Kami K. White

Plasma Levels of B Vitamins and Colorectal Cancer Risk: The Multiethnic Cohort Study

B vitamins, such as folate, vitamin B6, and vitamin B12, play an important role as coenzymes in one-carbon metabolism and may affect colorectal cancer risk. We aimed to comprehensively investigate the relationships of plasma folate, pyridoxal-5′-phosphate (PLP, the active form of vitamin B6), vitamin B12, methylmalonic acid, homocysteine, and cysteine with colorectal cancer risk, accounting for suspected modifiers (alcohol intake, MTHFR C677T genotype, and plasma C-reactive protein) and potential confounders. We conducted a case-control study nested within the Multiethnic Cohort study and analyzed prospectively collected blood samples from 224 incident colorectal cancer cases and 411 controls matched on age, sex, race/ethnicity, study site, date/time of blood draw, and hours of fasting. We found an inverse association between plasma PLP levels and colorectal cancer, with odds ratios (95% confidence intervals) for increasing quartiles of 1.00, 0.84 (0.51-1.40), 0.62 (0.37-1.03), and 0.49 (0.29-0.83), with P trend = 0.009. This association was not explained by an association with plasma folate, seemed to be stronger at low levels of alcohol intake and among individuals with the MTHFR 677TT genotype, and was independent of plasma C-reactive protein levels. An inverse association with plasma folate was also observed among individuals with a low level of alcohol intake. These data suggest an independent role for vitamin B6 in reducing colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2195–201)

Body size and breast cancer risk: the Multiethnic Cohort.

The influence of body size on postmenopausal breast cancer risk was investigated among five racial/ethnic groups in the Multiethnic Cohort. Participants were 45–75 years old at recruitment (1993–1996), living in Hawaii and California. Of the 82,971 White, African American, Native Hawaiian, Japanese and Latina women included in this analysis, 3,030 were diagnosed with invasive breast cancer. Body mass index (BMI), height, weight and adulthood weight gain were associated with a significantly higher risk and, with the exception of height, were found to vary across ethnic groups. Native Hawaiians and Japanese with a BMI ≥30.0 compared to 20.0–24.9 kg/m2 had the highest risk (hazard ratio = 1.82, 95% confidence interval: 1.31, 2.54, p‐trend = 0.001, and hazard ratio = 1.59, 95% confidence interval: 1.24, 2.05, p‐trend < 0.0001, respectively). Current hormone replacement therapy use modified the impact of a high BMI, as non‐ and former users had a significantly higher risk compared to current users. BMI also had a more pronounced risk for advanced tumors compared to localized tumors. When both BMI and adult weight gain were analyzed simultaneously, adult weight gain, rather than BMI, was a significant risk factor overall. These findings emphasize the significance of maintaining a healthy weight throughout adulthood for the prevention of postmenopausal breast cancer.

Surviving and Thriving With Cancer Using a Web-Based Health Behavior Change Intervention: Randomized Controlled Trial

Background Given the substantial improvements in cancer screening and cancer treatment in the United States, millions of adult cancer survivors live for years following their initial cancer diagnosis and treatment. However, latent side effects can occur and some symptoms can be alleviated or managed effectively via changes in lifestyle behaviors. Objective The purpose of this study was to test the effectiveness of a six-week Web-based multiple health behavior change program for adult survivors. Methods Participants (n=352) were recruited from oncology clinics, a tumor registry, as well as through online mechanisms, such as Facebook and the Association of Cancer Online Resources (ACOR). Cancer survivors were eligible if they had completed their primary cancer treatment from 4 weeks to 5 years before enrollment. Participants were randomly assigned to the Web-based program or a delayed-treatment control condition. Results In total, 303 survivors completed the follow-up survey (six months after completion of the baseline survey) and participants in the Web-based intervention condition had significantly greater reductions in insomnia and greater increases in minutes per week of vigorous exercise and stretching compared to controls. There were no significant changes in fruit and vegetable consumption or other outcomes. Conclusions The Web-based intervention impacted insomnia and exercise; however, a majority of the sample met or exceeded national recommendations for health behaviors and were not suffering from depression or fatigue at baseline. Thus, the survivors were very healthy and well-adjusted upon entry and their ability to make substantial health behavior changes may have been limited. Future work is discussed, with emphasis placed on ways in which Web-based interventions can be more specifically analyzed for benefit, such as in regard to social networking. Trial Registration Clinicaltrials.gov NCT00962494; http://www.clinicaltrials.gov/ct2/show/NCT00962494 (Archived by WebCite at http://www.webcitation.org/6NIv8Dc6Q).

