Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study.

BACKGROUND: The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial, and there is a need to investigate the heterogeneity of effects among racial and ethnic groups. OBJECTIVES: To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS: We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 y. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS: As of December 2017, 4403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4, and Q5 compared with Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (95% CI: 0.96, 1.16), 1.12 (95% CI: 1.01, 1.24), and 1.13 (95% CI: 1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 y at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among racial and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSIONS: In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC, and the association was strongest for colon cancer, younger participants, and Latinos.

The EAT-Lancet Diet Index is Associated with Lower Obesity and Incidence of Type 2 Diabetes in the Multiethnic Cohort.

BACKGROUND: The EAT-Lancet Commission has developed dietary recommendations, named EAT-Lancet diet, to promote healthy nutrition and sustainable food production worldwide. OBJECTIVE: We developed an adapted score for the EAT-Lancet diet for participants of the Multiethnic Cohort (MEC) Study and its relation with incidence of obesity and type 2 diabetes (T2D). METHODS: The MEC includes 5 ethnic groups followed since 1993-96. Anthropometric characteristics and dietary intake were assessed by questionnaire at cohort entry (Qx1) and 10 y later (Qx3). To create the EAT-Lancet Index (range: 0-48 points), a 3-point scoring system for 16 food groups standardized to 2,500 kcal/d was applied. T2D cases were identified through repeated self-reports and administrative data. In a prospective design, obesity at Qx3 and T2D incidence were evaluated using Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (95%CI) while adjusting for relevant covariates. RESULTS: Among 193,379 MEC participants, the overall mean EAT-Lancet Index score was 25±4 points and 46,140 new T2D cases were identified. Higher adjusted means were observed in women than men, in participants of Japanese American and Native Hawaiian ancestry, and in those with healthy weight than overweight or obesity. Obesity was lower in cohort members with higher EAT-Lancet scores (HR 0.76; 95%CI 0.73, 0.79 for tertiles 3 vs. 1). Although T2D incidence was 10% lower among participants in the highest (27-42 points) vs. lowest (9-23 points) EAT-Lancet Index tertile (HR 0.90; 95%CI 0.88, 0.92), the association was attenuated after BMI adjustment (HR 0.97; 95%CI 0.94, 0.99). This inverse association with T2D was restricted to African American and European American participants. CONCLUSIONS: These findings support the hypothesis that adherence to the EAT-Lancet diet is related to a lower risk for obesity, which may be partially responsible for the small reduction in T2D incidence.

Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations.

BACKGROUND: Germline mutations of breast cancer susceptibility gene BRCA1 and BRCA2 (gBRCA1/2) are associated with elevated risk of breast cancer in young women in Asia. BRCA1 and BRCA2 proteins contribute to genomic stability through homologous recombination (HR)-mediated double-strand DNA break repair in cooperation with other HR-related proteins. In this study, we analyzed the targeted sequencing data of Korean breast cancer patients with gBRCA1/2 mutations to investigate the alterations in HR-related genes and their clinical implications. MATERIALS AND METHODS: Data of the breast cancer patients with pathogenic gBRCA1/2 mutations and qualified targeted next-generation sequencing, SNUH FiRST cancer panel, were analyzed. Single nucleotide polymorphisms, small insertions, and deletions were analyzed with functional annotations using ANNOVAR. HR-related genes were defined as ABL1, ATM, ATR, BARD1, BRCA1, BRCA2, CDKN1A, CDKN2A, CHEK1, CHEK2, FANCA, FANCD2, FANCG, FANCI, FANCL, KDR, MUTYH, PALB2, POLE, POLQ, RAD50, RAD51, RAD51D, RAD54L, and TP53. Mismatch-repair genes were MLH1, MSH2, and MSH6. Clinical data were analyzed with cox proportional hazard models and survival analyses. RESULTS: Fifty-five Korean breast cancer patients with known gBRCA1/2 mutations and qualified targeted NGS data were analyzed. Ethnically distinct mutations in gBRCA1/2 genes were noted, with higher frequencies of Val1833Ser (14.8%), Glu1210Arg (11.1%), and Tyr130Ter (11.1%) in gBRCA1 and Arg2494Ter (25.0%) and Lys467Ter (14.3%) in gBRCA2. Considering subtypes, gBRCA1 mutations were associated with triple-negative breast cancers (TNBC), while gBRCA2 mutations were more likely hormone receptor-positive breast cancers. At least one missense mutation of HR-related genes was observed in 44 cases (80.0%). The most frequently co-mutated gene was TP53 (38.1%). In patients with gBRCA1/2 mutations, however, genetic variations of TP53 occurred in locations different from the known hotspots of those with sporadic breast cancers. The patients with both gBRCA1/2 and TP53 mutations were more likely to have TNBC, high Ki-67 values, and increased genetic mutations, especially of HR-related genes. Survival benefit was observed in the TP53 mutants of patients with gBRCA2 mutations, compared to those with TP53 wild types. CONCLUSION: Our study showed genetic heterogeneity of breast cancer patients with gBRCA1 and gBRCA2 mutations in the Korean populations. Further studies on precision medicine are needed for tailored treatments of patients with genetic diversity among different ethnic groups.

