Interactions between serum folate and human papillomavirus with cervical intraepithelial
      neoplasia risk in a Chinese population-based study

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ABSTRACT

Background

Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied.

Objective

The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN.

Design

We performed a cross-sectional analysis of screening data in 2304 women aged 19–65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk.

Results

After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR = 1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall < 0.01, P-nonlinearity = 0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction < 0.01).

Conclusions

Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women.

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Most cited references 45

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Cancer statistics in China, 2015.

Wanqing Chen, Rongshou Zheng, Peter D Baade … (2016)

With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.

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Global cancer statistics, 2012.

Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

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Dose-response analyses using restricted cubic spline functions in public health research.

Loïc Desquilbet, François Mariotti (2010)

Taking into account a continuous exposure in regression models by using categorization, when non-linear dose-response associations are expected, have been widely criticized. As one alternative, restricted cubic spline (RCS) functions are powerful tools (i) to characterize a dose-response association between a continuous exposure and an outcome, (ii) to visually and/or statistically check the assumption of linearity of the association, and (iii) to minimize residual confounding when adjusting for a continuous exposure. Because their implementation with SAS® software is limited, we developed and present here an SAS macro that (i) creates an RCS function of continuous exposures, (ii) displays graphs showing the dose-response association with 95 per cent confidence interval between one main continuous exposure and an outcome when performing linear, logistic, or Cox models, as well as linear and logistic-generalized estimating equations, and (iii) provides statistical tests for overall and non-linear associations. We illustrate the SAS macro using the third National Health and Nutrition Examination Survey data to investigate adjusted dose-response associations (with different models) between calcium intake and bone mineral density (linear regression), folate intake and hyperhomocysteinemia (logistic regression), and serum high-density lipoprotein cholesterol and cardiovascular mortality (Cox model). 2010 John Wiley & Sons, Ltd.

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Author and article information

Journal

Title: The American Journal of Clinical Nutrition

Publisher: Oxford University Press (OUP)

ISSN (Print): 0002-9165

ISSN (Electronic): 1938-3207

Publication date Created: November 2018

Publication date Created: November 01 2018

Publication date Created: September 20 2018

Publication date Other: November 2018

Publication date (Print): November 01 2018

Publication date (Electronic): September 20 2018

Volume: 108

Issue: 5

Pages: 1034-1042

Affiliations

[1 ]Departments of Obstetrics and Gynecology

[2 ]School of Public Health, The University of Hong Kong, Hong Kong SAR, China

[3 ]School of Public Health, Brown University, Providence, RI

[4 ]Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China

[5 ]Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, Huhhot, China

[6 ]Department of Obstetrics and Gynecology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China

[7 ]Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

[8 ]Pathology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

Article

DOI: 10.1093/ajcn/nqy160

PubMed ID: 30247499

SO-VID: 5f8b21a2-4b7e-44cc-8ad9-0921ba5cdee3

License:

https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

Interactions between serum folate and human papillomavirus with cervical intraepithelial neoplasia risk in a Chinese population-based study

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ABSTRACT

Background

Objective

Design

Results

Conclusions

Related collections

Recursive Rule based Visual Categorization

Most cited references 45

Cancer statistics in China, 2015.

Global cancer statistics, 2012.

Dose-response analyses using restricted cubic spline functions in public health research.

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