The association between soyfood intake and breast cancer risk is controversial. Most of the epidemiologic studies published on this topic in the 1990s were not designed to specifically address this ...question. We conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County to further investigate the role of soy. Our primary objective was to quantify breast cancer risks associated with intake of soy during adolescence and adult life among Asian-American women. During 1995–1998, we successfully interviewed 501 breast cancer patients and 594 control subjects. Intake of soy among Asian-Americans is still relatively high; the median intake was 12 mg isoflavones/day, approximately one-third of that reported in a recent study in Shanghai, China. The risk of breast cancer was significantly inversely associated with soy intake during adolescence and adult life. After adjusting for age, specific Asian ethnicity, education, migration history and menstrual and reproductive factors, women who reported soy intake at least once per week during adolescence showed a statistically significantly reduced risk of breast cancer. There was also a significant trend of decreasing risk with increasing soy intake during adult life. When we considered soy intake during both adolescence and adult life, subjects who were high-soy consumers during both time periods showed the lowest risk (OR=0.53, 95% CI=0.36–0.78) compared with those who were low consumers during both time periods. Risk of breast cancer was intermediate among subjects who were high-soy consumers during adolescence and low-soy consumers during adult life (OR=0.77, 95% CI=0.51–1.10). Based on a relatively small number of subjects, the risk did not appear to differ between those who were low consumers during adolescence and high consumers during adult life. Results remained similar after adjustment for other potential confounders including other dietary and non-dietary risk factors for breast cancer. These results show that high soy intake in childhood in Asian-Americans is associated with reduced breast cancer risk. Risk may be further reduced by intake as an adult.
Abstract Background: Prostate cancer (PCa) remains a leading cause of cancer-related death among men despite high 5-year survival rates for localized and regional diseases. This study evaluated ...healthy lifestyle and dietary patterns in relation to PCa survival in a multiethnic population. Methods: We prospectively followed 2,603 men with non-metastatic PCa in the Multiethnic Cohort (MEC) for a median duration of 10.9 years (497 African American, 754 Japanese American, 577 Latino, 129 Native Hawaiian, and 646 White men) starting in 1993. We documented 1,321 deaths, including 196 from PCa. Lifestyle pattern was assessed after diagnosis by a previously reported PCa Behavior Score, which includes BMI, physical activity, and smoking, and a modified version including diet (based on the sum of saturated fat, whole milk, alcohol, and processed meat intake). We also evaluated six indices of inflammatory and insulinemic potential of diet and lifestyle patterns (E-DII, EDIP, EDIH, ELIH, EDIR, and ELIR); and three indices of plant-based diets: an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI). We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between each index with PCa-specific and all-cause mortality. We adjusted for education, race/ethnicity, smoking, BMI, physical activity (if not part of the score), family history of PCa, and first course of treatment. Results: Across the five racial/ethnic groups, Japanese American men exhibited healthier lifestyle and dietary patterns post-diagnosis, while African American and Native Hawaiian men tended to have less healthy behaviors. The PCa Behavior Score was statistically significantly associated with a reduced risk of all-cause mortality (HR per point=0.71, 95% CI 0.63-0.80), and a similar trend persisted when incorporating diet into the score. The PDI was statistically significantly inversely associated with all-cause mortality (HR per SD=0.90, 95% CI 0.83-0.97), while the uPDI showed a positive association (HR=1.10, 95% CI 1.12-1.18). None of the lifestyle or dietary patterns were associated with PCa mortality (p-values>0.05). No clear trends were observed for inflammatory and insulinemic dietary patterns after PCa diagnosis with all-cause or PCa-specific mortality. Conclusion: Adopting a healthy lifestyle and diet was associated with longer overall survival among men with PCa. We did not find these practices to be associated with a lower risk of PCa-specific mortality among men diagnosed with non-metastatic disease. However, 85% of the observed deaths during follow-up were due to other causes; this underscores the importance of counseling all men, including those with non-metastatic prostate cancer on health behaviors to manage comorbidities. Citation Format: Anqi Wang, Erin L. Van Blarigan, Iona Cheng, June M. Chan, Peggy Wan, Song-Yi Park, Fei Chen, Loic Le Marchand, Lynne Wilkens, Stacey A. Kenfield, Christopher A. Haiman. Associations between post-diagnostic lifestyle and dietary patterns with prostate cancer survival in the Multiethnic Cohort abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2220.