Avocado and Guacamole Consumption and Colorectal Cancer Risk: The Multiethnic Cohort Study.

Dietary fiber and phytonutrients can protect against colorectal cancer, yet their consumption is low in the US. Avocados are a potential source of these beneficial nutrients. Therefore, this study aimed to examine the relationship between avocados/guacamole consumption and colorectal cancer risk in the Multiethnic Cohort Study. We assessed avocados/guacamole consumption by using a food frequency questionnaire. We classified participants into three consumer groups: <1 serving/month, 1-3 servings/month, and ≥1 serving/week with one serving defined as ½ avocado or ½ cup. Colorectal cancer cases were ascertained through the Surveillance, Epidemiology and End Results Program cancer registries. Cox proportional hazards models of colorectal cancer were used to calculate hazard ratios and 95% confidence intervals across avocados/guacamole intake groups in each sex overall and by anatomic subsite (i.e., right colon, left colon, and rectum) and race and ethnicity. Of 192,651 eligible participants, 62.8% reported consuming <1 serving/month avocados/guacamole, 26.7% reported 1-3 servings/month, and 10.5% reported ≥1 serving/week. When adjusted for relevant covariates, there was no significant association with incident colorectal cancer overall, for subsites, or within racial and ethnic subgroups (all p for trend ≥ 0.06). In this large prospective cohort study, we did not find that consumption of avocados/guacamole was associated with colorectal cancer risk.

Differences in Neuropathology between Nitroglycerin-Induced Mouse Models of Episodic and Chronic Migraine.

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed. Mechanical thresholds were similar. Notable neuropathological distinctions were observed in Sp5C and ACC. ACC showed increased c-Fos and NeuN expression in CM (p < 0.001) and unchanged in EM. Sp5C had higher c-Fos and NeuN expression in EM (p < 0.001). Iba1 was upregulated in Sp5C of EM and ACC of CM (p < 0.001). Proinflammatory markers were strongly expressed in Sp5C of EM and ACC of CM. CGRP expression was elevated in both regions and was higher in CM. VIP exhibited higher levels in the Sp5C of EM and ACC of CM, whereas PACAP and substance P were expressed in the Sp5C in both models. Despite similar thresholds, distinctive neuropathological differences in Sp5C and ACC between EM and CM models suggest a role in the EM to CM transformation.

Smoking and pancreatic cancer: a sex-specific analysis in the Multiethnic Cohort study.

PURPOSE: To examine whether the detrimental smoking-related association with pancreatic cancer (PC) is the same for women as for men. METHODS: We analyzed data from 192,035 participants aged 45-75 years, enrolled in the Multiethnic Cohort study (MEC) in 1993-1996. We identified PC cases via linkage to the Hawaii and California Surveillance, Epidemiology, and End Results Program cancer registries through December 2017. RESULTS: During a mean follow-up of 19.2 years, we identified 1,936 incident PC cases. Women smokers smoked on average less than men smokers. In multivariate Cox regression models, as compared with sex-specific never smokers, current smokers had a similar elevated risk of PC for women, hazard ratio (HR) 1.49 (95% CI 1.24, 1.79) and as for men, HR 1.48 (95% CI 1.22, 1.79) (pheterogeneity: 0.79). Former smokers showed a decrease in risk of PC for men within 5 years, HR 0.74 (95% CI 0.57, 0.97) and for women within 10 years after quitting, HR 0.70 (95% CI 0.50, 0.96), compared with their sex-specific current smokers. Both sexes showed a consistent, strong, positive dose-response association with PC for the four measures (age at initiation, duration, number of cigarettes per day, number of pack-years) of smoking exposure among current smokers and an inverse association for years of quitting and age at smoking cessation among former smokers (all ptrend's < 0.001). CONCLUSION: Although MEC women smoke on average less than their men counterparts, the smoking-related increase in PC risk and the benefits of cessation seem to be of similar magnitudes for women as for men.