Plasma sex hormone concentrations and breast cancer risk in an ethnically diverse population of postmenopausal women: the Multiethnic Cohort Study

To add to the existing evidence that comes mostly from White populations, we conducted a nested case-control study to examine the association between sex hormones and breast cancer risk within the Multiethnic Cohort that includes Japanese American, White, Native Hawaiian, African American, and Latina women. Of the postmenopausal women for whom we had a plasma sample, 132 developed breast cancer during follow-up. Two controls per case, matched on study area (Hawaii, Los Angeles), ethnicity/race, birth year, date and time of blood draw and time fasting, were randomly selected from the women who had not developed breast cancer. Levels of estradiol (E(2)), estrone (E(1)), androstenedione, dehydroepiandrosterone (DHEA), and testosterone were quantified by RIA after organic extraction and Celite column partition chromatography. E(1) sulfate, DHEA sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were quantified by direct immunoassays. Based on conditional logistic regression, the sex hormones were positively associated and SHBG was negatively associated with breast cancer risk. All associations, except those with DHEAS and testosterone showed a significant linear trend. The odds ratio (OR) associated with a doubling of E(2) levels was 2.26 (95% confidence interval (CI) 1.58-3.25), and the OR associated with a doubling of testosterone levels was 1.34 (95% CI 0.98-1.82). The associations in Japanese American women, who constituted 54% of our sample, were similar to or nonsignificantly stronger than in the overall group. This study provides the best evidence to date that the association between sex hormones and breast cancer risk is generalizable to an ethnically diverse population.

Smoking and Colorectal Cancer: Different Effects by Type of Cigarettes?

Although smoking is suggested to be a risk factor for colorectal cancer, the evidence to date is conflicting and may be confounded. Moreover, the effect of tobacco smoke may vary by time since initiation, type of tobacco product, anatomic subsites, and among ethnic groups. Data were derived from two consecutive population-based case-control studies conducted among Caucasians, Japanese, Native Hawaiians, Filipinos, and Chinese in Hawaii, including 1,959 ethnicity-, sex-, and age-matched case-control pairs. A lifetime history of smoking for different tobacco products and information on other risk factors were obtained by in-person interviews. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated using conditional logistic regression models with adjustment for potential confounders. Subjects who ever smoked were at an increased risk of colorectal cancer compared with never smokers (OR, 1.23; 95% CI, 0.99-1.52 for men and OR, 1.27; 95% CI, 1.01-1.59 for women). Increasing quartiles of pack-years over all tobacco products showed a clear dose-dependent association in men [for the highest quartile, Q4 (>40 pack-years) versus never smokers: OR, 1.48; 95% CI, 1.12-1.96; Ptrend = 0.002]. The dose-response trend was also present in women [for the highest quartile, Q4 (>30 pack-years) versus never smokers: OR, 1.38; 95% CI, 0.91-1.95; Ptrend = 0.04] and each ethnic group. There was a suggestion of a difference in risk with type of tobacco product. Non-filtered cigarettes increased risk of both colon and rectal cancer [for Q4 versus never smokers: OR, 1.59; 95% CI, 1.15-2.21; Ptrend = 0.001 and OR, 1.84; 95% CI, 1.18-2.86; Ptrend = 0.02, respectively], whereas filtered cigarettes seemed to increase risk of rectal but not colon cancer (OR, 1.37; 95% CI, 0.88-2.13; Ptrend = 0.06 and OR, 1.05; 95% CI, 0.79-1.39; Ptrend = 0.98, respectively). The effect of smoking was not limited to the distant past, and accumulated pack-years of smoking seemed to be more important than the time in which smoking occurred. The data from this large study corroborate previous reports of a positive association between smoking and colorectal cancer and suggest that the association may vary by type of cigarette. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1341–7)

Alcohol consumption and breast cancer risk among women from five ethnic groups with light to moderate intakes: The Multiethnic Cohort Study

Higher alcohol consumption, even at moderate levels, has been associated with an increased risk of breast cancer in epidemiological studies. However, prior studies were conducted in mostly white populations. To assess the relationship of alcohol consumption to postmenopausal breast cancer risk in a multiethnic population of largely never, light or moderate drinkers, we prospectively examined the association in 85,089 women enrolled in the Multiethnic Cohort in Hawaii and California. During a mean follow‐up of 12.4 years, 3,885 incident invasive breast cancer cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models, controlling for potential confounders. Higher alcohol consumption was associated with increased risk of breast cancer: compared to nondrinkers, HRs were 1.23 (95% CI: 1.06–1.42), 1.21 (95% CI: 1.00–1.45), 1.12 (95% CI: 0.95–1.31) and 1.53 (95% CI: 1.32–1.77) for 5–9.9, 10–14.9, 15–29.9 and ≥30 g/day of alcohol, respectively. The positive association was seen in African American, Japanese American, Latino and white, but not in Native Hawaiian women, and in those with tumors that were both positive and negative for estrogen and progesterone receptors (ER/PR). This prospective study supports previous findings that light to moderate alcohol consumption increases breast cancer risk, and demonstrates this association in several ethnic groups besides whites, independent of ER/PR status.

