1. Cancer and the General Internist
Lance Catedral, MD, MCM(MO), FPCP
General Santos City
10 February 2021
✉ lance@bottledbrain.com 🐦 @lanceoncology

2. Disclosures
• None to declare

3. How can general internists
participate in the continuum of care
for patients with cancer?

4. Outline
• Burden of cancer
• Cancer screening
• Cancer prevention strategies
• Environmental factors
• Physical activity
• Obesity
• Diet
• Infection
• Chemoprevention

5. • Cancer — third leading cause of death in the Philippines
• Projected to exceed cardiovascular and metabolic diseases as leading
cause of mortality and morbidity

6. BROAD SOCIAL CONTEXT
Health system
N
ational cancer control pl
a
n
Early
diagnosis
Screening Treatment
Prevention
Palliative
care
Survivorship
care
Figure 1. Comprehensive cancer control
Source: Adapted from WHO 2002 (7).
Guide to cancer early diagnosis. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.

7. Cancer treatment is costly
Because medical oncologists need to discuss the costs of
biomarker tests and subsequent therapeutic options with
their patients before treatment, the use of biomarkers as the
lynchpin of treatment planning may prove difficult in
the setting of LMICs. This is an important consideration in
the effort to harmonize treatment guidelines on molecular
members and 57 fellows-in-training). The aim of this study
was to describe the patterns of biomarker testing among
medical oncologists in the Philippines for the management of
breast, colorectal, and lung cancers, the country’s top three
malignancies.22
In addition, we aimed to identify the driving
factors and barriers to biomarker use in the country.
TABLE 1. Guideline Recommendations for Biomarker Use in Specific Cancers by NCCN, ASCO, and ESMO, and Cost of Test in the Philippines
Biomarker Key Indications
Cost of Biomarker Test
(USD)
Breast cancer7-12
ER All stages 80-100
PR All stages 80-100
HER2 All stages 70-80
Oncotype DX, MammaPrinta
Early, hormone receptor positive, HER2 negative 4,000
Colorectal cancer13-16
RAS (KRAS/NRAS) Metastatic 560-820
BRAF Metastatic 400-600
MSI and/or MMR All stages, for those with personal history of colorectal
cancer
280-300
Lung cancer17-19
EGFR (exon 19, exon21 L858R, other less common
mutations)
Advanced/metastatic NSCLC 360-480
ALK Advanced/metastatic NSCLC 40-120
ROS1 Advanced/metastatic NSCLC 370
BRAF Advanced/metastatic NSCLC 550
PD-L1 Advanced/metastatic NSCLC 360
Abbreviations. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; ER/PR, estrogen receptor/progesterone receptor; ESMO,
European Society for Medical Oncology; HER2, human epidermal growth factor receptor 2; MMR, mismatch repair; MSI, microsatellite instability; NCCN,
National Comprehensive Cancer Network; NSCLC, non–small-cell lung cancer; USD, US dollars.
Catedral LI, Tan HN, Chua A, Sacdalan DB, and Sacdalan D. JCO Global Oncol 6:1593-1608.

8. Guideline recommendation was the most
vation for biomarker testing. This mirrored
a similar survey of oncologists from other cou
absence of local guidelines, medical onc
Philippines refer to guidelines developed by
and ESMO. Updated regularly, these reflec
of care in developed regions with ready acc
edge molecular tests and targeted treatmen
be available in the Philippines. Recently, r
lines have emerged to adapt western guideli
account ethnic differences associated with t
metastatic NSCLC cancer in Asian patients.
part of the consensus panel for these gu
these Pan-Asian guidelines might not be dire
in the Philippine setting.26
For the three cancers, evidence shows that b
guide treatment planning for the first and sub
Related to this, our results showed that med
used biomarker testing to explore alterna
options.
Of note, almost half reported using biomarke
their patients were included in clinical tr
Testing was likely required before enrollme
who practiced in academic medical cente
more exposure to clinical trials. We showe
TABLE 4. Driving Factors for and Barriers to Biomarker Use
Variable No. (%)
Driving factors
Tests are based on clinical practice guidelines 122 (96.06)
Patient has advanced or metastatic disease 97 (76.38)
Patient is included in clinical trial 63 (49.61)
No other treatment options exist; biomarkers may
lead to more options
54 (42.52)
Test is based on the institution’s oncology pathway/
protocol
46 (36.22)
Barriers
Patients experience financial constraints 120 (94.49)
Patients do not want to be tested 75 (59.06)
Test is not available in area of practice 74 (58.27)
There is insufficient tissue sample 60 (47.24)
Test results come out late 9 (7.09)
Tests do not change clinical decision and
management
7 (5.51)
Medical oncologist is not familiar with test 4 (3.15)
Medical oncologist is familiar with test but believes
that there are not enough study data to support
testing
3 (2.36)
1598 © 2020 by American Society of Clinical Oncology
Catedral LI, Tan HN, Chua A, Sacdalan DB, and Sacdalan D. JCO Global Oncol 6:1593-1608.

