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Year : 2019  |  Volume : 15  |  Issue : 1  |  Page : 87-91

Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran

1 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Center of Excellent for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

Date of Web Publication13-Mar-2019

Correspondence Address:
Prof. Mohammad Hossein Somi
Golgasht St., Imam Reza Hospital, Tabriz
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_421_17

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 > Abstract 

Context: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder. Colorectal cancer (CRC) has been implicated as the most common cause of death in FAP patients, especially in those with coexisting CRC at initial diagnosis (FAP-CRC).
Aim: We aimed to determine the survival rate of FAP-CRC and the factors affecting FAP-CRC survival.
Setting and Design: This was a retrospective cohort FAP study conducted in northwest Iran.
Subjects and Methods: From 2006 to 2016, 51 FAP-CRC individuals were selected from among 4588 CRC patients.
Statistical Analysis: A Student's t-test, life table method, log-rank tests, a Kaplan–Maier survival curve, and Cox regression analysis were performed and a value of P < 0.05 was set as statistically significant.
Results: A total of 51 FAP-CRC patients were selected, (30 males and 21 females), with a mean age of 42.2 years at diagnosis. The most common presenting symptom was abdominal pain and the most common primary tumor site was the rectum. The 1-, 5- and 10-year overall survival rates were 76%, 59%, and 52%, respectively. Factors affecting the FAP-CRC survival rate, namely, sex, age at CRC diagnosis, and extracolonic manifestations showed no significant differences. The difference in 5-year survival rates between patients with colon and rectal cancers was significant (75% vs. 33%, P = 0.02). The survival rate was significantly higher among patients with disease Stages I and II than those in disease Stages III and IV (P = 0.001). 5-year survival rates in patients with ileal pouch-anal anastomosis and ileorectal anastomosis were 71% and 78%, respectively (P = 0.001). There was an interesting difference in survival between FAP and attenuated FAP (P = 0.01). In cox regression analysis, distant metastasis was a significant predictor of survival (P = 0.001).
Conclusions: Long-term survival from FAP-CRC remains poor; therefore, early-stage detection and the choice of an appropriate surgical method can improve survival in such patients.

Keywords: Colorectal cancer, familial adenomatous polyposis, Iran, survival

How to cite this article:
Mirinezhad SK, Moaddab SY, Bonyadi MJ, Shirmohammadi M, Eftekharsadat AT, Somi MH. Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran. J Can Res Ther 2019;15:87-91

How to cite this URL:
Mirinezhad SK, Moaddab SY, Bonyadi MJ, Shirmohammadi M, Eftekharsadat AT, Somi MH. Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran. J Can Res Ther [serial online] 2019 [cited 2020 Apr 5];15:87-91. Available from: http://www.cancerjournal.net/text.asp?2019/15/1/87/244216

 > Introduction Top

Colorectal cancer (CRC) is the second-leading cause of cancer deaths in the USA.[1] Familial adenomatous polyposis (FAP) is an autosomal dominant inherited polyposis syndrome. In the classic form of FAP, hundreds or thousands of polyps begins at a person's colon and rectum in their second or third decade of life.[2],[3] FAP is a complex systemic disease as extracolonic manifestation (ECM) that may involve three germinative layers from ectoderm (retinal lesions, skin cysts, central nervous and endocrine tumors), endoderm (gastric, hepatic tumor, small bowel, and biliary adenomas and adenocarcinomas) and mesoderm (dental abnormalities, osteomas, and desmoids tumors).[4],[5] FAP identification is important because of the very high lifetime risk of CRC, for this reason, patients should be managed with prophylactic colectomy.[6],[7] Attenuated FAP s (AFAP), a later age at diagnosis than classical FAP, is manifested by fewer polyps, and CRC tends to occur at a later age.[2],[8] CRC has been implicated as the most cause of death in FAP patients, especially in those with coexisting CRC at initial diagnosis.[9],[10]

 > Subjects and Methods Top

This study was performed in liver and gastrointestinal disease research center, of medical sciences. All of patients registered with FAP registry system during 2006–2016, who were diagnosed to have CRC (1.1%) were enrolled. The diagnosis was confirmed by history, clinical examination, and histopathological assessment from 4588 patients with CRC.

Clinical diagnosis of FAP was made either by having over 100 colorectal adenoma/villous polyps (classic type) or by having over 10 colorectal adenoma/villous polyps and have autosomal dominant pattern in pedigree (attenuated type).

