Determinants of non-Hodgkin’s lymphoma at Felegehiwot specialized hospital, North West Ethiopia: A case-control study

Background The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors. Hence, the purpose of this study was to identify determinants of Non-Hodgkin lymphoma cancer among individuals who diagnosed at the Felegehiwot specialized hospital, North West Ethiopia, 2019. Methods An institution-based unmatched case-control study was conducted at the Felegehiwot Specialized hospital from December 2018 up to June 2019. The sample size calculated using the two-population proportion formula. The final sample size was 486, (162 cases and 324 controls). The simple random sampling method was employed to catch up with the estimated samples. The collected data entered into the Epi-data version 3.1 software and analyzed using SPSS version 21 software. Descriptive statistics computed. Simple logistic analysis was run (at 95% CI and p-value < 0.05) to identify the determinants of non-Hodgkin’s lymphoma. Result A total of 486 patients participated. Nearly one-third of the cases and controls were in the age group of 46–60 years. About 90% of cases and 91% of controls were orthodox Christian. Monthly income of ≤28 dollars (AOR = 2. 73, 95%CI: 1. 8, 4.2), male sex (AOR = 1. 8, 95%CI: 1.2, 2.8), ever had chemical exposure, (AOR = 11. 9, 95%CI: 7.6, 18.8), no regular physical exercise (AOR = 15. 5, 95%CI: 5.7, 42.3), and having hypertension [AOR = 0. 03; 95%CI:0.005, 0.2), lung disease (AOR = 0. 2; 95%CI: 0.06, 0.7), and chronic kidney and cardiac diseases (AOR = 0. 06; 95%CI: 0.01, 0.2) were the determinants of non-Hodgkin’s lymphoma. Conclusions The findings in this study suggest that having a low monthly income, being male sex, ever had chemical exposure, not engaged in regular physical exercise, and being diabetic were the determinants of non-Hodgkin’s lymphoma.

In Africa, approximately 300, 000 cases of non-Hodgkin lymphoma (NHL) occur each year and these infections are among the top ten causes of cancer in this continent region [6]. In Ethiopia, studies showed that there are more than 150,000 cancer cases per year [2]. Although, it appears to vary markedly throughout the region and is different among children and adults [6].
Lifestyle-related risk factors such as body weight, physical activity, diet, and tobacco use play a major role in developing NHL [7]. Thus, identifying the risk factors for NHLmay improve our understanding of the disease and isof very crucial for policymakers and program implementers at national as well as regional levels to design evidence-based intervention strategies to give emphasis and tackle the risk factors of NHL.

Study Design
An institution-based unmatched case-control study was conducted from November 2018 up to June 2019 at Felegehiwot specialized referral hospital. The hospital is located in Bahir Dar city, Amhara regional state, which is 564 km apart from Addis Ababa, the capital city of Ethiopia. The hospital is comprised of different service delivery departments. The oncology department is established in 2017. Since then, 169 patients were registered in the logbook.

Sample size determination
To determine the sample size, Epi-Info version 7 software were used by considering 95% CI, 80% Power with 1:2 case to control ratio. Then, the nal sample size was 486. (Table 1 Sampling procedure Cases: All 169 NHL patients who are on follow-up inthe oncology departmentwere scrutinized for cancer histopathological con rmation; and then, 162 NHL cases were con rmed.
Controls: Chronically ill medical patients who were on follow-up and had non-cancerous pathology resultattached to their charts in the medical department were the controls. Twounmatched controls for each case were takenby systematic sampling technique from the list of the service delivery logbook.

Exclusion criteria
Cases: the nine histo-pathologically non-con rmed patients and not on follow up in the oncology department of the hospital wereexcluded.
Control:non-cancerous,chronically ill medicalpatients,who had not pathology resultattached to their charts and who were not on follow-upin the medical departmentof the hospitalwere excluded.

Data collection and analysis
A pre-tested and structured questionnaire was used to collect data adopted from a variety of literature. Patientsociodemographic characteristics, nutritional status, and exposure to carcinogenic chemical exposure relating characteristics were collected from patient service delivery record book.Two clinical nurses and one supervisor were involved in the data collection process. Two days of rigorous training was given on how to select study participants and review medical documents. The collected data were edited, coded and entered into Epi-Data version 3.1 and export to SPSS version 20 software for further data management and analysis. Summary measures like percentage mean and the standard deviation werecomputed and presented in tables.A simple logistic regression model was tted to identify factors associated with non-Hodgkin's lymphoma. Crude and adjusted odds ratios (OR) with a 95% CI were computed to assess the strength of association between the independent and outcome variables.
Variables with a p-value of less than 0.05 were considered as statistically signi cant predictors of non-Hodgkin's lymphoma.

Ethical Consideration
Ethical approval was obtained from the research Ethical Review Board of Bahir Dar University with reference number. After receiving a permission letter from the regional health bureau. Before the beginning of data collection, permission letter was obtained from Amhara National Regional Institute of Public Health and from each concerned body prior to the data collection period. Written consent was received from the study participants only. However, for fewer than 16 years old, written consent was taken from parents/guardians and assent from study members were secured. Names of the respondents did not use to ensure anonymity and con dentiality. All information obtained from the respondents was kept con dential.

