Observational Study Open Access
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. Dec 10, 2015; 7(18): 1300-1305
Published online Dec 10, 2015. doi: 10.4253/wjge.v7.i18.1300
Race and colorectal cancer screening compliance among persons with a family history of cancer
Adeyinka O Laiyemo, Hassan Ashktorab, Division of Gastroenterology, Department of Medicine, Howard University College of Medicine, Washington, DC 20060, United States
Nicole Thompson, Carla D Williams, Kolapo A Idowu, Howard University Cancer Center, Washington, DC 20060, United States
Kathy Bull-Henry, Department of Medicine, Georgetown University, Washington, DC 20007, United States
Zaki A Sherif, Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC 20060, United States
Edward L Lee, Hassan Brim, Department of Pathology, Howard University, Washington, DC 20060, United States
Elizabeth A Platz, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States
Elizabeth A Platz, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, United States
Duane T Smoot, Department of Medicine, Meharry Medical Center, Nashville, TN 37208, United States
Author contributions: All authors contributed to this manuscript.
Supported by In part grant awards from Charles and Mary Latham Funds, the National Center for Advancing Translational Science, Nos. KL2TR000102-04 and UL1RT000101; the National Institute for Diabetes, Digestive Diseases and Kidney, No. R21DK100875; National Institutes of Health (to Dr Laiyemo); and Dr. Platz was supported by NCI P30 CA006973.
Institutional review board statement: The study was approved (exempt) by the Institutional Review Board of Howard University, Washington DC (Reference = IRB-14-MED-28).
Informed consent statement: Not applicable: This is an analysis of de-identified publicly available data.
Conflict-of-interest statement: None.
Data sharing statement: Not applicable. The data is publicly available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Adeyinka O Laiyemo, MD, MPH, Division of Gastroenterology, Department of Medicine, Howard University College of Medicine, 2041 Georgia Avenue, NW, Washington, DC 20060, United States. adeyinka.laiyemo@howard.edu
Telephone: +1-202-8657186 Fax: +1-202-8654607
Received: July 22, 2015
Peer-review started: July 24, 2015
First decision: August 25, 2015
Revised: September 18, 2015
Accepted: October 23, 2015
Article in press: October 27, 2015
Published online: December 10, 2015

Abstract

AIM: To determine compliance to colorectal cancer (CRC) screening guidelines among persons with a family history of any type of cancer and investigate racial differences in screening compliance.

METHODS: We used the 2007 Health Information National Trends Survey and identified 1094 (27.4%) respondents (weighted population size = 21959672) without a family history of cancer and 3138 (72.6%) respondents (weighted population size = 58201479) with a family history of cancer who were 50 years and older. We defined compliance with CRC screening as the use of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared compliance with CRC screening among those with and without a family member with a history of cancer.

RESULTS: Overall, those with a family member with cancer were more likely to be compliant with CRC screening (64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). The absolute increase in screening rates associated with family history of cancer was 8.2% among whites. Hispanics had lowest screening rates among those without family history of cancer 41.9% but had highest absolute increase (14.7%) in CRC screening rate when they have a family member with cancer. Blacks had the lowest absolute increase in CRC screening (5.3%) when a family member has a known history of cancer. However, the noted increase in screening rates among blacks and Hispanics when they have a family member with cancer were not higher than whites without a family history of cancer: (54.5% vs 58.7%; OR = 1.16; 95%CI: 0.72-1.88) for blacks and (56.7% vs 58.7%; OR = 1.25; 95%CI: 0.72-2.18) for Hispanics.

CONCLUSION: While adults with a family history of any cancer were more likely to be compliant with CRC screening guidelines irrespective of race/ethnicity, blacks and Hispanics with a family history of cancer were less likely to be compliant than whites without a family history. Increased burden from CRC among blacks may be related to poor uptake of screening among high-risk groups.

Key Words: Colon cancer, Health disparities, Screening, Fecal blood test, Colonoscopy

Core tip: It is unclear whether suboptimal screening contributes to the increased risk of cancer within families. We evaluated compliance with colon cancer screening guidelines among adults in the United States. Our study suggested that adults with a family history of any cancer had higher screening rates, but the smallest increase was noted among blacks. Overall, screening was lower among blacks and Hispanics to such an extent that screening among those with a family member with cancer was not higher than screening among whites without a family member with cancer. There is a particular need to improve screening among high risk blacks.