Change in the inflammatory potential of diet over 10 years and subsequent mortality: the Multiethnic Cohort Study.

Dietary inflammatory potential assessed by the Dietary Inflammatory Index (DII®) has been associated with health outcomes. However, longitudinal changes in the DII in relation to health outcomes rarely have been studied. This study aimed to examine change in the DII score over 10 years and its association with subsequent mortality in the Multiethnic Cohort. The analysis included 56 263 African American, Japanese American, Latino, Native Hawaiian and White participants who completed baseline (45-75 years) and 10-year follow-up surveys, including a FFQ. Mean energy-adjusted DII (E-DII) decreased over 10 years in men (from -0·85 to -1·61) and women (from -1·80 to -2·47), reflecting changes towards a more anti-inflammatory diet. During an average follow-up of 13·0 years, 16 363 deaths were identified. In multivariable Cox models, compared with anti-inflammatory stable individuals, risk of all-cause mortality was increased with pro-inflammatory change in men (hazard ratio (HR) = 1·13, 95 % CI 1·03, 1·23) and women (HR = 1·22, 95 % CI 1·13, 1·32). Per one-point increase in E-DII score over time, HR was 1·02 (95 % CI 1·00, 1·03) for men and 1·06 (95 % CI 1·04, 1·07) for women (P for heterogeneity < 0·001). While no heterogeneity by race and ethnicity was observed for men, the increased risk per one-point increase among women was stronger in non-Whites than in Whites (P for heterogeneity = 0·004). Our findings suggest that a change towards a more pro-inflammatory diet is associated with an increased risk of mortality both in men and women, and that the association is stronger in women, especially non-White women, than in men.

White Rice Consumption and Risk of Colorectal Cancer Among Japanese Americans: The Multiethnic Cohort Study.

BACKGROUND: White rice is a staple food for Japanese, a population at high risk for colorectal cancer (CRC). We investigated the association between white rice intake and CRC among Japanese Americans in the Multiethnic Cohort (MEC) study. METHODS: The MEC study is a prospective study established in Hawaii and California in 1993-1996. Usual dietary intake was assessed using a validated quantitative food frequency questionnaire at baseline. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of intake and to perform trend tests across sex-specific quartiles with adjustment for relevant confounders. RESULTS: We identified 1,553 invasive CRC cases among 49,136 Japanese Americans (23,595 men and 25,541 women) during a mean follow-up of 19 years. White rice consumption was not associated with overall CRC incidence in men (Ptrend = 0.11) or women (Ptrend = 0.56). After excluding participants with a history of diabetes, the inverse associations were significant for CRC (Ptrend = 0.03, HR for quartile 4 [Q4] vs quartile 1 [Q1], 0.81; 95% CI, 0.64-1.03) and tumors of the distal colon (Ptrend = 0.006, HR for Q4 vs Q1, 0.66; 95% CI, 0.44-0.99) among men but not women. CONCLUSION: White rice consumption was not associated with an increased risk of overall CRC among Japanese Americans. An inverse association was observed with risk of CRC and distal colon cancer in men without a history of diabetes.

Modifying effects of race and ethnicity and APOE on the association of physical activity with risk of Alzheimer's disease and related dementias.

INTRODUCTION: We investigated whether the protective association of physical activity with risk of Alzheimer's disease and related dementias (ADRD) has genetic or behavioral variations. METHODS: In the Multiethnic Cohort, we analyzed moderate or vigorous physical activity (MVPA) reported at ages 45 to 75 among 88,047 participants in relation to 13,039 incident diagnoses of late-onset ADRD identified in Medicare claims (1999 to 2014), by five racial and ethnic groups, hours sitting, and in a subset (16%), apolipoprotein E (APOE) genotype. RESULTS: MVPA was inversely associated with ADRD (hazard ratio for ≥14 vs <2.5 hours/week: 0.83, 95% confidence interval [CI]: 0.76 to 0.90 in men; 0.88, 5% CI: 0.81 to 0.95 in women). The association was inverse in all racial and ethnic groups except Black participants (P-heterogeneity = 0.52), but stronger in individuals with lower levels of sitting duration or those who do not carry the APOE e4 risk allele. DISCUSSION: The different effects of physical activity by sitting duration and APOE genotype warrant further research.