Biomonitoring the Cooked Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine in Hair: Impact of Exposure, Hair Pigmentation, and Cytochrome P450 1A2 Phenotype

Background: Hair is a promising tissue to assess exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen formed in cooked meats. However, an understanding of how dietary exposure to PhIP, cytochrome P450 1A2 activity—a key enzyme involved in PhIP metabolism, and hair pigmentation affect the level of PhIP accrued in hair is required to determine the reliability of the PhIP hair level as a biomarker of exposure to this carcinogen. Methods: We examined the impact of PhIP exposure, cytochrome P450 1A2 activity, and hair pigmentation on the levels of PhIP accumulated in the hair of volunteers on a 4-week semicontrolled diet of cooked meat containing known quantities of PhIP. Results: The amount of PhIP in hair increased, on average, 15-fold in light- and dark-haired individuals during consumption of cooked meat. PhIP levels in hair were correlated to PhIP intake (ρ = 0.53; P < 0.001), and the relationship was strengthened when PhIP levels were normalized for the melanin content of hair (ρ = 0.71; P < 0.001). However, PhIP accrual in hair was not correlated to cytochrome P450 1A2 activity, as assessed by the caffeine test, or to the levels of unmetabolized PhIP in urine or to the metabolic ratio of the major urinary metabolite N2-(β-1-glucosiduronyl-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine to unmetabolized PhIP. Conclusions: The use of the PhIP hair biomarker should take hair pigmentation into account for accurate exposure assessment of PhIP. Impact: PhIP hair levels can serve as a biomarker in epidemiologic studies investigating the association of heterocyclic aromatic amine (HAA), cooked meat, and cancer risk. Cancer Epidemiol Biomarkers Prev; 22(3); 356–64. ©2013 AACR.

Effectiveness of a 12-month randomized clinical trial to increase physical activity in multiethnic postpartum women: Results from Hawaii's Nā Mikimiki Project ☆ ☆☆ ★

OBJECTIVE Few postpartum ethnic minority women perform leisure-time moderate-to-vigorous physical activity (MVPA). The study tested the effectiveness of a 12-month tailored intervention to increase MVPA in women with infants 2-12months old. METHODS From 2008 to 2011, women (n=311) with infants (average age=5.7months) from Honolulu, Hawaii were randomly assigned to receive tailored telephone calls and access to a mom-centric website (n=154) or access to a standard PA website (n=157). MVPA was measured at baseline, 6, and 12months using self-report and acclerometers. RESULTS Controlling for covariates, the tailored condition significantly increased self-reported MVPA from an average of 44 to 246min/week compared with 46 to 156min/week for the standard condition (p=0.027). Mothers with≥2 children had significantly greater increases in MVPA in response to the tailored intervention than those with one child (p=0.016). Accelerometer-measured MVPA significantly increased over time (p=0.0001), with no condition differences. There was evidence of reactivity to initially wearing accelerometers; the tailored intervention significantly increased MVPA among women with low baseline accelerometer MVPA minutes, but not among those with high minutes (pinteraction=0.053). CONCLUSION A tailored intervention effectively increased MVPA over 12months in multiethnic women with infants, particularly those with more than one child.

Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: A feeding study

Hair measurement of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a promising biomarker of exposure to this carcinogen formed in cooked meats. However, the dose relationship between normal range intake and hair levels and the modulating effects of CYP1A2 metabolism and hair melanin need to be evaluated. We conducted a randomized, cross-over feeding study among 41 non-smokers using ground beef cooked to two different levels of doneness, 5 days a week for 1 month. PhIP was measured by liquid chromatography/mass spectrometry in food (mean low dose = 0.72 µg/serving; mean high dose = 2.99 µg/serving), and change in PhIP hair level was evaluated. CYP1A2 activity was assessed in urine with the caffeine challenge test and head hair melanin was estimated by UV spectrophotometry. We observed a strong dose-dependent increase in hair PhIP levels. This increase was highly correlated with dose received (ρ = 0.68, P < 0.0001). CYP1A2 activity and normalizing for hair melanin did not modify the response to the intervention. Consumption of PhIP at doses similar to those in the American diet results in a marked dose-dependent accumulation of PhIP in hair. Hair PhIP levels may be used as a biomarker of dietary exposure in studies investigating disease risk.

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts

BACKGROUND Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.