The midgut and hindgut eventually developed into right- and left-side (plus rectum) large bowel, respectively. The right side was defined as from the cecum to the proximal two-thirds of the transverse colon, whereas the left side was defined as splenic flexure to the sigmoid colon. The rectum was defined as the rectosigmoid junction and rectum.[11]

Pathological staging was graded to the American Joint Committee on Cancer (AJCC) TNM classification.[12] Survival times were computed using the date of CRC diagnosis and date of death or the end of this study.

SPSS statistical package (version 16.0; SPSS, Chicago, IL, USA) was used to complete the analyses. The age difference between FAP and AFAP were compared by Student's t-test. Life table method was used to estimate survival rates and the log-rank test in the Kaplan–Maier was used to analyses differences between the groups. A multivariate analysis of the factors that impact survival was performed using the Cox proportional hazards regression model. P < 0.05 was considered statistically significant.

 > Results Top

A total of 51 FAP patients with coexisting CRC were selected. This sample group included 30 males (58.8%) and 21 females (41.2%). The mean age at the onset of symptoms was 38.8 years (range, 13–68 years) and at CRC diagnosis, the mean age was 42.2 years (range, 14–70 years), being lower in FAP when compared to AFAP (P < 0.05) [Table 1].
Table 1: Patient's mean age at beginning of symptoms and mean age at diagnosis colorectal cancer

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The most common symptoms reported were abdominal pain (43%), intestinal bleeding (37%), change in bowel habits (12%), and weight loss (8%). The most common sites of primary tumors were the rectum (33.3%) and the sigmoid colon (25.5%).

Adenocarcinoma was identified in all of the histology reports and most grades were well differentiated (66.7%). Common sites of metastasis were the liver (40%), lungs (15%), and the brain (10%). Patients with more than two metastatic sites represented 28.6% of the study population. In the present study, 28 ECMs were detected in 21 (41.2%) patients with FAP-CRC. The most common manifestations were related to the endoderm (42.9%), including fundus polyposis (n = 4), gastroduodenal adenomas (n = 3), stomach cancer (n = 2), and small bowel cancer (n = 2).

From the total of 51 FAP-CRC patients, 21 (41.2%) patients died and 30 (58.8%) patients remained alive throughout the study period. The median follow-up time was 28 months (range, 2.2–174.3 months), and the 1-, 5-, and 10-year overall survival rates were 76%, 59%, and 52%, respectively.

Univariate analysis

Univariate analyses of the clinical characteristics and pathologic variables of patients as predictive factors are summarized in [Table 2], and the findings were as follows: sex, age at CRC diagnosis and ECM did not show significant differences in relation to survival rate (P > 0.05). The difference in 5-year survival rates between patients with colon and rectal cancer was significant (75% vs. 33%, P = 0.02). In terms of tumor differentiation, regional lymph node involvement and distant metastasis also showed significant differences in survival rate (P < 0.05). When disease stage analysis was stratified, the survival rate was significantly higher among patients with disease Stages I and II than Stages III and IV (P = 0.001).
Table 2: Univariate analysis of prognostic factors in familial adenomatous polyposis developed to colorectal cancer

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The 5-year survival in patients with ileal pouch-anal anastomosis (IPAA) and ileorectal anastomosis (IRA) was 71% and 78%, respectively (P = 0.001) [Figure 1]. According to Univariate analysis, there was an interesting difference in survival between FAP an AFAP (P = 0.01) [Figure 2].
Figure 1: Five-year survival curve comparing ileal pouch-anal anastomosis and ileorectal anastomosis

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Figure 2: Five-year survival curve comparing familial adenomatous polyposis and attenuated familial adenomatous polyposis

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Multivariate analysis

In a Cox regression analysis, distant metastasis (P = 0.001) was identified as a significant predictor of survival. Lymph node involvement (P = 0.86), stage of tumor (P = 0.07), surgical methods (P = 0.18), or variants of FAP (P = 0.11) were not identified as significant predictors [Table 3].
Table 3: Multivariate analysis, cox regression model

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 > Discussion Top

This study was undertaken to identify prognostic factors for the survival rate of FAP patients with coexisting CRC for the first time in an Iranian population. Our results indicated the significant role of surgical procedures and the existence of distant metastasis in terms of survival rates for these patients. A significant difference exists between survival rates of FAP and AFAP patients.

