Occurrence Of Multiple Primary Cancers Research Articles

Triple Primary Cancers: An Analysis of Genetic and Environmental Factors.

In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility. See related Spotlight, p. 193.

Three novel rare TP53 fusion mutations in a patient with multiple primary cancers: a case report

Abstract As survival rates improve and detection technologies advance, the occurrence of multiple primary cancers (MPCs) has been increasing. Approximately 16% of cancer survivors develop a subsequent malignancy, with lung cancer often developing after esophageal cancer due to potential “field cancerization” effects. Despite this observation, the genetic heterogeneity underlying MPCs remains understudied. However, the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition. This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs, namely, AP1M2–TP53 (A1;T11) fusion, TP53–ILF3 (T10;I13) fusion, and SLC44A2–TP53 (S5;T11) fusion. This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer, which occurred 6 years after the diagnosis of esophageal squamous cell cancer. This unique report may provide supplementary data that enhance our understanding of the genetic landscape of MPCs.

Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma.

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

180P An HLA-diet-oriented system unveiling organ-specific occurrence of multiple primary cancers (MPC) with prevention strategy: A large cohort study of 47,550 cancer patients

180P An HLA-diet-oriented system unveiling organ-specific occurrence of multiple primary cancers (MPC) with prevention strategy: A large cohort study of 47,550 cancer patients

Landscapes of synchronous multiple primary cancers detected by next-generation sequencing.

An increase in the detection rate of multiple primary cancers has been accompanied with declining cancer death rates over the past few decades. However, synchronous multiple primary tumors have gradually increased, and the molecular mechanisms involved in the synchronous occurrence of multiple primary cancers of different origins are unclear. To investigate these mechanisms, we sequenced cancer tissues by FoundationOne CDx. Data were annotated with annovar, and we then performed pathway enrichment analysis. A total of 109 genes that were mutated in all samples were clustered into different diseases, biological processes, and molecular functions. GO and KEGG analyses indicated that the P53 and PKB signaling pathways may be relevant to the occurrence of synchronous multiple primary cancers. In summary, patients with a concordance of mutations in pathogenetic genes may have a higher risk of developing a second cancer. Our research may provide a basis for the development of individualized treatments for synchronous multiple primary cancers.

Abstract P2-09-03: Pathogenic variants among female breast cancer patients with a subsequent cancer demonstrate preventable cancer burden

Abstract Background: Among females with breast cancer, multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. Herein we report the frequency of germline pathogenic/likely pathogenic variants (PVs) among females with breast cancer (BC) and primary cancer of &amp;gt;1 other site who underwent multi-gene panel testing (MGPT) through a single lab. Among females first diagnosed with BC who had a PV in an actionable gene, we quantified the frequency of subsequent breast and non-breast cancers. Among those who later developed a second BC, ovarian, endometrial or colon cancer, we determined the percentage of patients with MPCs who would have been identified as high-risk if all women had had MGPT after a first diagnosis of breast cancer. Methods: Females with breast cancer and MPCs who underwent germline genetic testing with Ambry Genetics from 3/2012 to 12/2016 were included in our cohort. Eligible individuals had multigene panel testing, which included 21 genes at minimum (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53). Clinical factors including age at diagnosis, age at testing and cancer type were obtained from test requisition forms and clinical notes. Patients with &amp;gt;1 PV were excluded from the analysis. Results: Of the 6617 patients with MPCs including BC tested for the 21 genes in the analytic cohort, most were white (70.8%), with median age at testing 63 years (IQR: 16). The median ages of first and second cancer diagnosis were 49 (IQR: 18) and 59 (IQR: 16) years, respectively. Considering the diagnostic order of BC, PV prevalence was 16.5% (444/2687) with BC as the 1st cancer diagnosis, 11.2% (296/2641) with BC as the 2nd cancer diagnosis, 15.2% (49/323) as 3rd or later diagnosis (p&amp;lt;0.001). Based on the PV identified through genetic testing, 411 of 2687 (15.3%) females with BC as a first diagnosis would have been identified as high-risk and 227 (8.4%) as eligible for altered surveillance or risk-reducing interventions for a cancer that they subsequently developed. Specifically, of the 318 (11.8%) females with a PV in ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PTEN, STK11, or TP53, 73 (23%) developed a subsequent BC. Of the 241 (9.0%) females with PVs in genes including ovarian cancer susceptibility (BRCA1, BRCA2, BRIP1, PALB2, RAD51C, or RAD51D), 143 (59.3%) developed ovarian cancer, 21 of whom also developed a second breast cancer. Among the 41 (1.5%) females with Lynch syndrome, 25 (61.0%) were later diagnosed with endometrial cancer and 10 (24.4%) were diagnosed with colorectal cancers (3 had both). Conclusions: Our data show a significant prevalence of germline PV in cancer susceptibility genes in women with MPC including BC. Further, the data suggest that a strategy testing all BC patients at diagnosis to identify actionable PV could permit the appropriate use of risk-reducing and surveillance strategies to reduce the occurrence of MPC among BC survivors. Citation Format: Brittany L. Bychkovsky, Min-Tzu Lo, Amal Yussuf, Carrie Horton, Parichehr Hemyari, Holly LaDuca, Judy E. Garber, Huma Q. Rana. Pathogenic variants among female breast cancer patients with a subsequent cancer demonstrate preventable cancer burden [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-03.

