CORELLATION OF FAMILY HISTORY WITH THE PRESENCE OF CANCER IN INDOOR AND OUTDOOR PATIENTS AT ONCOLOGY DEPARTMENT, ALLIED HOSPITAL, FAISALABAD.
The subjects having a positive family history of cancer have an increased risk of many cancers. Our results point out the potential cancer syndromes seen in close relatives and this indicates that multiple cancer sites are influenced by some genetic factors. A family history of cancer among first degree relative was directly associated with increased cancer risk. Family history is a positive prognostic factor in various types of cancers.
Cancer, Family history, Genetic factors, First degree relatives, Directly associated, Positive prognostic factor.
The term “cancer” describes diseases in which abnormal cells divide controlled and invade other body tissues. Cancer cells have the ability to spread to the rest of the body through the blood and lymph systems. The commonest cancer types in males include prostate cancer, lung cancer, stomach cancer, and CRC (colorectal cancer) whereas in females, breast, lung. Cervical and colorectal cancer are commonest. Skin cancer is not part of these statistics, which if included would account for at least 40% of cases. In children ALL (acute lymphoblastic leukemia) and tumors of brain are most common, except for Africa where in children, non-Hodgkin lymphoma is seen more often.
Cancer can be grouped into broader categories. The main categories include: “Carcinoma cancer” that is present in skin or in tissues lining the internal organs. Carcinomas have further subtypes, namely adenocarcinoma, squamous cell carcinoma, basal cell carcinoma, and transitional cell carcinoma. “Sarcoma” starts in cartilage, fat, muscle, blood vessels, bone or any other connective tissue. “Leukemia” is the cancer that begins in tissue where blood is formed, such as bone marrow, and leads to large numbers of abnormal blood cell production that enter the blood. “Lymphoma and myeloma” begin in the cells that are part of immune system. “Central nervous system cancers” are those beginning in the brain tissue and spinal cord.
Triggering factors for above mentioned cancers include diet, chemicals, physical factors, ionizing radiations, hormones and hereditary factors. The risk of developing cancer become higher significantly with increasing age. In developed countries, some cancers are seen more commonly now, the reason being that due to improved health care and changes in lifestyle, more people reach old age. The financial cost for managing cancer was estimated $1.16 trillion per year in US Dollars in the year 2010.
The purpose behind this study was to figure out an association among the occurrence of commonly seen cancers and the patient’s family history of cancers. Previous literature has worked extensively with exogenous factors such as occupational exposures, ionizing radiations and smoking, correlating them to the presence of cancer. The objective of this study is to find a link between hereditary factors or family history and the development of cancer in patients.1
Family history has always been a core tool in all fields of medical practice. A person’s family history reflects the combined influences of genetics, behaviors and environmental exposures within families. 2
A large number of reports demonstrate that a positive family history is a significant risk factor in cases of chronic diseases of clinical importance including diabetes mellitus, cardiovascular diseases, stroke and several cancers. 3
Genetic information is a source of identifying people having a higher risk of developing cancer. Genetic information is provided by biological samples of DNA, family history of related diseases, medical records and findings from physical examination. The proportion of individuals carrying a mutation who will manifest the disease is called penetrance. In general, common genetic variants linked with cancer susceptibility have a lower penetrance compared to rare genetic variants. 4
An individual’s first degree relative shares half of the genes with the individual. Any relative who is two meiosis distant from an individual in a pedigree, further defined as a relative with whom one-quarter of an individual’s genes is shared (i.e. grandparent, grandchild, uncle, aunt, nephew, niece, half-siblings) 5
1. To study the statistical correlation between cancer development and the presence of positive family history
2. To study the types of cancers most frequently linked to a positive family history
REVIEW OF LITERATURE
Colorectal cancer results from both the genetic and environmental factors and their interaction. The dominant risk factor for some individuals; however, environmental factors (including diet, exercise, smoking, and obesity) are stronger risk factors in most people. 6
A family history of CRC is generally common among population. In the United States, about 5 percent of adults (aged 20 to 79 years) reported that they have a first or second-degree relative diagnosed with colorectal cancer7. Some other countries have reported somewhat higher rates, including a study from the Netherlands which reported that in adults from ages 30 to 70, 11.7% had at least one relative (first degree) with CRC. There is an increment in these rates with increasing age, suggesting that there is an increasing chance in older age groups. 8
Many studies describe the increased risk of CRC in individuals who have first-degree relatives suffering from gastrointestinal adenomas. However, these studies might have accidentally calculated the reverse risk, that is, the risk of having adenomas in relatives of CRC patients. A single study was done, carrying out colonoscopies in first-degree relatives of individuals having large adenomas, and found these people to have an elevated risk of having large adenomas or cancer. 9
There is 70% more chance of having head and neck cancer if an individual has a positive family history for it. The risk is also higher in people with a family history of other cancers that are tobacco-related. Among tobacco users and alcoholics, the risk of head and neck cancer development is 7 times higher in case of a first degree relative with head and neck cancer, than those without. This concludes that not only environmental factors and lifestyle play their role in risk but there are also genetic risk factors. 10
Carriers of BRCA1 and BRCA2 mutations have a greater risk of developing breast cancer, as compared to the general population of every age group. There is a 45 to 65% chance of development of breast cancer in carriers of BRCA1 and BRCA2 mutations, by the age of 70. A cohort study was carried out in UK on a small scale, which showed that even in women who don’t carry BRCA 1/2 mutations, but have a first degree relative who is a carrier, may have higher risk of breast CA. Higher levels of sex hormones in women with BRCA mutations may explain the higher risks.
