Yurii B. Shvetsov

Associations of key diet-quality indexes with mortality in the Multiethnic Cohort: the Dietary Patterns Methods Project

BACKGROUND Healthy dietary patterns have been linked positively with health and longevity. However, prospective studies in diverse populations in the United States addressing dietary patterns and mortality are limited. OBJECTIVE We assessed the ability of the following 4 diet-quality indexes [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)] to predict the reduction in risk of mortality from all causes, cardiovascular disease (CVD), and cancer. DESIGN White, African American, Native Hawaiian, Japanese American, and Latino adults (n = 215,782) from the Multiethnic Cohort completed a quantitative food-frequency questionnaire. Scores for each dietary index were computed and divided into quintiles for men and women. Mortality was documented over 13-18 y of follow-up. HRs and 95% CIs were computed by using adjusted Cox models. RESULTS High HEI-2010, AHEI-2010, aMED, and DASH scores were all inversely associated with risk of mortality from all causes, CVD, and cancer in both men and women (P-trend < 0.0001 for all models). For men, the HEI-2010 was consistently associated with a reduction in risk of mortality for all causes (HR: 0.75; 95% CI: 0.71, 0.79), CVD (HR: 0.74; 95% CI: 0.69, 0.81), and cancer (HR: 0.76; 95% CI: 0.70, 0.83) when lowest and highest quintiles were compared. In women, the AHEI and aMED showed large reductions for all-cause mortality (HR: 0.78; 95% CI: 0.74, 0.82), the AHEI showed large reductions for CVD (HR: 0.76; 95% CI: 0.69, 0.83), and the aMED showed large reductions for cancer (HR: 0.84; 95% CI: 0.76, 0. 92). CONCLUSION These results, in a US multiethnic population, suggest that consuming a dietary pattern that achieves a high diet-quality index score is associated with lower risk of mortality from all causes, CVD, and cancer in adult men and women.

Circumcision and Human Papillomavirus Infection in Men: A Site-Specific Comparison

BACKGROUND Lack of circumcision has been identified as a risk factor for male genital human papillomavirus (HPV) infection, although this association has not been consistently supported. METHODS Specimens for HPV testing were collected from a cohort of 379 (primarily heterosexual) adult males. HPV prevalence in the glans penis and coronal sulcus, penile shaft, scrotum, semen, and urine was compared by circumcision status. RESULTS Overall, HPV DNA prevalence ranged from 6% in semen to 52% in the penile shaft. The prevalence of any HPV infection in the glans/corona was significantly higher in uncircumcised men (46%) than in circumcised men (29%) (odds ratio [OR], 1.96 [95% confidence interval (CI), 1.02-3.75], adjusted for demographic characteristics and sexual history). Uncircumcised men also had an increased risk of oncogenic HPV infection (adjusted OR, 2.51 [95% CI, 1.11-5.69]) and infection with multiple HPV types (adjusted OR, 3.56 [95% CI, 1.50-8.50]). Among uncircumcised men, HPV prevalence in the foreskin (44%) was comparable to that in the glans/corona, and type-specific positivity was observed between the 2 sites (kappa=0.52). CONCLUSIONS Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV, specifically localized to the glans/corona, possibly because of its proximity to the foreskin, which may be particularly vulnerable to infection.

Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study

Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2-56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs.

Acquisition of Anal Human Papillomavirus (HPV) Infection in Women: the Hawaii HPV Cohort Study

BACKGROUND The majority of anal cancer is associated with human papillomavirus (HPV) infection, yet little is known about womens risk of acquisition of anal HPV infection. METHODS Risk factors for the acquisition of anal HPV infection were examined in a longitudinal cohort study of 431 women, via repeated measurement of HPV DNA. RESULTS Seventy percent of women were positive for anal HPV infection at one or more clinic visits from baseline through a follow-up period that averaged 1.3 years. The incidence of a high-risk (HR) infection was 19.5 (95% confidence interval [CI], 16.0-23.6) per 1000 woman-months. The most common incident HR HPV types were HPV-53, -52 and -16. The presence of an HR anal HPV infection at baseline increased the risk of an incident anal infection by 65%. Baseline HR cervical HPV infection also predicted the acquisition of an HR anal HPV infection (odds ratio, 1.81 [95% CI, 1.09-3.02]). Nonviral risk factors for acquisition of HR HPV infection included younger age, lower socioeconomic status, greater lifetime number of sexual partners, past use of hormones, and condom use. CONCLUSIONS The results of this study suggest that womens risk of anal HPV infection is as common as their risk of cervical HPV infection.