Analysis of M2 macrophage infiltration and its clinical significance in 44 patients with multiple primary cancers of the head and neck

Objective: To investigate and analyze the characteristics of M2 macrophage infiltration and the clinical significance in patients with multiple primary cancers (MPCs) of head and neck in order to explore its role in the diagnosis and prognosis for patients with MPCs. Methods: RNA-seq data were downloaded from the Genomic Data Commons data portal (TCGA) and the R software v4.0.3 was used to statistically analyze the differences. A retrospective analysis was conducted by screening the clinical data of 44 patients (17 males and 27 females) with MPCs in head and neck from July 1998 to February 2016 in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. Clinical data from a batch of 41 patients (28 males and 13 females) with gingival cancer and without MPCs from August 2013 to December 2015 were collected and analyzed. The number of CD163 positive cells and the expression patterns in immunohistochemically panoramic slices were observed under high magnification. Chi-square test and Spearman correlation analysis were used to compare the difference and correlation between the CD163 positive counts and/or depths of invasion and the number of incidences. The descriptive statistics on the clinical features was performed by SPSS 25.0. Results: TCGA database analysis showed that the infiltration of macrophage in patients with squamous cell carcinoma of head and neck (HNSCC) was increased compared to the para-cancer sites. A total of 142 tissue samples from 44 patients with MPCs were selected in the present single-center retrospective research. The number of CD163-positive cells in MPCs patients [90.9% (40/44)] was significantly increased compared to single gingival cancer patients [61.0%(25/41)] (r=0.353, P=0.001), which was related to the number of occurrence (r=0.368, P=0.001). The ratio of the CD163 counts in primary tumor to the depths of invasion was positively correlated with the number of onsets (r=0.331, P=0.03). In terms of clinical features, the 44 patients with MPCs were mainly female, non-smoking, no alcohol addiction, no systemic history, Tis-T2 stage and N0 stage squamous cell carcinoma. The number of incidences ranged from two to eight. The incidence of cancer relative to synchronous cancer increased with the increased occurrence of MPCs. The primary cancer mainly occurred in tongue, gingiva and buccal sites, while the proportion of onset sites in gingiva, buccal and palate areas increased with the increased occurrence. Conclusions: M2 type macrophage counts and/or ratio to depth of infiltration were associated with the occurrence of MPCs, which could be used as a clinical indicator to distinguish single and MPCs in HNSCC. For early stage of HNSCC, patients with clinical characters of women, non-smoking, no alcohol addiction, no systemic medical history and sites of tongue, gingiva, and buccal should be paid more attention on their follow-up plan. The findings in the present study was also helpful to explore new treatment methods for the patients with MPCs.