Family history, lifestyle factors and previous breast cancer are some of the factors that may modify BRCA mutation.
The mutations of BRCA1 and BRCA2 are rare, however, this varies by ethnicity or country of origin of the patient. They affect about 0.11% and 0.12% of the general population (respectively), i.e. around 1 out of 450 women being a carrier. This means that, overall, BRCA 1 and 2 mutations in total account for approximately 2% of all breast cancers. However, 15 to 20 % of the cases in which first degree family history is positive can be explained by this. For individuals who meet the eligibility criteria related to family history is available. 11
However, on the contrary, there are many women with a positive family history of cancer of breast, but they are not found to have a significantly increased risk, at most the lifetime risk is doubled. Only 1-2% of cases of breast cancer are caused by the inheriting an autosomal dominant, high-penetrance gene, conferring up to an 85% lifetime risk of breast cancer. In some families, there is also a high risk of ovarian cancer. Features of the family history that suggest cancer may be caused by such a high-penetrance gene. 12
History of cancer in general, and in particular that of head and neck, among fathers, were associated with slightly raised risk of oral cavity cancer, but these results were not statistically significant (OR 1.3, 95% CI 0.9-1.6, and 1.5, 95% CI 0.9-2.4, respectively).
History of cancer of head and neck among mothers was significantly associated with a higher risk of cancer of oral cavity (OR 5.2, 95% CI 1.2-23.9). This OR was greater than the OR observed for fathers. History of head and neck cancer among siblings was associated with an increased risk of oral cavity cancer (OR 2.3, 95% CI 1.2-4.2). Analysis done according to type (gender) of sibling indicated a significantly higher risk among subjects having only brothers with a positive history (OR 2.6, 95% CI 1.2-5.8); history of cancer of head and neck among sisters was not significantly related with an amplified risk of oral cavity cancer (OR 1.7, 95% CI 0.6-4.2).
When the relationship between history of cancer among first-degree relatives and risk of cancer of oral cavity was analyzed, a significant association for head and neck cancer history was observed (OR 1.9, 95% CI 1.2-2.8). Oral cavity cancer risk was increased slightly by a family history of any type of cancer, but the results found were not significant statistically (OR 1.2, 95% CI 0.9-1.5), and the risk increased with increasing number of family members having any cancer. A risk of cancer of oral cavity was found to be significantly increased in individuals having a positive family history of oral cavity cancer (OR 3.5, 95% CI 1.1-11.2) and that of “head and neck cancer” (OR 1.8, 95% CI 1.1-2.9). A family history of pharyngeal, sino-nasal and laryngeal cancer was not associated with significantly higher risks of cancers of oral cavity (OR 4.6, 95% CI 0.5-44.8 pharyngeal cancer history; 1.6, 95% CI 0.6-4.4 laryngeal cancer history; and 1.7, 95% CI 0.3-8.8 sino-nasal cancer history). However, in first degree relatives of some subjects, specific locations of cancers were mentioned (26 cases of oral cavity, 5 of pharynx, 35 of larynx, and 11 cases of nasal cavity and nasal sinuses cancer). 13
The risk of oral cancer for individuals having history of oral/laryngeal or pharyngeal cancers in two or more than two first degree relatives was found 7.1 (95% CI, 1.3-37.2). A positive family history of melanoma (OR = 5.8; 95% CI, 1.3-26.4) as well as lung cancer (OR = 1.4; 95% CI, 1.0-2.0) showed a significantly higher risk. Risk of pharyngeal and oral cancer is strongly determined by a history of oral, pharyngeal and laryngeal cancer, independent of use of tobacco or alcohol. 14
Most adrenal cancers are not found to be influenced by hereditary factors, but are instead related to some syndromes, such as Li-Fraumeni syndrome, Multiple endocrine neoplasia (MEN-1), Beckwith-Wiedemann syndrome and Familial adenomatous polyposis (FAP) 15
The cause of most adrenal cortical carcinomas is not known. However, people with certain hereditary conditions, such as Multiple Endocrine Neoplasia Type 2, Li-Fraumeni syndrome, Von Hippel-Lindau syndrome, Neurofibromatosis Type 1, and Carney Complex, have a higher risk of developing an adrenal gland tumor. People having a family history of adrenal gland tumor have a risk of developing the same tumor and therefore should undergo examination and evaluation by doctor annually. 16
MATERIAL AND METHOD
Cross sectional study
All patients coming to OPD and Indoor of oncology Department, Allied hospital, Faisalabad.