Racial/ethnic differences in postmenopausal breast cancer risk by hormone receptor status: The multiethnic cohort study.

There are racial/ethnic differences in the incidence of hormone receptor positive and negative breast cancer. To understand why these differences exist, we investigated associations between hormone-related factors and breast cancer risk by race/ethnicity in the Multiethnic Cohort (MEC) Study. Among 81 511 MEC participants (Native Hawaiian, Japanese American, Latina, African American and White women), 3806 estrogen receptor positive (ER+) and 828 ER- incident invasive breast cancers were diagnosed during a median of 21 years of follow-up. We used Cox proportional hazards regression models to calculate associations between race/ethnicity and breast cancer risk, and associations between hormone-related factors and breast cancer risk by race/ethnicity. Relative to White women, ER+ breast cancer risk was higher in Native Hawaiians and lower in Latinas and African Americans; ER- disease risk was higher in African Americans. We observed interaction with race/ethnicity in associations between oral contraceptive use (OC; Pint .03) and body mass index (BMI; Pint .05) with ER+ disease risk; ever versus never OC use increased risk only in Latinas and positive associations for obese versus lean BMI were strongest in Japanese Americans. For ER- disease risk, associations for OC use, particularly duration of use, were strongest for African Americans (Pint .04). Our study shows that associations of OC use and obesity with ER+ and ER- breast cancer risk differ by race/ethnicity, but established risk factors do not fully explain racial/ethnic differences in risk. Further studies are needed to identify factors to explain observed racial/ethnic differences in breast cancer incidence.

Plant-based dietary patterns defined by a priori indices and colorectal cancer risk by sex and race/ethnicity: the Multiethnic Cohort Study.

BACKGROUND: Plant-based diets assessed by a priori indices are associated with health outcomes. This study investigated the associations between pre-defined indices of plant-based diets and risk of colorectal cancer (CRC) and evaluated whether the association varies by sex, race and ethnicity, and anatomic subsite of tumors. METHODS: A total of 79,952 men and 93,475 women who participated in the Multiethnic Cohort Study were included. Primary outcome was incidence of invasive CRC. Cox models were used to estimate the risk of CRC across quintiles of three plant-based diet scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). RESULTS: During a mean follow-up of 19.2 years, 4976 incident CRC were identified. Among men, multivariable-adjusted HR (95% CI) for the highest vs. lowest quintiles was 0.77 (0.67-0.88) for PDI, and 0.80 (0.70-0.91) for hPDI, while no significant association was found for uPDI among men and for all indices among women. In men, the inverse association for PDI was stronger in Japanese American, Native Hawaiian, and White groups than African American or Latino group (P for heterogeneity = 0.01) and for left colon and rectal tumors than right tumors (P for heterogeneity = 0.005), whereas the decreased risk with hPDI was found consistently across racial and ethnic groups and subsites. CONCLUSIONS: Greater adherence to plant-based diets rich in healthy plant foods and low in less healthy plant foods is associated with a reduced risk of CRC in men, but not in women. The strength of the association among men may vary by race and ethnicity and anatomic subsite of tumors.

Diet quality and all-cause and cancer-specific mortality in cancer survivors and non-cancer individuals: the Multiethnic Cohort Study.