9. Cancer leads to financial catastrophe
in 40.6% of Filipino patients
plans
using
cancer while it occurred the least in those with respiratory
cancer. Meanwhile, the highest death rate occurred among
the respiratory group and the least among those with breast
cancer (Figure 4).
r type,
23.8
33.3
11.0
5.9
9.4
16.6
4.2
23.1
29.3
20.7
22.8
ough
9.05
6.14
Figure 4. Households with financial catastrophe (FC) by cancer
site, Month 12 (n=909).
Mean combined
month 3 and month
12 out-of-pocket
expenditure:
Php 181,789.00
(SD 358,717.47) (1)
(1) Ngelangel C, Lam HY, Rivera AS, Kimman ML, Real IO, Balete S, Philippines ACTION Study Group. Philippine Costs in Oncology (PESO): Describing the Economic Impact
of Cancer on Filipino Cancer Patients Using the ASEAN Costs in Oncology Study Dataset. Acta Med Philipp 52:125-133, 2018 (2) Philippine Statistics Authority: Statistical Tables
on 2018 Family Income and Expenditure Survey, 2020. https://psa.gov.ph/content/statistical-tables-2018- family-income-and-expenditure-survey
Average household
income in Philippines:
Php 26,000 (2)

10. Cancer care is multidisciplinary

11. Filipinos actively look for cancer-related
information
• A total of 806 cancer-related search terms were identified, with 13,632,890 Google
web searches, during the period under review.
• The top ten search terms with the highest monthly search volume in the
Philippines (n=4,741,600, 34.78%) were “cancer,” “breast cancer,” “cervical
cancer,” “prostate cancer,” “colon cancer,” “breast cancer symptoms,” “lung
cancer,” “lung cancer symptoms,” “colon cancer symptoms,” and “lungs.”
• In this time period, Filipinos sought information on cancer-related signs and
symptoms (n=3,307,640, 24.26%) and cancer treatment (n=604,070, 4.43%).
• Filipinos also searched for alternative, herbal, and natural cancer treatments, but
the search volume accounted for a low percentage of the total searches (n=8,710,
0.06%).
Catedral LI, Leones LMB, Berba CM. What Filipinos, the world’s number one Internet users, want to know about cancer: A Google search analysis from 2015 to 2019. Journal of Global
Oncology 2019 5:suppl, 23-23

12. were screened using different tests. Three (1.15%) were advised FOBT, one was
advised sigmoidoscopy, and another one was advised colonoscopy. All but two
patients advised FOBT were appropriately screened.
Table 1. Number of Patients Eligible for Cancer Screening, Proportion of
Eligible Patients Screened, and Appropriateness of Tests Ordered
Eligible Screened (%) Tests Requested
Appropriately (n)
Breast 149 6 (4.03%) Mammogram (6)
Cervical 204 8 (3.92%) Pap smear (2)
Colorectal 260 5 (1.92%) FOBT (1)
Sigmoidoscopy (1)
Colonoscopy (1)
2. Resident Survey
There were 56 respondents, comprised of 28 males and 28 females, with a
mean age of 27.7. There were 19 first year residents, 18 second year residents, and
Quero A, Ceralde A, Silla G, Palileo-Villanueva. 2016. Unpublished. Cancer Screening Knowledge, Attitudes, and Adherence of Residents at the General Medicine Out-patient Clinic of the
Philippine General Hospital

13. screening.
Figure 2. Perceived factors to implementation of cancer screening (N= 56)
For the patient-related factors, 62.50% of the surveyed residents agreed that
-100 -50 0 50 100
Lack of knowledge of guidelines
Trust in the guideline developer
Fear of being diagnosed with
Doubt in effectiveness of screening
Anxiety or embarrassment
Not aware of screening test
Values as non-influential
Cost of screening test
Unavailability of screening test
Shortage of personnel to conduct
Strongly Disagree Disagree Agree Strongly Agree
Physician-related
Factors
Patient-related
factors
Systems-related
factors
Quero A, Ceralde A, Silla G, Palileo-Villanueva. 2016. Unpublished. Cancer Screening Knowledge, Attitudes, and Adherence of Residents at the General Medicine Out-patient Clinic of the
Philippine General Hospital