Results
Descriptive Statistics forsocio-demographic characteristics A total of 486 (162 cases 324 and controls) study participants at follow up in Felegehiwot specialized Hospital were interviewed and yielded a response rate of 100%.
A larger portion of cases (34%) and controls (35.2 %) were in the age group of 46-60 years. About ninety percent of cases and controls were Orthodox Christian. Majority of the cases (84 %) and controls (84.3 %) were from the Amhara ethnic group. About two-thirds of cases and controls were unable to read and write. The majority of the cases and controls were married. More than three-fourths of the respondents come froma rural area,and more than one-fourthof the respondents were farmers ( Table 2). Chemical exposure-related characteristics About seventy-eight percent of the cases and twenty-two percent of the controls had previous exposure to carcinogenic chemicals. From these, more than one-third of the respondents were exposed toHerbicides.
Half of the respondents exposed for more than fteen years. About eight percent of the cases and ve percent of the controls were cigarette smokers; of which, fty-four percent of cases and sixty-two percent of controls smoked for more than ten years, respectively. Eighty-six percent of cases and sixty-seven percent of controls had drunken alcohol. Eighty-eight percentof cases and eighty-three percent of controls had drunken cultural alcohol. Eighty-six percent of cases and seventy-four percent of controls were coffee drunker. Of which, three-fourth of the respondents drunk coffee for more than thirty years. (Table 3) Behavioral and nutrition-related characteristics More than two-thirds of the respondents had regular physical exercise, and more than halfof the cases had a history of chronic illness. More than one-third of the cases (40%) and one-fourth of controls (26%) had lung disease (COPD). Two-third of the cases and about sixty percent of controls didn't know their HIV status. More than one-fourth of the cases and controls have started treatment on time. (Table 4) Variables having a p-value less than 0.2 were takeninto multiple logistic regressions as signi cant. Hence, it was found out that some socio-demographic determinants like residence, monthly income, sex (male), chemical exposure-related determinants like Ever had Chemical exposureand drinking alcohol; Behavioral and nutrition-related determinants; Physical exercise/sport and type of chronic diseasewere eligible to enter to multiple regressions before. However; residence,occupation anddrink alcohol were not statistically associated with the outcome variable (Table 5).

Socio-demographic determinants of NHL
After adjusting the potential confounders (chemical exposure and behavioral and nutrition) monthly income and sex were found to bedeterminants for non-Hodgkin's lymphoma.
Respondents whose monthly income of less than or equal to 28 dollarswereabout three times more likely at risk for non-  (Table 5). This study investigated different exploratory variables and identi ed the root causes of non-Hodgkin's lymphoma. It was recognized that monthly income wasone of the crucial determinants for the root causes of non-Hodgkin's lymphoma. Respondents who had monthly income of less than or equal to 28 dollarswere about three-foldmore at risk to NHL compared towho had greater than 28 dollars. This nding is supported by a study done at GlostrupUniversity Hospital, Denmark [11]This might be as having littleincome and deprived living status could be the risk factorfor non-Hodgkin's lymphoma. As a result, may down the chance of study participants to gain awareness in non-Hodgkin's lymphoma. It is also could be justi ed, even if the study participants had health-seeking behavior, they become tied to not gaining it due to the inability to cover the cost of the service. That might also increase the risk of non-Hodgkin's lymphoma.

Sex
The odds of having NHL in males were 2 times compare tofemales.This is supported by a study done in Yale University, USA [1].The reason for this risk difference between the two sexes could be males in our country are highly exposed to out-door work. And the majority of the respondents in our study were farmers, which their work is mainly con ned to farm work. As a result, they may be more exposed to carcinogenic chemicals like herbicides and pesticides.
Ever had chemical exposure It was found out in this study that, respondents who had chemical exposure were 12 times more likely at risk for NHL than their counterparts. This is supported by a study done in the Yale University, USA [1],a meta-analysis [12], and Sweden [8]. However, a study nding in the USA showed that respondents who exposed to chemicals were protected from [13].
This is becausethe majority of chemicals are carcinogenic by their nature and the current study showed four times risk factors compare to the developed country was conducted. This may be the result of our country population might havepoor knowledge and understanding about the dangerous chemicals and how to use than Indian and Sweden population.

Regular physical exercise
The odds of being caught by NHL from non-regular physical exercising respondents were about ve times more likely at risk than those who did in the past. This nding is supported by a case-control study conducted in California [14]and a study in Canada, Ottawa [15].There is big risk difference between the current study and the latter two studies. This might be as a result ofa regular physical exercise in our country is not as habitual as compared to California and Canada population.

Type of chronic disease
The current study revealed that the likelihood of risk for NHL among various chronic ill patients was different. Respondents who had a chronic disease like hypertension-related, lung disease and others (CKD, PUD and Cardiac failure) 97%, 78.8% and 95% less at risk for NHL compared to those who had diabetes mellitus respectively. This study nding supported by a meta-analysis study [16] as DM patients were at high risk for NHL. However, the underlying mechanism is unclear. The possible justi cation might be Diabetes Mellitus; especially type two is an autoimmune disease which as a result may aggravate the likelihood for the NHL occurrence.Future studies should focus on elucidating potential pathophysiologic links between diabetes and NHL.

Strength of the study
Since the study design was a case-control study, it gave more strong evidence on the determinants of NHL compared to cross-sectional and other descriptive studies.
Limitation of the study