The development of many FAP international registries helps to reduce CRC incidence and improve patient survival.[13],[14] The adenomatous nature and multiplicity of polyps are responsible for the risk of cancer in nontreated patients, as CRC may develop 10–15 years after the polyps appear (at approximately 35 years of age) and cause death at the beginning of the fourth decade.[15],[16] According to our results, FAP accounted for approximately 1.1% of all cases of CRC (51 of 4588), and these results are in line with the national registries report.[17]

In this study, approximately 55.4% of FAP patients (51 of 92) had previously been diagnosed with CRC at the time of enrollment in the study. Inoue et al.[18] reported similar findings where 172 of 303 FAP patients (56.8%) showed CRC at the first diagnosis.

The 5-year survival rate in our study was 59%, which is higher than the rate found in a similar Italian study of 54.4%.[19] Inoue et al.[18] reported even higher rates (88.8%). In contrast, studies in Iran conducted on patients with sporadic CRC showed that the 5-year survival rate was 41% and 56.4%, respectively.[20],[21] which is less than the survival rate of FAP-CRC patients in the present study. This may be due to the different clinical pathological characteristics of neoplasia and to genetic alterations.[21]

Studies have aimed to determine patient-related factors affecting survival. Our results indicated no effect of age and sex on survival rates. This finding is consistent with previous studies.[21] Many studies report that tumor location affects the prognosis of CRC,[18],[19] which is similar to our study, where we report a lower survival rate in patients with rectal involvement.

As expected, the grade of tumor, lymph node involvement, and the disease stage had an influence on patient survival. According to AJCC stages, the 5-year survival rate for FAP-CRC Stage 1 patients was 100%, while it was 79% for Stage II patients and 68% for stage III patients. We were unable to estimate the survival rate for patients in Stage IV. When compared to a Japanese study, the 5-year patient survival rate for Stage 1 FAP-CRC was 100%, which was similar to our study, reporting 89.8% for Stage II, 87.9% for Stage III, and 48.4% for Stage IV patients.[18] The present study showed a lower survival rate for Iranian patients in Stages II–IV. This may be due to the mean age of CRC diagnosis being higher than in the Japanese study (42.2 years compared to 37.7 years). Moreover, most of our patients were probands compared to 85.5% of patients in the Japanese study.[18]

IPAA is usually the preferred first surgical option in FAP patients without cancer;[22],[23] but results remain inconsistent for patients with coexisting cancer.[24] Consistent with the findings of our study, Iwama et al.[10] showed improved 5-year survival IRA results compared to IPAA procedures. The present study showed that the 5-survival rate of AFAP patients (82%) was higher than that of the FAP patients (46%) (P = 0.01).

To the best of our knowledge, there is little information about the life expectancy of FAP and AFAP patients with coexisting CRC. Since the clinical manifestation of AFAP with coexisting CRC is similar to hereditary nonpolyposis colorectal cancer,[25] the 5-year survival rates (82% and 82.5%) for both cancer groups were again similar.[21]

The incidence of ECM in our sample was 41%, which is consistent with that in a previous study (40%).[4] In contrast to previous studies, ECM did not affect the survival rate in this study.[4],[26]

This study had some limitations. We did not perform a genetic analysis of APC and MUTYH, because of a lack of adequate funding. As AFAP and MUTYH are autosomal dominant and autosomal recessive, respectively, the risk of false-positive diagnosis was reduced with genetic counseling and family history information.

 > Conclusions Top

This study showed that the long-term survival rate of FAP with coexisting CRC remains poor. Survival from AFAP-CRC is better than that from FAP-CRC, and the incidence of CRC before being registered with FAP remains high. We believe that early stage detection and the choice of an appropriate surgical method can improve survival in such patients.


The authors wish to thank Professor Ziad Alizadeh, who kindly gave his suggestion on study design.

Financial support and sponsorship

This study was financially supported by Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Conflicts of interest

There are no conflicts of interest.