14. tion is evaluated for unrecognized cancer or precancer and the majority of individuals
tested will not have the tested disease (Figure 2).
Screening should be viewed as a process not as administering a particular test, exam-
Figure 2. Distinguishing screening from early diagnosis according to symptom onset
Healthy
cells
Symptom
onset
Service provided for a target population Service provided only for people with symptoms
Early diagnosis
Abnormal
cells
Pre-invasive
cancer
Invasive
cancer
Cancer
spread
Death
Screening
Guide to cancer early diagnosis. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.

15. Why screen?
• Ultimate goal — decrease mortality

16. Cancer screening
• Breast cancer
• Colorectal cancer
• Cervical cancer
• Hepatocellular cancer
• Prostate cancer

17. Breast cancer screening: average risk
• Risk of being diagnosed with, not of dying from
• First, determine the risk
• High risk:
• Personal history of breast, ovarian, tubal, or peritoneal cancer
• Family history of breast, ovarian, tubal, or peritoneal cancer
• Ancestry (eg, Ashkenazi Jewish) associated with BRCA1 or 2 mutations
• Known carrier of a pathogenic mutation for a hereditary breast and ovarian cancer syndrome in self or relative
• Mammographic breast density
• Previous breast biopsy indicating high-risk lesion (eg, atypical hyperplasia)
• Age of menarche, age at first live birth, number of pregnancies, and menopausal status
• Radiotherapy to the chest between age 10 and age 30

18. Screenshot: https://bcrisktool.cancer.gov

19. Elmore and Lee , 2021, Screening for breast cancer: Strategies and recommendations, https://www.uptodate.com/contents/screening-for-breast-cancer-strategies-and-recommendations?
search=cancer%20screening&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=2#H3838866944

20. Graphic 113796 Version 4.0
© 2021 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

21. Figure 1. Effects of screening on breast cancer mortality.
Author, Year (Reference) Trial Name
Women aged 39–49 y
Nyström et al, 2002 (30)*
Tabár et al, 1995 (26)
Tabár et al, 1995 (26)
Moss et al, 2015 (27)
Bjurstam et aI, 2003 (25)
Habbema et aI, 1986 (29)
Nyström et al, 2002 (30)*
Nyström et al, 2002 (30)*
Miller et aI, 2014 (15)
Overall (I2
= 25%; P = 0.230)
Women aged 50–59 y
Tabár et al, 1995 (26)
Tabár et al, 1995 (26)
Nyström et al, 2002 (30)*
Bjurstam et aI, 2003 (25)
Habbema et aI, 1986 (29)
Nyström et al, 2002 (30)*
Miller et aI, 2014 (15)
Overall (I2
= 38.0%; P = 0.139)
Women aged 60–69 y
MMST ll
Kopparberg
Östergötland
Age
Gothenburg
HIP
Stockholm
MMST l
CNBSS-1
Östergötland
Kopparberg
Stockholm
Gothenburg
HIP
MMST l
CNBSS-2
11.2
12.5
12.5
17.5
13.8
14.0
14.3
18.2
21.9
12.5
12.5
13.7
13.8
14.0
18.1
21.9
0.64 (0.39–1.06)
0.73 (0.37–1.41)
1.02 (0.52–1.99)
0.93 (0.80–1.09)
0.69 (0.45–1.05)
0.75 (0.53–1.05)
1.52 (0.80–2.88)
0.74 (0.42–1.29)
1.04 (0.87–1.24)
0.92 (0.75–1.02)
0.85 (0.52–1.38)
0.48 (0.29–0.77)
0.56 (0.32–0.97)
0.83 (0.60–1.15)
0.83 (0.61–1.13)
0.98 (0.75–1.29)
0.94 (0.78–1.13)
0.86 (0.68–0.97)
Mean
Follow-up, y
Relative Risk (95% CI)
Effects of screening on mortality