Incidence of Ovarian, Peritoneal, and Fallopian Tube Carcinomas in the United States, 1995-2004

Objective: The objective of this analysis was to describe the distribution of pelvic carcinomas in the United States by demographic, pathologic, and clinical features. Methods: Carcinomas of the ovary (n = 112,541), peritoneum (n = 6,458), and fallopian tube (n = 3,479) were identified through 24 population-based registries in the United States during the period 1995 to 2004. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. Results: The age-adjusted incidence rate for ovarian carcinoma (119.9 per million) was substantially higher than for peritoneal (6.78 per million) or fallopian tube (3.72 per million) carcinomas. White women had the highest rates for all three malignancies. Rates for peritoneal carcinoma were lowest among Black women (2.88 per million) and rates for fallopian tube carcinoma were lowest among Hispanic women (2.45 per million). Serous carcinomas were the most commonly diagnosed histologic type for all anatomic sites. Peritoneal carcinomas were diagnosed at later ages (mean, 67 years) and more advanced stages (85% regional/distant) compared with fallopian tube carcinomas (mean, 64 years; 62% regional/distant) and ovarian carcinomas (mean, 63 years; 76% regional/distant). Incidence for all three pelvic carcinomas was lowest in the South. Time trend analyses between 1973 and 2005 exhibited a significant decline in ovarian carcinoma incidence and rises in the rates of peritoneal and fallopian tube cancers. Conclusions: Similarities in the incidence patterns for ovarian, peritoneal, and fallopian tube carcinomas support the likelihood of a common molecular pathogenesis. (Cancer Epidemiol Biomarkers Prev 2009;18(1):132–9)

Sequential Acquisition of Human Papillomavirus (HPV) Infection of the Anus and Cervix: The Hawaii HPV Cohort Study

BACKGROUND Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. METHODS he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). RESULTS Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. CONCLUSIONS It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Duration and Clearance of Anal Human Papillomavirus (HPV) Infection among Women: The Hawaii HPV Cohort Study

BACKGROUND The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. METHODS Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. RESULTS Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. CONCLUSIONS The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.

Prediagnostic Leptin, Adiponectin, C-Reactive Protein, and the Risk of Postmenopausal Breast Cancer

Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case–control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37–2.75); Ptrend ≤ 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36–2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01–1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188–95. ©2013 AACR.

Urinary Phytoestrogen Excretion and Postmenopausal Breast Cancer Risk: The Multiethnic Cohort Study

The objective of this study was to examine the association of urinary phytoestrogens with the risk of postmenopausal breast cancer. Participants in the Multiethnic Cohort Study included 36,458 postmenopausal women who provided blood or urine specimens. A nested case-control study of breast cancer with biospecimens was created in which cases diagnosed after specimen collection were matched to two controls. Two hundred fifty-one women with breast cancer and 462 controls had urine available for analysis of urinary phytoestrogens. Odds ratios (OR) and 95% confidence intervals (CI) were obtained using conditional logistic regression. A nonmonotonic inverse trend (P = 0.04) in breast cancer risk was associated with increasing urinary excretion of genistein (OR 25th-75th percentile, 0.88; 95% CI, 0.78-0.99) and total isoflavones (OR 25th-75th percentile, 0.80; 95% CI, 0.65-0.99). A significant reduction in breast cancer risk in Japanese-American women was associated with the highest compared with the lowest quartile excretion of urinary daidzein (OR, 0.41; 95% CI, 0.19-0.89; Ptrend, 0.005). The risk of breast cancer was reduced among White women with the highest compared with the lowest quartile excretion of equol (OR, 0.27; 95% CI, 0.08-0.95), although the trend in risk was not significant (P = 0.07). Our results provide some support to the hypothesis that a diet rich in isoflavones from soy products reduces the risk of postmenopausal breast cancer, particularly in populations with comparatively high excretion of phytoestrogens.

Demographic and Pathologic Differences in the Incidence of Invasive Penile Cancer in the United States, 1995-2003

Objective: Penile cancer is an uncommon malignancy, so few descriptive or analytic studies have been reported in the literature. The objective of this analysis was to describe the distribution of penile cancer in the United States by demographic, pathologic, and clinical features. Methods: Penile cancer among 6,539 men was identified through 29 population-based registries in the United States during the period 1995-2003. These registries were estimated to represent 68% of the U.S. population. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. A subset of nine registries was used to examine time trends in penile cancer between 1973 and 2003. Results: Squamous cell carcinomas were the most common histologic type of penile cancer, representing 93% of all malignancies. Hispanic men had the highest age-adjusted incidence rates per million for penile cancer (6.58 per million), followed by Blacks (4.02 per million), Whites (3.90 per million), American Indians (2.81 per million), and Asian-Pacific Islanders (2.40 per million). The highest rates of penile cancer were found among Hispanic men (46.9 per million) and Black men (36.2 per million) of ages ≥85 years. Penile malignancy was rare among males under age 20 years. Time trend analysis supported a significant decrease in the incidence of penile cancer for Blacks (annual percent change, −1.9%) and Whites (annual percent change, −1.2%). The majority (61%) of penile cancers were diagnosed at a localized stage among all racial and ethnic groups, although Hispanic and Black men tended to be diagnosed at more advanced stages than Whites. No racial or ethnic differences in tumor grade were identified. The incidence of penile cancer was highest in the South (4.42 per million) and lowest in the West (3.28 per million) of the United States. The highest age-adjusted incidence rate was found among Black men in the South (4.77 per million) and the lowest rate among Asian-Pacific Islanders in the West (1.84 per million). Conclusions: This analysis showed significant racial/ethnic and regional variation in the incidence of penile cancer. The high rate of penile cancer among Hispanic and Southern Black men suggests differences in risk factors for this malignancy, such as circumcision, hygiene, or human papillomavirus exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1833–9)