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.
Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(-8) Most studies have been ...conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10(-6)) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 95% confidence interval (CI): 1.47-2.36); P = 2.5×10(-7), 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21-1.55); P = 4.0×10(-7)), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36-2.01); P = 4.1×10(-7)) and 16q12.2 rs142319636; OR = 1.69 (95% CI: 1.37-2.08); P=7.8×10(-7). Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10(-5)) and 11q12.2 (P = 6.8×10(-5)), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations.
Abstract
The greater incidence of prostate cancer in men of African ancestry remains one of the most important unanswered health disparities globally. No established environmental/lifestyle risk ...factors have been identified, with the only established risk factors being age, race/ethnicity and family history, all of which implicate genetic susceptibility. GWAS have clearly validated the importance of genetic susceptibility in prostate cancer, with ~100 common risk loci identified to date which in aggregate explain 33% of the familial risk. Genetic studies in African ancestry populations have provided strong evidence for genetic factors in contributing to the greater incidence of prostate cancer in men of African ancestry. To further explore this hypothesis, we conducted a genome-wide association study (GWAS) of prostate cancer among Ugandan men. Specifically, we genotyped the Illumina OncoArray, which includes a 260K GWAS backbone, in 560 prostate cancer cases (119 with Gleason score ≥8) and 480 controls and tested the associations of 448,939 genotyped and 16,396,662 imputed variants with >1% frequency. The most statistically significant variants were observed at the 8q24 risk locus (rs72725854, OR=3.37, P=2.14x10-13). We also observed suggestive signals with 106 variants outside of known risk regions with p-values <10-5 and >10-7. Of the 104 known risk variants, 100 are polymorphic in Uganda men, of which, 66 (66%) had effects that were directionally consistent in their association with prostate cancer risk as previously reported and 8 (8%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs16901979 at 8q24 (OR=1.45, p=0.0001) and rs1512268 at 8p21.2 (OR=1.31, p=0.0087). In addition to these findings, we will also present the results from replication testing of the most significant associations from the GWAS in the Ghana Prostate GWAS Study and the African Ancestry Prostate Cancer Consortium, as well as provide a detailed comparison of polygenic risk models of the known prostate cancer variants between these two African populations, African Africans and men of European ancestry.
Citation Format: Zhaohui Du, Alexander Lubmawa, Susan Gundell, Peggy Wan, Nalukenge Cissy, Muwanga Proscovia, Lutalo Moses, Nansereko Deborah, Ndaruhutse Olivia, Katuku Molly, Lubwama Alexander, Rosemary Nassanga, Benson Masaba, Sam Kaggwa, Dan Namuguzi, Vicky Kiddu, Asiimwe Luke, Kuteesa J, Dabanja M. Henry, David Conti, Christopher A. Haiman, Stephen Watya. A genome-wide association study of prostate cancer in Uganda abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1305. doi:10.1158/1538-7445.AM2017-1305
Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, ...BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%-66% of PRS), men with low (0%-33%) and high (66%-100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 95% confidence interval (CI) = 0.58-7.49 and 18.06 (95% CI = 4.24-76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46-0.71) and 3.02 (95% CI = 2.53-3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24-30.54) and 28.99 (95% CI = 4.39-191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31-0.95) and 3.22 (95% CI = 2.20-4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status.
These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.
Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, ...gene panels are also likely to be incomplete and missing genes that influence PCa risk and aggressive disease.
To identify genes associated with aggressive PCa.
A 2-stage exome sequencing case-only genetic association study was conducted including men of European ancestry from 18 international studies. Data analysis was performed from January 2021 to March 2023. Participants were 9185 men with aggressive PCa (including 6033 who died of PCa and 2397 with confirmed metastasis) and 8361 men with nonaggressive PCa.
