 (vs. BMI³25 kg/m2), while among women with below-average genetic risk (0-50% of PRS) the OR was 0.96 (95%CI=0.81-1.14, P-heterogeneity=0.04). In contrast, a significant inverse association of AHEI-2010 (per SD) with breast cancer risk was only observed in women with below-average genetic risk (OR=0.90, 95%=0.83-0.97) but not among women with above-average genetic risk (OR=1.00, 95%CI=0.94-1.08, P-heterogeneity=0.04). Conclusions: In line with previous reports, the 313-variant PRS was effective in stratifying breast cancer risk, with diminished transferability for women of African ancestry. Our findings also suggest that maintaining a healthy BMI may offset the genetic risk of breast cancer, while adhering to a healthy dietary pattern may further reduce risk for women with lower genetic risk.
Citation Format: Alisha Chou, Fei Chen, Peggy Wan, Xin Sheng, Song-Yi Park, Daniel O. Stram, Lynne R. Wilkens, Loic Le Marchand, Christopher A. Haiman. Interactions of a polygenic risk score and modifiable lifestyle factors for breast cancer in the Multiethnic Cohort abstract. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C102.
Abstract
Background: Coffee consumption has been suggested to reduce hepatocellular carcinoma (HCC) risk in epidemiological studies. Yet, data from prospective studies in US populations are ...nonexistent. Here we evaluated the association between coffee intake and HCC incidence in multiethnic US populations.
Methods: We conducted a prospective analysis of 179,890 African-American, Native Hawaiian, Japanese-American, Latino and white men and women who were recruited into the Multiethnic Cohort Study between 1993 and 1996. Participants reported their coffee consumption and other dietary and lifestyle factors at baseline and were followed up to 18 years for HCC incidence. Serologic testing for hepatitis B (HBV) and C (HCV) infection was performed on a subset of cohort participants (152 HCC cases and 460 non-cases). Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusting for sex, ethnicity, education, alcohol intake, smoking status, body mass index (BMI), and history of diabetes mellitus.
Results: During a median follow-up period of 16.6 years, 498 participants had developed HCC. High levels of regular coffee consumption were associated with reduced risk of HCC (P for trend <0.0001). Compared to non-drinkers/low consumers (up to six cups per week) of coffee, individuals who consumed one to three cups of coffee per day had a 29% reduction in risk of HCC (RR=0.71; 95% CI: 0.60, 0.86) and those who had four or more cups of coffee per day had a 42% reduction in risk of HCC (RR=0.58; 95% CI: 0.36, 0.92). The inverse relationships between coffee and HCC were similar regardless of the participants’ ethnicity, sex, BMI, smoking status, alcohol intake, or diabetes status. Within a subset of cohort participants with available HBV and HCV serologic data, coffee consumption was not associated with infection status (P=0.63).
Conclusions: These results suggest that an increased coffee consumption may reduce the risk of developing HCC in multiethnic US populations.
Citation Format: Veronica Wendy Setiawan, Lynne R. Wilkens, Brenda Y. Hernandez, Loic Le Marchand, Brian E. Henderson. Coffee intake reduces hepatocellular carcinoma risk: The Multiethnic Cohort. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-281. doi:10.1158/1538-7445.AM2014-LB-281
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