Investigation of multiple primary cancers in patients with bone and soft tissue primary malignancies: A retrospective, institution-based study.

In the aging society in Japan, the occurrence of multiple primary cancers has recently increased due to an increase in life expectancy and increased development in cancer diagnostic technology and improvement in treatment outcomes. However, few reports have focused on multiple primary cancers in patients with bone and soft tissue tumors. The present study aimed to analyze the clinical characteristics of patients with multiple malignancies of the bone and soft tissue. Between April 2008 and April 2017, among 973 patients treated at the Department of Orthopedic Surgery, Osaka City University Hospital, those with multiple primary cancers involving bone and soft tissue were identified. The number of cases with multiple cancers in the present study was 30/973 (3.08%), including 21 males and 9 females. The median age at diagnosis of patients with bone and soft tissue sarcoma was 73.5 years (range, 7-83 years). There were 22 patients with double cancers, and 5, 2 and 1 patients with triple, quadruple and quintuple cancers, respectively. Colorectal cancer was the most common primary cancer (n=9). In total, 28.6% of patients had simultaneous cancer, while 71.4% of patients had heterochronous cancer. The overall 5-year survival for all patients was 75.6%. The prognosis of patients with double cancer of bone and soft tissue sarcoma was not necessarily poor. However, it is necessary to pay attention to the possibility of secondary malignancy. Therefore, it is essential to be careful and well organized when selecting treatment modalities and to adopt a logistical approach for the care of patients with ongoing multiple malignancies.

Multiple primary cancers in patients with gastric cancer: A retrospective study in China National Cancer Center.

337 Background: Gastric cancer (GC) is common in China. With the total incidence of cancer keeping rising in China, the occurrence of multiple primary cancers with GC is growing. Early detection and diagnosis of second or more primary cancers are vital for patients’ survival. Methods: Patients with multiple primary cancers containing gastric adenocarcinoma treated in China National Cancer Center from January 2010 to December 2017 were included. A 6-month interval was used to separate synchronous and metachronous cancers (according to IARC/IACR criteria). Results: 479 patients met the criteria were included, with 452 (94.4%), 24 (5.0%), 3 (0.6%) patients having two, three or more primary cancer sites respectively, contributing a total of 510 cancer sites besides stomach (Table). Malignancies at 257 (50.4%) sites occurred with GC synchronously, while 253 (49.6%) occurred metachronously. The median age at the diagnosis of first cancer was 59 (interquartile range [IQR], 53-66) years. The median interval between the diagnosis of first primary cancer and metachronous second one was 50.3 (IQR, 23.7-97.0) months. Cancers outside gastrointestinal (GI) tract were more likely to occur with GC metachronously, while GI tract cancers were more likely to occur synchronously (χ²=55.36, p&lt;0.001). Out of 479 patients, there were 352 (73.6%) male and 127 (26.4%) female. The most common associated cancer was esophagus cancer (142, 40.3%) in male, and breast cancer (31, 25.4%) in female. 236 (49.8%) patients were current smokers or ex-smokers, and 190 (40.1%) were regular alcohol consumers. 110 (23.2%) had first-degree relative cancer family history, with 84 (17.7%) having GI tract cancer family history. Conclusions: GI tract including esophagus and colorectum should be carefully scrutinized during GC peri-operation period. Further genetic research is warranted to explore the potential pathogenesis of multiple primary cancers.[Table: see text]