Sequencing data were evaluated exome-wide and in a focused investigation of 29 DNA repair pathway and cancer susceptibility genes, many of which are included on gene panels.
The primary study outcomes were aggressive (category T4 or both T3 and Gleason score ≥8 tumors, metastatic PCa, or PCa death) vs nonaggressive PCa (category T1 or T2 and Gleason score ≤6 tumors without known recurrence), and metastatic vs nonaggressive PCa.
A total of 17 546 men of European ancestry were included in the analyses; mean (SD) age at diagnosis was 65.1 (9.2) years in patients with aggressive PCa and 63.7 (8.0) years in those with nonaggressive disease. The strongest evidence of association with aggressive or metastatic PCa was noted for rare deleterious variants in known PCa risk genes BRCA2 and ATM (P ≤ 1.9 × 10-6), followed by NBN (P = 1.7 × 10-4). This study found nominal evidence (P < .05) of association with rare deleterious variants in MSH2, XRCC2, and MRE11A. Five other genes had evidence of greater risk (OR≥2) but carrier frequency differences between aggressive and nonaggressive PCa were not statistically significant: TP53, RAD51D, BARD1, GEN1, and SLX4. Deleterious variants in these 11 candidate genes were carried by 2.3% of patients with nonaggressive, 5.6% with aggressive, and 7.0% with metastatic PCa.
The findings of this study provide further support for DNA repair and cancer susceptibility genes to better inform disease management in men with PCa and for extending testing to men with nonaggressive disease, as men carrying deleterious alleles in these genes are likely to develop more advanced disease.
Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women ...of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (
p
< 0.05) in stage 2, which reached statistical significance levels of 10
−6
and 10
−5
in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18,
p
= 4.3 × 10
−6
; rs10510333 at chromosome 3p26: OR = 1.15,
p
= 1.5 × 10
−5
). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.
Abstract
Previous studies have provided suggestive evidence of an inverse association between atopic allergic conditions (AAC) and colorectal cancer (CRC) incidence and mortality in predominantly ...White populations. Here we examined the association between AAC and CRC among White, African American, Native Hawaiian, Japanese American, and Latino men and women in the Multiethnic Cohort (MEC). AAC exposure status was ascertained via self-reported physician diagnosis using a baseline 26-page validated questionnaire. The analysis included 4259 incident CRC cases and 1221 CRC-related deaths ascertained between 1993 and 2010. We also examined associations by ethnic group, location, and stage of cancer as well as potential effect modification by CRC risk factors. AAC was associated with a reduced risk of colorectal cancer incidence among both men and women (RR = 0.85, 95% CI 0.79, 0.91, p < 0.0001). The reduction in risk was noted in each population and was significant in Whites (RR = 0.84, 95% CI 0.71, 0.98, p = 0.03), African Americans (RR = 0.81, 95% CI 0.69, 0.95, p = 0.01), and Japanese Americans (RR = 0.85, 95% CI 0.75, 0.97, p = 0.01). Suggestive evidence of effect modification was noted by smoking (p = 0.07) and aspirin use (p = 0.08), with a greater protective effect observed among current smokers (RR = 0.72, 95% CI 0.58, 0.89, p = 0.002) and never users of aspirin (RR = 0.81, 95% CI 0.73, 0.89, p < 0.0001). Individuals with AAC also had a 19% reduction in CRC-related mortality (P = 0.004). Colonoscopy screening is unlikely to explain these inverse associations, as individuals with AAC were more likely to be screened than those without AAC (p < 0.003 for all ethnic groups). These findings provide support for an association between immune pathology and colorectal cancer, potentially through modulation of the immune system's IgE-mediated pathways systemically and within the gut.
Citation Format: Neal A. Tambe, Dan O. Stram, Lynne R. Wilkens, Peggy Wan, Frank D. Gilliland, Brian E. Henderson, Loic Le Marchand, Christopher A. Haiman. Atopic allergic conditions and colorectal cancer risk in 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-261. doi:10.1158/1538-7445.AM2014-LB-261
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