INTRODUCTION

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States[1]. There is ample evidence that screening reduces the burden from this deadly but largely preventable disease[2-4]. Unfortunately, screening rates are suboptimal among the population, particularly among racial/ethnic minorities.

A primary driving factor for the time to initiate CRC screening is the family history of CRC[5]. However, it is well known that malignancies of other organ sites are associated with syndromic CRC such as Lynch syndrome (hereditary non-polyposis colorectal cancer)[6,7]. Lynch syndrome is caused by mutations in mismatch repair gene and is associated with an increased the risk of CRC but other malignancies such as endometrial and urogenital cancers are associated with this syndrome as well.

We hypothesized that CRC awareness should be higher among families with any history of cancer, not just CRC. This awareness should in turn be associated with uptake of CRC screening. The burden of CRC is highest among blacks due to multiple factors related to poorer access, inadequate utilization of healthcare resources even when available and possible biological susceptibility differences[8-10]. Furthermore, blacks are less likely to be aware of cancer diagnosis of their family members[11,12]. We postulated that increased CRC incidence and mortality among blacks may be due to poorer uptake of CRC screening among those at a higher risk of the disease. The aim of the present study was to evaluate compliance with CRC screening guidelines among United States adults with and without a family member with any cancer and investigate differences in compliance by race/ethnicity (whites, blacks and Hispanics).

MATERIALS AND METHODS

We used data from the 2007 Health Information National Trends Survey (HINTS) and the details of the survey have been published[13]. In summary, HINTS was a national survey of adults on health-related information and practices. It was conducted by the National Cancer Institute, National Institutes of Health in the United States between January 2008 and May 2008. The survey is available online at http://hints.cancer.gov/docs/Instruments/HINTS%202007%20CATI%20Instrument%20(English).pdf and http://hints.cancer.gov/docs/HINTS2007FinalReport.pdf.

A total of 7674 people completed the HINTS telephone interview (n = 4092), or mailed survey (n = 3582). Respondents were asked to provide information on demographic and lifestyle factors, first degree family history of any type of cancer. They were also asked about colon cancer screening with fecal occult blood test, sigmoidoscopy or colonoscopy and when they had the tests. After obtaining approval (IRB-14-MED-28) from the Institutional Review Board of Howard University in Washington DC, we downloaded the dataset. For the present study, our analytical cohort consisted of 4232 respondents (weighted population size = 80161151) who were at least 50 years old and answered questions about their family history of cancer and CRC screening compliance.

Statistical analysis

Our primary outcome was the compliance to CRC screening guidelines defined as the uptake of fecal occult blood testing within 1 year, sigmoidoscopy within 5 years, or colonoscopy within 10 years. We compared the characteristics of respondents with and without family members with a history of cancer. We used survey weights in all analyses and Taylor series linearization was used for variance estimations. Logistic regression analysis was used to estimate OR and 95%CI for the association between family history of cancer and compliance with CRC screening guidelines. We also investigated this association by race/ethnicity. Our final models included age, sex, marital status, highest education achieved, race, health insurance status, smoking status and personal history of cancer. We calculated OR and 95%CI. Statistical analysis was performed by a qualified biostatistician using Stata® statistical software version 11.2 (College Station, Texas) for all analyses. All reported percentages were weighted.

RESULTS

The comparisons of the characteristics of respondents with and without a family history of any cancer are shown in Table 1. Overall, those with a family history were more likely to be female, unmarried, and have health insurance. However, there was no difference in the prevalence of cigarette smoking, body mass index, or personal history of cancer.

Table 1 Comparison of characteristics of respondents with and without a family history of cancer.
Family history of cancerP value
CharacteristicsNoYes
n = 1094 (27.4%)n = 3138 (72.6%)
Mean age, yr (95%CI)63.4 (62.7-64.2)63.8 (63.5-64.1)
Sex, n (%)< 0.001
Male520 (55.8)1158 (42.5)
Female574 (44.2)1980 (57.5)
Race, n (%)< 0.001
White818 (70.4)2560 (82.1)
Black107 (12.6)244 (9.6)
Hispanic92 (10.0)134 (5.2)
Other62 (6.9)123 (3.1)
Education status, n (%)0.03
Less than high school139 (19.6)287 (14.6)
High school287 (25.2)857 (28.6)
Some college/vocation297 (31.1)933 (31.7)
College graduate365 (24.1)1050 (25.2)
Marital status, n (%)0.01
Unmarried406 (32.1)1300 (37.2)
Married684 (67.9)1822 (62.8)
Insurance status, n (%)0.001
Uninsured100 (12.1)201 (7.3)
Insured983 (87.9)2886 (92.7)
Smoking status, n (%)0.31
Never499 (44.7)1472 (46.2)
Former400 (37.4)1205 (38.7)
Current179 (18.0)419 (15.1)
Body mass index in kg/m20.82
< 25363 (31.7)1047 (31.7)
25-29406 (39.0)1160 (37.8)
≥ 30316 (29.3)905 (30.5)
Personal history of cancer, n (%)0.06
No908 (87.8)2536 (85.3)
Yes185 (12.2)592 (14.7)