 > References Top

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American Cancer Society. Colorectal Cancer Facts & Figures 2017-2019. Atlanta: American Cancer Society; 2017. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf. [Last. [Last accessed on 2018 Apr 25].  Back to cited text no. 2
Cruz-Correa M, Giardiello FM. Familial adenomatous polyposis. Gastrointest Endosc 2003;58:885-94.  Back to cited text no. 3
Campos FG, Habr-Gama A, Kiss DR, Atuí FC, Katayama F, Gama-Rodrigues J, et al. Extracolonic manifestations of familial adenomatous polyposis: Incidence and impact on the disease outcome. Arq Gastroenterol 2003;40:92-8.  Back to cited text no. 4
Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol 2008;15:2439-50.  Back to cited text no. 5
Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med 2005;56:539-54.  Back to cited text no. 6
de Campos FG, Nicácio De Freitas I, Imperiale AR, Seid VE, Perez RO, Nahas SC, et al. Colorectal cancer in familial adenomatous polyposis: Are there clinical predictive factors?. Cir Esp 2010;88:390-7.  Back to cited text no. 7
Knudsen AL, Bisgaard ML, Bülow S. Attenuated familial adenomatous polyposis (AFAP). A review of the literature. Fam Cancer 2003;2:43-55.  Back to cited text no. 8
Belchetz LA, Berk T, Bapat BV, Cohen Z, Gallinger S. Changing causes of mortality in patients with familial adenomatous polyposis. Dis Colon Rectum 1996;39:384-7.  Back to cited text no. 9
Iwama T, Tamura K, Morita T, Hirai T, Hasegawa H, Koizumi K, et al. Aclinical overview of familial adenomatous polyposis derived from the database of the polyposis registry of Japan. Int J Clin Oncol 2004;9:308-16.  Back to cited text no. 10
Richman S, Adlard J. Left and right sided large bowel cancer – Have significant genetic differences in addition to well-known clinical differences. Br Med J 2002;324:931-2.  Back to cited text no. 11
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Barrow P, Khan M, Lalloo F, Evans DG, Hill J. Systematic review of the impact of registration and screening on colorectal cancer incidence and mortality in familial adenomatous polyposis and lynch syndrome. Br J Surg 2013;100:1719-31.  Back to cited text no. 13
Koskenvuo L, Pitkäniemi J, Rantanen M, Lepistö A. Impact of screening on survival in familial adenomatous polyposis. J Clin Gastroenterol 2016;50:40-4.  Back to cited text no. 14
Bülow S. Clinical features in familial polyposis coli. Results of the Danish polyposis register. Dis Colon Rectum 1986;29:102-7.  Back to cited text no. 15
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Vasen HF, Möslein G, Alonso A, Aretz S, Bernstein I, Bertario L, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 2008;57:704-13.  Back to cited text no. 17
Inoue Y, Ishida H, Ueno H, Kobayashi H, Yamaguchi T, Konishi T, et al. Therapeutic approaches for patients with coexisting familial adenomatous polyposis and colorectal cancer. Jpn J Clin Oncol 2016;46:819-24.  Back to cited text no. 18
Bertario L, Russo A, Sala P, Eboli M, Radice P, Presciuttini S, et al. Survival of patients with hereditary colorectal cancer: Comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer. Int J Cancer 1999;80:183-7.  Back to cited text no. 19
Moradi A, Khayamzadeh M, Guya M, Mirzaei HR, Salmanian R, Rakhsha A, et al. Survival of colorectal cancer in Iran. Asian Pac J Cancer Prev 2009;10:583-6.  Back to cited text no. 20
Haghighi MM, Vahedi M, Mohebbi SR, Pourhoseingholi MA, Fatemi SR, Zali MR, et al. Comparison of survival between patients with hereditary non polyposis colorectal cancer (HNPCC) and sporadic colorectal cancer. Asian Pac J Cancer Prev 2009;10:209-12.  Back to cited text no. 21
Ziv Y, Church JM, Oakley JR, McGannon E, Schroeder TK, Fazio VF, et al. Results after restorative proctocolectomy and ileal pouch-anal anastomosis in patients with familial adenomatous polyposis and coexisting colorectal cancer. Br J Surg 1996;83:1578-80.  Back to cited text no. 22
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Kayaalp C, Işik S, Akbaba S, Neşşar G, Oymaci E, Seven C, et al. Restorative proctocolectomy for familial adenomatous polyposis coexisting with colorectal cancer. Turk J Gastroenterol 2005;16:44-7.  Back to cited text no. 24
Cao Y, Pieretti M, Marshall J, Khattar NH, Chen B, Kam-Morgan L, et al. Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: Case report with review of the literature. Am J Gastroenterol 2002;97:1822-7.  Back to cited text no. 25
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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