A CASE OF LEUKEMIA COMPLICATED BY NON-SMALL CELL LUNG CANCER

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: The occurrence of multiple primary cancers (MPCs) is rare. The diagnosis and treatment of MPCs is often challenging, and often, they cannot be treated simultaneously (1). We report a case of a patient with recurrent pre-B-cell acute lymphoblastic leukemia (pBALL) who was diagnosed with a new non-small cell lung carcinoma (NSCLC). CASE PRESENTATION: A 51 year old male with a remote history of testicular cancer s/p orchiectomy and cisplatin and recurrent pBALL presented with a 4 day history of shortness of breath, non-productive cough and fatigue. Twelve months prior, he was diagnosed with pBALL and treated with 1 cycle of cytarabine, dexamethasone, vincristine, daunorubicin, pegasparagasen and intrathecal methotrexate, and 4 cycles of cyclophosphamide, vincristine, doxorubicin, and dexamethasone, which he completed 2 months prior to presentation. A CT angiogram showed a 2.4 cm right parahilar mass (Figure 1). Bronchoscopy revealed an endobronchial lesion in the right upper lobe (Figure 2) and fine needle aspiration was performed. Endobronchial ultrasound was employed to perform transbronchial fine needle aspiration of station 11R (Figure 2). Immunohistochemistry showed positive staining for CK5/6 and CKAE1/3. P53 staining was also strongly positive in the malignant cells (Figure 3). These staining patterns supported a diagnosis of NSCLC. The patient was readmitted shortly after with recurrence of his pBALL. Unfortunately, given disease progression on imaging and by symptoms, the patient opted for hospice care. DISCUSSION: The prevalence of MPCs is uncertain, ranging between 0.734-11.7%(2). While MPCs are uncommon in general, the combination of hematologic and solid cancers is rare. The SEER database suggests a slight increased occurrence of lung cancer in patients with ALL compared to the general population (3). The etiology is not clear. The few cases that have been published highlight the association between hematologic cancers treated with various chemotherapy regimens and the development of subsequent solid tumors, or a possible hereditary component (1,3). CONCLUSIONS: Although it may seem redundant to biopsy a new lesion identified in a patient with malignancy, it is important that clinicians consider the possibility of MPCs in certain clinical contexts as they can complicate primary disease treatment and may limit treatment options of the new disease. Reference #1: Cui Y, Liu T, Zhou Y, et al. “Five cases report of solid tumor synchronously with hematologic malignancy.” Cancer Res Treat. 2012 Mar;44(1):63-8. https://doi.org/10.4143/crt.2012.44.1.63. Epub 2012 Mar 31. Reference #2: Demandante CG, Troyer DA, Miles TP. “Multiple primary malignant neoplasms: case report and a comprehensive review of the literature.” Am J Clin Oncol. 2003 Feb;26(1):79-83. Review. Reference #3: Shah, B. K. (2013). Second Primary Malignancies In Adult Acute Lymphoblastic Leukemia. Blood, 122(21), 3871. Accessed March 14, 2019. Retrieved from http://www.bloodjournal.org/content/122/21/3871. DISCLOSURES: No relevant relationships by Erum Arain, source=Web Response No relevant relationships by Amit Goyal, source=Web Response No relevant relationships by Michal Reid, source=Web Response

Metachronous double primary cancer of epithelial and mesenchymal origins

Rationale:Metachronous double primary cancers from the same origin have previously been reported in several studies; however, the occurrence of double primary cancers from different tissue origins has not been reported earlier.Patient concerns:We analyzed 10 patients with requirement surgical treatment.Diagnoses:After over 6 months of the surgery, histopathological examination confirmed the presence of at least two neoplastic lesions with distinct histopathology at different locations.Interventions:These patients underwent surgery and the hematoxylin and eosin staining was performed according to standard protocol in all cases.Outcomes:Since the occurrence of multiple primary cancers is an extremely rare event, it is difficult to find a large sample size of patients with double primary cancers at one study center. All patients included in this study received surgical therapy twice and had a final tissue histopathologic diagnosis.Lessons:Based on our findings, it is concluded that a prolonged follow-up examination for cancer patients should be taken into consideration to provide early detection of secondary tumors and improve overall life expectancy of these patients. Furthermore, clinicians should be well aware of the possibility of cancer patients developing a second primary cancer of a different tissue origin.