When compared to respondents without a family history of cancer, those who had family members with cancer were more likely to be compliant with CRC screening (64.9% vs 55.1%; OR = 1.45; 95%CI: 1.20-1.74). Among whites, those with family history of cancer had 8.2% absolute higher screening rates than whites without family history of cancer (OR = 1.45; 95%CI: 1.20-1.75; Table 2). Screening rates were generally lower among Hispanics and blacks. Blacks had the lowest increase in screening rates (5.3%) when a family member had a history of cancer which was not statistically different from blacks without a family member with cancer diagnosis (OR = 1.34; 95%CI: 0.61-2.94). Although, Hispanics had the lowest screening rates among those without history of cancer (41.9%), the absolute increase in screening rates was highest among Hispanics (14.7%) when a family member has had a history of cancer.

Table 2 Intra-racial comparison of being up-to-date with colorectal cancer screening by racial distribution of family history of any cancer.
Family history of any cancerUp-to-date with CRC screening
Wt % screenedUnadjusted OR (95%CI)Adjusted OR (95%CI)
OverallNo (n = 1094)55.1ReferenceReference
Yes (n = 3138)64.91.51 (1.25-1.81)1.45 (1.20-1.74)
By race
WhiteNo (n = 818)58.7ReferenceReference
WhiteYes (n = 2560)66.91.42 (1.18-1.72)1.49 (1.24-1.78)
BlackNo (n = 107)49.2ReferenceReference
BlackYes (n = 244)54.51.24 (0.64-2.38)1.34 (0.61-2.94)
HispanicNo (n = 92)41.9ReferenceReference
HispanicYes (n = 134)56.71.81 (0.84-3.89)1.42 (0.55-3.67)

Despite increase in CRC screening rates among blacks and Hispanics with family history of cancer, their screening rates were still numerically lower than the screening rates among whites without a family history of cancer. However, there were no statistically significant differences in the comparison of interracial screening rates (Table 3).

Table 3 Inter-racial comparison of being up-to-date with colorectal cancer screening by racial distribution of family history of any cancer.
RaceFamily history of any cancerUp-to-date with CRC screening
Wt % screenedUnadjusted OR (95%CI)Adjusted OR (95%CI)
WhiteNo (n = 818)58.7ReferenceReference
WhiteYes (n = 2560)66.91.42 (1.18-1.72)1.45 (1.21-1.74)
BlackNo (n = 107)49.20.68 (0.39-1.18)0.96 (0.51-1.80)
BlackYes (n = 244)54.50.84 (0.54-1.31)1.16 (0.71-1.90)
HispanicNo (n = 92)41.90.51 (0.27-0.95)0.84 (0.48-1.47)
HispanicYes (n = 134)56.70.92 (0.57-1.48)1.25 (0.72-2.18)
DISCUSSION

In the present study, we evaluated compliance with CRC screening guidelines among United States adults with and without a family history of cancer overall and by race/ethnicity. Irrespective of race/ethnicity, we found that those with a family history of cancer were more likely to be compliant with CRC screening guidelines compared to those without a family history. This pattern was present among each racial/ethnic group. However, this relationship was statistically significant only among whites. Among blacks, the absolute increase in the compliance with CRC screening among those with a family history of cancer was small. We found that screening rates were so low among blacks that the higher screening rates observed among blacks with family history of cancer were still numerically lower albeit not statistically different from the screening rate among whites without a family history of cancer. This suggests that the increased CRC burden among blacks may be, in part, due to low screening rates among high risk blacks and underscores the need to increase awareness and screening rates among blacks.