PURPOSE: We examined post-diagnostic diet quality in relation to all-cause and cancer-specific mortality among adults diagnosed with invasive cancer between cohort entry (45-75 years) and their 10-year follow-up, in comparison with those without invasive cancer during that period, in the Multiethnic Cohort. METHODS: Data were from 70,045 African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites (6370 with cancer, 63,675 without cancer). Diet quality was measured by the Healthy Eating Index (HEI)-2015, the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH) scores, using a food frequency questionnaire. Multivariable Cox models estimated the association of the dietary indexes at 10-year follow-up and changes since baseline with subsequent mortality. RESULTS: Post-diagnostic scores from all four indexes were associated with lower mortality: for the highest vs. lowest quartiles, hazard ratio (HR) for all-cause mortality was 0.74 (95% CI 0.67-0.82) for HEI-2015, 0.82 (0.74-0.92) for AHEI-2010, 0.74 (0.66-0.84) for aMED, and 0.82 (0.74-0.91) for DASH. The corresponding HRs for cancer mortality were 0.84 (0.71-1.00), 0.85 (0.71-1.00), 0.71 (0.59-0.85), and 0.84 (0.71-1.00). Compared to stable scores over 10 years (< 0.5 SD change), HR for all-cause mortality was 0.87 (0.79-0.97) for ≥ 1 SD increase in HEI-2015 and was 1.22 to 1.29 for ≥ 1 SD decrease in scores across the four indexes. These HRs were similar to those for participants without cancer. CONCLUSION: Post-diagnostic high-quality diet was related to lower all-cause and cancer mortality among adult cancer survivors, with risk reduction comparable to that among participants without cancer.

Risk of Alzheimer's disease and related dementia by sex and race/ethnicity: The Multiethnic Cohort Study.

INTRODUCTION: Data are limited for comparison of sex- and race/ethnicity-specific risks of Alzheimer's disease and related dementia (ADRD). METHODS: In the population-based Multiethnic Cohort, we estimated the age-standardized diagnostic incidence rate (ASDIR) and relative risk of late-onset ADRD (n = 16,410) among 105,796 participants based on Medicare claims (1999-2014) by sex and race/ethnicity. RESULTS: The ASDIR for ADRD was higher for women (17.0 per 1000 person-years) than for men (15.3) and varied across African Americans (22.9 in women, 21.5 in men), Native Hawaiians (19.3, 19.4), Latinos (16.8, 14.7), Whites (16.4, 15.5), Japanese Americans (14.8, 13.8), and Filipinos (12.5, 9.7). Similar risk patterns were observed for AD. Adjustment for education and cardiometabolic diseases attenuated the differences. Accounting for deaths from competing causes increased the sex difference, while reducing the racial/ethnic differences. Less racial/ethnic disparity was detected among apolipoprotein E (APOE) e4 carriers. DISCUSSION: More research is needed to understand the sex and racial/ethnic differences in ADRD.

Racial/ethnic differences in anthropometric and hormone-related factors and endometrial cancer risk: the Multiethnic Cohort Study.

BACKGROUND: Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women. METHODS: Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated. RESULTS: Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (pint race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (pint 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (pint 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites. CONCLUSIONS: Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.

Changes in diet quality and body weight over 10 years: the Multiethnic Cohort Study.

High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993-1996, 45-69 years) and 10-year follow-up (2003-2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55-1·17 kg in men and 0·62-1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.

Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex.

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45-75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993-1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.

Changes in Diet Quality over 10 Years Are Associated with Baseline Sociodemographic and Lifestyle Factors in the Multiethnic Cohort Study.

BACKGROUND: Trends in diet quality among US adults indicate a steady improvement, but data on longitudinal individual-level changes in diet quality are still limited. OBJECTIVE: We examined changes in diet quality over 10 y and sought to determine whether baseline sociodemographic and lifestyle factors predicted the changes in a multiethnic population. METHODS: Data were from 63,255 African American, Native Hawaiian, Japanese American, Latino, and white men and women (45-75 y old at baseline) in the Multiethnic Cohort, who completed a quantitative food frequency questionnaire at baseline (1993-1996) and 10-y follow-up (2003-2007) and had no prevalent cancer or heart disease at either survey. Overall diet quality was measured by use of the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) score. We used a general linear model with adjustment for covariates to compare diet quality changes by baseline characteristics in men and women separately. RESULTS: Overall diet quality improved over 10 y by 3.2 points in men and 2.9 in women assessed using the HEI-2015, although scores for some components worsened (saturated and trans fats, indicating increased intake) or remained unchanged at a low quality level (whole grains, dairy, and sodium). In multivariable models where changes in HEI-2015, AHEI-2010, and DASH were harmonized to a 100-point score, greater increases in scores in both men and women were found for Japanese American ethnicity (increase by 0.5-4.7 in the 3 scores, P < 0.03), higher education (by 0.5-1.5, P ≤ 0.001), normal weight (BMI 18.5 to <25, by 0.6-2.5, P ≤ 0.01), nonsmoking (by 1.5-2.7, P < 0.001), higher moderate/vigorous physical activity level (by 0.3-0.8, P ≤ 0.04), and multivitamin use (by 0.4-0.7, P < 0.001) at baseline. CONCLUSIONS: Sociodemographic and lifestyle factors, closely associated with diet quality, also predicted subsequent changes in diet quality over time in this multiethnic population.