Histologic and immunohistochemical evaluation of mirror image biopsies in oral squamous cell carcinoma

Background and objectiveThe concept of field cancerization has frequently been quoted to explain the occurrence of multiple primary cancers in the head and neck region and recurrence following complete excision of the original tumor. The main objective is to study the occurrence of field changes in mirror image biopsy in relation to histopathological changes in the oral mucosa among oral cancer patients using hematoxylin and eosin and to study the expression pattern of cytokeratin, Ki-67 and p53 in oral squamous cell carcinoma and mirror image biopsy. Materials and methodsA pilot study of 15 patients clinically diagnosed with carcinoma lesion and their corresponding mirror image sites were taken and stained using immunohistochemistry method for the expression of cytokeratin, Ki-67 and p53. ResultsPrimary tumors showed strong positive staining for cytokeratin throughout both the epithelium and malignant epithelial islands but absence of staining for Ki-67 and p53. ConclusionCK may be useful in predicting epithelial differentiation and Ki-67 and p53 act as weak indicators of malignant disease progression in oral tissues.

A case report for three different malignancies in one patient

AbstractIntroduction: The occurrence of multiple primary cancers (MPC) is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported. Case presentation: We report here a case of a 56-year-old Saudi woman attended initially to us in 2012 as a case of breast cancer with a history of renal cell carcinoma treated in 2005. Our patient was treated with surgery for renal cell carcinoma and remained in good control for 7 years, when she developed a left breast mass and by work up she was diagnosed as a case of left breast cancer which was later treated by surgery and chemotherapy, and also because of the presence of rectal thickness in her work up which was confirmed by PET-CT, she also underwent colonoscopy with biopsy which confirmed as a rectal adenocarcinoma of primary Lower GIT origin which was later treated by surgery. Conclusion: Although the association of MPC can be considered a rare occurrence, improving survival in cancer patients has made this situation more f...

Synchronous Renal and Hepatocellular Carcinomas

Summary Multiple synchronous primary tumours can cause diagnostic difficulties regarding primary origin versus metastatic spread. Greater awareness of concurrent carcinogenesis is necessary as more frequent occurrence of multiple primary cancers can be expected in future due to the growing tumour burden in the aging world population along with improved treatment efficacy. Here we report a 58-year-old male patient, who was diagnosed with two rare synchronous tumours: hepatocellular carcinoma and renal clear cell carcinoma. Both tumours were radically removed by simultaneous liver and kidney resection.

Metachronous double malignancy involving the kidney and the breast: A case report

The occurrence of multiple primary cancers is rare; it can be missed as a disease progression. The etiology remains controversial. We report a case of a 55-year-old female with metastatic renal cell carcinoma treated with sutent followed by left sided nephrectomy. Follow-up CT showed increase in the size of the right axillary lymph nodes which was proven after biopsy to be metastatic adenocarcinoma of the breast. Any suspicious disease progression in a single site not compatible with disease history should be biopsied for confirmation. The relationship between renal cell carcinoma and breast cancer is still unclear, and more case reports are required to determine this relationship.

Frequency of multiple primary cancers in the lung and other organs in hemodialysis patients

We examined whether cancers frequently occur in hemodialysis patients, and therefore, investigated the features and outcomes of hemodialysis patients who had undergone surgery for non-small cell lung cancer. Between 1995 and 2011, 14 hemodialysis patients with lung cancer (8 males and 6 females) with a mean age of 67.0years successfully underwent pulmonary resection at our institution. We investigated the 5-year survival rate and causes of death. The occurrence of multiple primary cancers in our patients and other lung-cancer patients reported in the articles were statistically compared by Chi-square test. A p value <0.05 was considered to be statistically significant. The 5-year survival rate was 47.3%, and six patients had died before our investigation. Four of the six had died of non-cancerous diseases related to hemodialysis. Five of 14 patients had a history of other primary cancers in other organs, and this incidence rate of multiple primary cancers was significantly higher than in other lung-cancer patients (p=0.0071). The frequency of cancer in hemodialysis patients can be underestimated because of their early deaths by non-cancerous diseases. However, the incidence rate of multiple primary cancers may represent a unique characteristic of such patients.

Oral field cancerization: current evidence and future perspectives

Oral field cancerization implies that oral cancer does not arise as an isolated cellular phenomenon but rather as an anaplastic tendency involving many cells at once and results in the multifocal development of cancer at various rates within the entire field in response to a carcinogen especially tobacco. This concept has been frequently used to explain the occurrence of multiple primary cancers and recurrences following complete excision of oral cancer. This review deals in detail with the origin, principle, various theories used to explain this effect and molecular, genetic, as well as cytogenetic findings related to oral field cancerization. Further, the clinical implications and future research directives are also discussed.