Although the Hispanics in this study have the lowest CRC screening rates among those without a family history of cancer, they exhibited the highest absolute increase in CRC screening among those with a family history of cancer. This suggests an appropriate response in uptake of preventive services among Hispanics, but the screening rates were still lower than that among whites without a family history of cancer. This finding indicates that increased education about CRC screening is needed among Hispanics.

We are not aware of any other study that has examined the association of a family history of any cancer with CRC screening for a direct comparison to our study. However, prior studies have examined the CRC screening among persons with a family history of CRC. Using data from the 2005 California Health Interview Survey (CHIS), Ponce et al[14] reported that screening rates were lower among Hispanics in general when compared with whites, but disparities were more pronounced among respondents with a family history of CRC (OR = 0.28; 95%CI: 0.11-0.60) as compared to disparity among those without family history of CRC (OR = 0.74; 95%CI: 0.59-0.92). However, CRC screening rate was comparable among blacks and whites among those with (OR = 0.92; 95%CI: 0.31-1.34) or without a family history of CRC (OR = 1.08; 95%CI: 0.84-1.40). In another study which used the 2009 CHIS, Almario et al[15] investigated CRC screening among respondents with a family history of CRC in California. The authors reported that there was no difference in overall screening rate among blacks when compared to whites (OR = 1.03; 95%CI: 0.81-1.27). However, among individuals who were 40-49 years old (when early screening should have started because of the increased risk of CRC), blacks were 71% less likely to have had a colonoscopy (OR = 0.29; 95%CI: 0.04-0.87). Taken together, these two studies suggest lower rates of appropriate CRC screening among blacks and Hispanics at an increased risk of CRC. However, the studies focused only on residents of the state of California. Nonetheless, these findings were comparable to our findings that are based on nationally representative data of United States adults.

It is unclear why the rates of CRC screening was lower among these minority populations, but we speculate that known factors such as health literacy, access and utilization differences may be playing important roles. In a previous study using the 2007 HINTS data, Orom et al[16] reported differences in perceived cancer risk by race. The authors reported that Hispanics were less likely to perceive themselves at higher risk of cancer even when they have family members with cancer. This disconnect may be related to health literacy or communication challenges. It is well known that blacks are less likely to discuss their chronic health problems with family members[17,18] and often hold fatalistic beliefs which negatively correlate with uptake of preventive services such as CRC screening[19].

There are some notable strengths of our study. We examined compliance with CRC screening guidelines among a nationally representative large sample of United States adults and two modes of survey was used (mail and telephone), thereby increasing the reach of the survey. Furthermore, the survey was conducted in English and Spanish to ensure broader participation. However, our study has important limitations. Although we do not suspect that respondents would have any motivation not to tell the truth, but our study was based on self reports and we could not abstract medical records to verify CRC screening uptake and the time they took place. Also, the race designation in the HINTS survey was by self-identification. Furthermore, our study did not capture other factors which may influence CRC screening compliance such as accessibility to healthcare facilities, availability of culturally sensitive care providers and type of health insurance coverage.

In conclusion, while being up-to-date with CRC screening is generally higher among those with a family history of cancer, blacks and Hispanics with a family history of cancer were less likely to be compliant with CRC screening guidelines compared with whites without a family history of cancer. There is a need to improve cancer education among blacks and Hispanics and increase CRC screening rates, especially among higher risk groups.

COMMENTS
Background

The risk of cancer is higher among families when a member has been diagnosed with cancer. The current study evaluated compliance with colorectal cancer (CRC) screening guidelines among adults with and without a family member with a history of cancer.

Research frontiers

The CRC screening rates were higher among United States adults with family members with cancer diagnosis. By race, CRC screening rates among blacks and Hispanics were lower than whites. The screening rates among blacks and Hispanics with family history of cancer did not even reach the level of screening among whites without family history of cancer.

Innovations and breakthroughs

The current study examined whether United States adults with a family history of cancer were more likely to be compliant with CRC screening guidelines. This has not been thoroughly investigated previously.

Applications

Blacks and Hispanics have lower screening rates than whites even when they have family members with history of cancer. This study suggests that the low absolute increase in CRC screening rates among blacks when a family member has a history of cancer may represent inadequate CRC screening uptake among high risk blacks. This may be playing a role in the observed CRC disparity by race in the United States.

Terminology

Screening for CRC reduces the incidence and mortality from the disease.

Peer-review

The manuscript is a well-designed observational study that addressed a major issue about health behavior among different races. The authors managed to reveal this issue through extensive research and thorough statistical analysis.