Duration of study:
24th July 2014 to 24th August 2014.
Place of study:
Oncology Department, Allied hospital, Faisalabad.
Non probability, convenient sampling
Size of sample:
Data collection procedure:
Questionnaire, face to face interview after taking informed consent
Data analysis procedure:
SSPS version 20
I have taken informed consent.
Figure 3: Graph showing prevalence of cancer in different age groups of patients
Figure 4: Pie Chart showing most common types of cancer in males
Figure 5: Graphical presentation of prevalence of different cancer types found in female patients
From this study it was inferred that most of the cancers have no genetic component to it, on the contrary most cancers are caused by exogenous environment factors. Family history alone is a weak determinant of cancer, but if environmental factors add up to it the chances are increased.
This study indicates that after environment related and exogenous factors, the major risk factor for cancer development is the presence of disease in the family with preponderance in those with first degree relatives having the disease.
The cancers most frequently found to have a positive family history were: colorectal 2/40 (5 %), oral cavity 2/40 (5%) , breast 1/40 (2.5%), bladder cancer 1/40 ( 2.5) , adrenal 1/40 (2.5%).
In this study of a sample population of 40 patients,of whom 19 were female and 21 were males. It was found that in females the most common type of was cancer breast with 8 patients out of 19 females studied ,ie 42 % suffering from it, followed by colorectal 11 % ,ovarian 11 %, leukaemia 11 %, larynx 5% , adrenal 5 %, oesophagus 5 %, adenocarcinoma 5 %, oral 5 %
These findings are closely correlated with the latest statistics by American Cancer Society, according to which the most common type of cancer in women is Breast (32%) , colorectal (13%) , ovarian (4%),leukaemia (6%) , Cancer larynx (2%) , adrenal ( 2%) , oesophagus (4%) and oral (2%).
In the male population the break down was as follows : The most common cancers in males were found to be:
Colorectal(20%), Oesophagus(15%), Tongue(10%), Lungs(10%), Hepatocellular(10%), Brain(10%), Non-Hodgkins(5%), Anal(5%), Bladder(5%), Larynx(5 %), Osteosarcoma(5%).
The sample population was a small one. Study can be biased due to non probability sampling. A few patients were not aware of their family history. Factors other than family history were not probed in the study.
17.5 % have a positive family history of which, 70 % have no family history of cancer and 12.5 % do not know of their family history.
1. Talking Glossary of Genetic Terms from the National Human Genome Research Institute
2. Yoon PW, Scheuner MT, Peterson-Oehlke KL. et al. Can family history be used as a tool for public health and preventive medicine? Genetic medicine. 2002;(4):304_10. Pubmed
3. Hariri S, Yoon PW, Moonesinghe R. et al. Evaluation of family history as a risk factor and screening tool for detecting undiagnosed diabetes in a nationally representative survey population. Genet Med. 2006;8(12):752-9. PubMed
4. Lindor NM, McMaster ML, Lindor CJ, et al.: Concise handbook of familial cancer susceptibility syndromes – second edition. J Natl Cancer Inst Monoger (38): 1 -93, 2008. PubMed Abstract
5. Definition from: GeneReviews from the University of Washington And The National Centre For Biotechnology Information Lister Hill National Centre for Biomedical Communication U.S National Library of Medicine, National Institutes of Health
6. GeneReviews from: the University of Washington and the National Center for Biotechnology Information
7. GeneReviews from: the University of Washington and the National Center for Biotechnology Information
8. Little J, Faivre J. Family history, metabolic gene polymorphism, diet and risk of colorectal cancer. Eur J Cancer Prev 1999; 8 Suppl 1:S61.
9. Potter JD. Colorectal cancer: molecules and populations. J Natl Cancer Inst 1999; 91:916.
10. Ramsey SD, Yoon P, Moonesinghe R, Khoury MJ. Population-based study of the prevalence of family history of cancer: implications for cancer screening and prevention. Genet Med 2006; 8:571.
11. Wilschut JA, Steyerberg EW, van Leerdam ME, et al. How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer? Cancer 2011; 117:4166.
12. Cottet V, Pariente A, Nalet B et al. Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors. Gastroenterology 2007;133:1086–92.
13. Cancer research UK (http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/riskfactors/breast-cancer-risk-factors#Family)
Annexure 1: Questionnaire
Telephone no.: _______________________________________
5000-10,000, 10,000-20,000, 20,000-30,000
Which type of cancer you have?
What was your age at diagnosis?
Is any member of your family has history of cancer?
Yes, no, don’t know
What is your relationship to that member?
First degree, second degree, third degree
Family history (first degree relatives):
Type of cancer Age at diagnosis Current age
Annexure 2: Consent form
You have been selected for this research study being conducted by Department of Community Medicine, PMC, Faisalabad. This study is only for the research purpose and your name and address will be kept confidential. Your participation is voluntary.
Signed by the interviewer: ______________________
Signed by the participant: ______________________
Annexure 3: Gantt’s chart
Durations 10 days 20 days 30 days 40 days
Data collection 7
analysis 8 – 20
Data compilation 21-35