Lynne R. Wilkens

Association between various sedentary behaviours and all-cause, cardiovascular disease and cancer mortality: the Multiethnic Cohort Study

BACKGROUNDnIt has been proposed that time spent sitting increases all-cause mortality, but evidence to support this hypothesis, especially the relative effects of various sitting activities alone or in combination, is very limited.nnnMETHODSnThe association between various sedentary behaviours (time spent: sitting watching television (TV); in other leisure activities; in a car/bus; at work; and at meals) and mortality (all-cause and cause-specific) was examined in the Multiethnic Cohort Study, which included 61 395 men and 73 201 women aged 45-75 years among five racial/ethnic groups (African American, Latino, Japanese American, Native Hawaiian and White) from Hawaii and Los Angeles, USA.nnnRESULTSnMedian follow-up was 13.7 years and 19 143 deaths were recorded. Total daily sitting was not associated with mortality in men, whereas in women the longest sitting duration (≥ 10 h/day vs <5 h/day) was associated with increased all-cause (11%) and cardiovascular (19%) mortality. Multivariate hazard ratios (HR) for ≥ 5 h/day vs <1 h/day of sitting watching TV were 1.19 in men (95% confidence interval (CI) 1.10-1.29) and 1.32 in women (95% CI 1.21-1.44) for all-cause mortality. This association was consistent across four racial/ethnic groups, but was not seen in Japanese Americans. Sitting watching TV was associated with an increased risk for cardiovascular mortality, but not for cancer mortality. Time spent sitting in a car/bus and at work was not related to mortality.nnnCONCLUSIONSnLeisure time spent sitting, particularly watching television, may increase overall and cardiovascular mortality. Sitting at work or during transportation was not related to mortality.

Racial/Ethnic Differences in Colorectal Cancer Risk: The Multiethnic Cohort Study

Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age‐adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow‐up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable‐adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09–1.48; women, RR = 1.49, 95% CI = 1.24–1.78) and African American women (RR = 1.48, 95% CI = 1.23–1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site‐specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.

Abstract B32: Evaluating genetic risk for prostate cancer among Japanese Americans and Latinos: The Multiethnic Cohort Study

Prostate cancer displays dramatic differences in incidence rates across racial/ethnic groups. The genetic basis of prostate cancer may depend in part on race/ethnicity, which may partially account for the variability in prostate cancer rates across racial/ethnic groups. To search for novel risk variants for prostate cancer, within the Multiethnic Cohort Study we conducted a genome-wide association study of men of Japanese and Latino ancestry, two populations that have a lower burden of this disease. In addition, we tested established risk variants for prostate cancer and utilized these variants to develop genetic risk models of prostate cancer. For Japanese Americans (case/controls=1,033/1042), we identified 69 SNPs associated with prostate cancer risk at P < 1.0×10-4 outside of known risk regions. The most notable association was seen with rs1093117 at chromosome 2 (P=1.23×0-7). For 57 of the established risk variants for prostate cancer, 20 variants were significantly associated with prostate cancer in Japanese Americans. The cumulative effect of these risk alleles resulted in a 12% increased risk of disease for each additional allele (P=2.08×10-25), with Japanese American men in the top quartile of the risk allele distribution having a 3.2-fold increased risk of prostate cancer compared to those in the lowest quartile (P = 8.47×10-20). For Latinos (cases/controls=1,043/1,057), outside of known risk regions, 56 SNPs were associated with prostate cancer risk at P < 1.0×10-4 and rs4240731 at chromosome 12 was most strongly associated with disease (P = 2.60×10-6). For the 57 risk variants for prostate cancer, 19 variants were significantly associated with disease in Latinos. The cumulative effect of prostate cancer risk alleles resulted in a 9% increased risk of prostate cancer for each additional risk allele (P=2.67×10-6) and those in the highest risk quartile had a 2.7-fold increased risk of prostate cancer in comparison to men in the lowest risk quartile (P=1.55×10-13). In summary, our findings suggest established risk variants for prostate cancer significantly contribute to disease susceptibility and future work will examine replication of genome-wide association findings in independent panels of Japanese and Latino men.nnCitation Format: Iona C. Cheng, Daniel O. Stram, Laurence N. Kolonel, Brian E. Henderson, Loic Le Marchand, Christopher A. Haiman, Gary K. Chen, Jing He, Peggy Wan, Xin Sheng, Loreall C. Pooler, Lynne R. Wilkens, Kristine R. Monroe. Evaluating genetic risk for prostate cancer among Japanese Americans and Latinos: The Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B32.

Abstract A110: Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer

A strong association between chronic inflammation and colorectal cancer (CRC) risk has been observed. We postulated that common variation in genes involved in the inflammation and innate immunity pathways may result in a chronic pro-inflammatory state that may lead to increased CRC risk. We comprehensively examined the associations of 724 tagSNPs in 37 key genes in these pathways with CRC in two large well-characterized studies. The screening phase included 2,322 discordant sibships (2,535 cases, 3,915 unaffected sibling controls) from the Colon Cancer Family Registry. Nineteen gene regions spanned by 99 top hits from main-effect or interaction-effect analyses in phase 1 were followed up by genotyping 351 well-chosen tagSNPs in 4,783 subjects (2,153 cases, 2,630 controls) in five ethnic groups in the Multiethnic Cohort Study. One SNP rs9858822 in PPAR gamma gene was statistically significantly associated with CRC in the replication phase (p=1.5 × 10-4, odds ratio per allele = 1.36), based on a conservative Bonferroni-corrected significance level 0.05 adjusted for the “effective” number of markers (n=306). The risk allele C was common (frequency 0.3) in African Americans but was rare (frequency < 0.05) in Whites, Japanese Americans, Latinos and Native Hawaiians. We did not detect effect modification by race/ethnicity, BMI, or use of aspirin. Strong, although not statistically significant, associations were also observed for SNPs in the neighborhood region of rs9858822 (p-values as low as 2.5 × 10-4). Further replication is needed. Citation Format: Hansong Wang, Darin Taverna, Daniel O. Stram, Iona Cheng, Lynne R. Wilkens, Terrilea Burnett, Polly A. Newcomb, Laurence N. Kolonel, Brian E. Henderson, David Duggan, Cornelia M. Ulrich, Loic Le Marchand. Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A110.

Dietary and other correlates of melanoma in Hawaii: preliminary findings

The relationship of diet to malignant melanoma has remained rela tively unexplored. However, there is evidence, primarily from labora tory studies, that dietary factors may play a role in the etiology of melanoma [1]. Retinoids appear to inhibit the growth of murine and human melanoma cell lines [2,3], as well as that of transplanted melanocytic tumors in mice [4]. There has also been one report of successful treatment of melanoma with trans-retinoic acid [5].