Footnotes

P- Reviewer: Harmanci O, Kouraklis G, Sam MR, Venskutonis D S- Editor: Ji FF L- Editor: A E- Editor: Liu SQ

References
1.  Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9172]  [Cited by in F6Publishing: 9815]  [Article Influence: 1090.6]  [Reference Citation Analysis (0)]
2.  Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med. 1993;328:1365-1371.  [PubMed]  [DOI]  [Cited in This Article: ]
3.  Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, Bresalier R, Andriole GL, Buys SS, Crawford ED. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345-2357.  [PubMed]  [DOI]  [Cited in This Article: ]
4.  Singh H, Nugent Z, Demers AA, Kliewer EV, Mahmud SM, Bernstein CN. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139:1128-1137.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 341]  [Cited by in F6Publishing: 363]  [Article Influence: 25.9]  [Reference Citation Analysis (0)]
5.  Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, Dash C, Giardiello FM, Glick S, Levin TR. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130-160.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1169]  [Cited by in F6Publishing: 1163]  [Article Influence: 72.7]  [Reference Citation Analysis (0)]
6.  Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348:919-932.  [PubMed]  [DOI]  [Cited in This Article: ]
7.  Vasen HF. Review article: The Lynch syndrome (hereditary nonpolyposis colorectal cancer). Aliment Pharmacol Ther. 2007;26 Suppl 2:113-126.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 50]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
8.  Laiyemo AO, Doubeni C, Pinsky PF, Doria-Rose VP, Bresalier R, Lamerato LE, Crawford ED, Kvale P, Fouad M, Hickey T. Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities. J Natl Cancer Inst. 2010;102:538-546.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 143]  [Cited by in F6Publishing: 163]  [Article Influence: 11.6]  [Reference Citation Analysis (0)]
9.  Tammana VS, Laiyemo AO. Colorectal cancer disparities: issues, controversies and solutions. World J Gastroenterol. 2014;20:869-876.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 44]  [Cited by in F6Publishing: 53]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
10.  Laiyemo AO. In search of a perfect solution to ensure that “no colon is left behind”. Dig Dis Sci. 2012;57:263-265.  [PubMed]  [DOI]  [Cited in This Article: ]
11.  Kupfer SS, McCaffrey S, Kim KE. Racial and gender disparities in hereditary colorectal cancer risk assessment: the role of family history. J Cancer Educ. 2006;21:S32-S36.  [PubMed]  [DOI]  [Cited in This Article: ]
12.  Pinsky PF, Kramer BS, Reding D, Buys S. Reported family history of cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol. 2003;157:792-799.  [PubMed]  [DOI]  [Cited in This Article: ]
13.  Cantor D, Coa K, Crystal-Mansour S, Davis T, Dipko S, Sigman R.  “Health Information National Trends Survey (HINTS) 2007: Final Report”. 2009; Available from: URL: http://hints.cancer.gov/docs/HINTS2007FinalReport.pdf.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Ponce NA, Tsui J, Knight SJ, Afable-Munsuz A, Ladabaum U, Hiatt RA, Haas JS. Disparities in cancer screening in individuals with a family history of breast or colorectal cancer. Cancer. 2012;118:1656-1663.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 25]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
15.  Almario CV, May FP, Ponce NA, Spiegel BM. Racial and Ethnic Disparities in Colonoscopic Examination of Individuals With a Family History of Colorectal Cancer. Clin Gastroenterol Hepatol. 2015;13:1487-1495.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 10]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
16.  Orom H, Kiviniemi MT, Underwood W, Ross L, Shavers VL. Perceived cancer risk: why is it lower among nonwhites than whites? Cancer Epidemiol Biomarkers Prev. 2010;19:746-754.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 68]  [Cited by in F6Publishing: 70]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
17.  Miglani S, Sood A, Shah P. Self reported attitude and behavior of young diabetics about discussing their disease. Diabetes Res Clin Pract. 2000;48:9-13.  [PubMed]  [DOI]  [Cited in This Article: ]
18.  Körner H. Negotiating cultures: disclosure of HIV-positive status among people from minority ethnic communities in Sydney. Cult Health Sex. 2007;9:137-152.  [PubMed]  [DOI]  [Cited in This Article: ]
19.  Powe BD. Fatalism among elderly African Americans. Effects on colorectal cancer screening. Cancer Nurs. 1995;18:385-392.  [PubMed]  [DOI]  [Cited in This Article: ]