Triple malignancy in a single patient including a cervical carcinoma, a basal cell carcinoma of the skin and a neuroendocrine carcinoma from an unknown primary site: A case report and review of the literature

IntroductionThe occurrence of multiple primary cancers is rare. Only a few cases and patient reviews of an association of triple malignancy have been reported.Case presentationWe report here a case of a 78-year-old Moroccan woman presenting initially with a synchronous double malignancy, the first in her cervix and the second in her skin. Our patient was treated with radiation therapy for both tumors and remained in good control for 17 years, when she developed a metastatic disease from a neuroendocrine carcinoma of an unknown primary site.ConclusionsAlthough the association of multiple primary cancers can be considered a rare occurrence, improving survival in cancer patients has made this situation more frequent.

Cancer Statistics, Trends, and Multiple Primary Cancer Analyses from the Surveillance, Epidemiology, and End Results (SEER) Program

An overview of cancer statistics and trends for selected cancers and all sites combined are given based on data from the Surveillance, Epidemiology, and End Results Program. Median age at diagnosis for all sites combined shows a 2-year increase from 1974 through 1978 to 1999 through 2003. Changes in cancer incidence rates from 1975 through 2003 are summarized by annual percent change for time periods determined by joinpoint regression analysis. After initial stability (1975-1979), incidence rates in women for all cancer sites combined increased from 1979 through 2003, although the rate of increase has recently slowed. For men, initial increases in all cancer sites combined (1975-1992) are followed by decreasing incidence rates (1992-1995) and stable trends from 1995 through 2003. Female thyroid cancer shows continued increasing incidence rates from 1981 through 2003. Blacks have the highest incidence and mortality rates for men and women for all cancer sites combined. Based on 2001 through 2003 data, the likelihood of developing cancer during one's lifetime is approximately one in two for men and one in three for women. Five-year relative survival for all stages combined (1996-2002) ranges from 16% for lung to 100% for prostate cancer patients. Cancer survival varies by stage of disease and race, with lower survival in blacks compared with whites. The risk of developing subsequent multiple primary cancers varies from 1% for an initial liver primary diagnosis to 16% for initial bladder cancer primaries. The impact on the future U.S. cancer burden is estimated based on the growing and aging U.S. population. The number of new cancer patients is expected to more than double from 1.36 million in 2000 to almost 3.0 million in 2050.

The risk of subsequent primary cancers after colorectal cancer in southeast England.

Multiple cancers may occur in an individual because of a genetic predisposition, environmental exposure, cancer therapy, or immunological deficiency. Colorectal cancer is one of the most commonly diagnosed cancers, and inherited factors play an important role in its aetiology. To characterise the occurrence of multiple primary cancers in patients diagnosed with colorectal cancer and explore the possibility of a common aetiology for different cancer sites. The Thames Cancer Registry database was used to identify patients with a first colorectal cancer, resident in the North or South Thames region, diagnosed between 1 January 1961 and 31 December 1995. A total of 127 281 patients were included, 61 433 men and 65 848 women. Observed numbers of cancers occurring after the diagnosis of colorectal cancer were compared with expected numbers, calculated using appropriate age, sex, and period specific rates, to obtain standardised incidence ratios. The occurrence of colorectal cancers subsequent to cancers at other sites was also examined. Small intestinal cancer was significantly increased in men diagnosed with colorectal cancer before the age of 60 years and in women diagnosed with colorectal cancer after the age of 65 years. Colorectal cancer was also significantly increased after a first diagnosis of cancer of the small intestine. Other cancer sites with a significant increase after colorectal cancer included the cervix uteri, corpus uteri, and ovary. Patients with colorectal cancer are at increased risk of developing cancer at a number of other sites. Some of these associations are consistent with the effects of known inherited cancer susceptibility genes.