SALM4 regulates angiogenic functions in endothelial cells through VEGFR2 phosphorylation at Tyr1175.

Angiogenesis depends on VEGF-mediated signaling. However, the regulatory mechanisms and functions of individual VEGF receptor 2 (VEGFR2) phosphorylation sites remain unclear. Here, we report that synaptic adhesion-like molecule 4 (SALM4) regulates a specific VEGFR2 phosphorylation site. SALM4 silencing in HUVECs and Salm4 knockout (KO) in lung endothelial cells (ECs) of Salm4-/- mice suppressed phosphorylation of VEGFR2 tyrosine (Y) 1175 (Y1173 in mice) and downstream signaling upon VEGF-A stimulation. However, VEGFR2 phosphorylation at Y951 (Y949 in mice) and Y1214 (Y1212 in mice) remained unchanged. Knockdown and KO of SALM4 inhibited VEGF-A-induced angiogenic functions of ECs. SALM4 depletion reduced endothelial leakage, sprouting, and migratory activities. Furthermore, in an ischemia and reperfusion (I/R) model, brain injury was attenuated in Salm4-/- mice compared with wild-type (WT) mice. In brain lysates after I/R, VEGFR2 phosphorylation at Y949, Y1173, and Y1212 were induced in WT brains, but only Y1173 phosphorylation of VEGFR2 was reduced in Salm4-/- brains. Taken together, our results demonstrate that SALM4 specifically regulates VEGFR2 phosphorylation at Y1175 (Y1173 in mice), thereby fine-tuning VEGF signaling in ECs.-Kim, D. Y., Park, J. A., Kim, Y., Noh, M., Park, S., Lie, E., Kim, E., Kim, Y.-M., Kwon, Y.-G. SALM4 regulates angiogenic functions in endothelial cells through VEGFR2 phosphorylation at Tyr1175.

Physiologic and Metabolic Changes in Crepidiastrum denticulatum According to Different Energy Levels of UV-B Radiation.

Ultraviolet B (UV-B) light, as a physical elicitor, can promote the secondary metabolites biosynthesis in plants. We investigated effects of different energy levels of UV-B radiation on growth and bioactive compounds of Crepidiastrum denticulatum. Three-week-old seedlings were grown in a plant factory for 5 weeks. Plants were subjected to different levels of UV-B (0, 0.1, 0.25, 0.5, 1.0, and 1.25 W m-2), 6 h a day for 6 days. All UV-B treatments had no negative effect on the shoot dry weight; however, relatively high energy treatments (1.0 and 1.25 W m-2) inhibited the shoot fresh weight. UV-B light of 0.1, 0.25, and 0.5 W m-2 did not affect total chlorophyll and H2O2 contents; however, they increased total carotenoid content. On 4 days, 0.25 W m-2 treatment increased antioxidant capacity, total hydroxycinnamic acids (HCAs) content, and several sesquiterpenes. Treatments with 1.0 and 1.25 W m-2 increased total carotenoid, total HCAs, and H2O2 contents, and destroyed chlorophyll pigments, reducing maximum quantum yield of photosystem II and causing visible damage to leaves. Partial least squares discrimination analysis (PLS-DA) showed that secondary metabolites were distinguishably changed according to energy levels of UV-B. The potential of 0.25 W m-2 UV-B for the efficient production of bioactive compounds without growth inhibition in C. denticulatum was identified.

Alcohol Intake and Colorectal Cancer Risk in the Multiethnic Cohort Study.

To investigate the association of alcohol intake with colorectal cancer risk according to race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical subsite, we analyzed data from 190,698 black, Native Hawaiian, Japanese-American, Latino, and white persons in Hawaii and California in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993-2013). In multivariate Cox regression models, the hazard ratio was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0-29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day among men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, among women, compared with nondrinkers (P for heterogeneity according to sex = 0.74). An increased risk was apparent among Native Hawaiians, Japanese Americans, Latinos, and white persons and among individuals with body mass index <25.0 (calculated as weight (kg)/height (m)2), never-users of nonsteroidal antiinflammatory drugs, and those with lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left-colon tumors than for right-colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies according to race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.