22. Favors
Screening
Group
0.25 1.00 4.00
Favors
Control
Group
Women aged 50–59 y
Tabár et al, 1995 (26)
Tabár et al, 1995 (26)
Nyström et al, 2002 (30)*
Bjurstam et aI, 2003 (25)
Habbema et aI, 1986 (29)
Nyström et al, 2002 (30)*
Miller et aI, 2014 (15)
Overall (I2
= 38.0%; P = 0.139)
Women aged 60–69 y
Tabár et al, 1995 (26)
Tabár et al, 1995 (26)
Nyström et al, 2002 (30)*
Habbema et aI, 1986 (29)
Nyström et al, 2002 (30)*
Overall (I2
= 0.0%; P = 0.739)
Women aged 70–74 y
Tabár et al, 1995 (26)
Tabár et al, 1995 (26)
Nyström et al, 2002 (30)*
Overall (I2
= 0.0%; P = 0.962)
Östergötland
Kopparberg
Stockholm
Gothenburg
HIP
MMST l
CNBSS-2
Kopparberg
Östergötland
Stockholm
HIP
MMST l
Östergötland
Kopparberg
MMST I
12.5
12.5
13.7
13.8
14.0
18.1
21.9
12.5
12.5
13.1
14.0
15.5
12.5
12.5
13.6
0.85 (0.52–1.38)
0.48 (0.29–0.77)
0.56 (0.32–0.97)
0.83 (0.60–1.15)
0.83 (0.61–1.13)
0.98 (0.75–1.29)
0.94 (0.78–1.13)
0.86 (0.68–0.97)
0.58 (0.35–0.96)
0.62 (0.43–0.91)
0.94 (0.46–2.02)
0.85 (0.48–1.47)
0.64 (0.45–0.92)
0.67 (0.54–0.83)
0.82 (0.43–1.58)
0.76 (0.42–1.36)
0.98 (0.15–6.60)
0.80 (0.51–1.28)
Nelson, H. D., Fu, R., Cantor, A., Pappas, M., Daeges, M., & Humphrey, L. (2016). Effectiveness of Breast Cancer Screening:
Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation. Annals of Internal
Medicine, 164(4), 244. doi:10.7326/M15-0969

23. groups, indicated a risk reduction of 0.75 (CI, 0.69 to cancer mortality after changing from annual to biennial
Table 1. Age-Specific Rates of Breast Cancer Mortality Reduction With Screening
Age Mortality Rate in the
Control Group per 100 000
Person-Years (95% CI)*
Breast Cancer
Mortality Reduction:
Relative Risk (95% CI)†
Deaths Prevented With
Screening 10 000 Women
Over 10 Years (95% CI)
Long case accrual
39–49 y 36 (29 to 43) 0.92 (0.75 to 1.02) 2.9 (–0.6 to 8.9)
50–59 y 54 (50 to 58) 0.86 (0.68 to 0.97) 7.7 (1.6 to 17.2)
60–69 y 65 (52 to 81) 0.67 (0.54 to 0.83) 21.3 (10.7 to 31.7)
70–74 y 62 (48 to 80) 0.80 (0.51 to 1.28) 12.5 (–17.2 to 32.1)
50–69 y 58 (55 to 62) 0.78 (0.68 to 0.90) 12.5 (5.9 to 19.5)
Short case accrual
39–49 y 22 (16 to 30) 0.87 (0.72 to 1.00) 2.9 (0.1 to 6.5)
50–59 y 31 (24 to 39) 0.86 (0.69 to 1.01) 4.5 (–0.2 to 9.8)
60–69 y 40 (28 to 56) 0.67 (0.55 to 0.91) 12.1 (3.4 to 20.7)
70–74 y 49 (36 to 64) 0.90 (0.46 to 1.78) 12.2 (–37.7 to 26.9)
50–69 y 32 (24 to 41) 0.81 (0.69 to 0.95) 6.1 (1.2 to 10.9)
* On the basis of trials of screening included in the meta-analysis.
† From meta-analyses of screening trials using 2 different methods of case accrual. The long case accrual method counts all breast cancer cases
contributing to breast cancer deaths. In this method, the case accrual time is equivalent to or close to the follow-up time. The short case accrual
method includes only deaths that occur among cases of breast cancer diagnosed during the screening intervention period, and in some trials,
within an additional defined case accrual period.
REVIEW Effectiveness of Breast Cancer Screening
Nelson, H. D., et al. Annals of Internal Medicine, 164(4), 244. doi:10.7326/M15-0969
Age-specific rates of breast cancer mortality
reduction with screening

24. • Average risk → <15% lifetime risk of developing breast cancer
• Summary of recommendations for women:
• <40 years old: mammography not recommended
• 40 to 49 years old: shared decision making
• 50 to 74 years old: screening is recommended
• >75 years: only screen if life expectancy is at least 10 years

25. What about…?
• Ultrasound — not recommended
• MRI — not recommended for average risk
• Self-breast examination (SBE)
• Lack of benefit, higher rate of breast biopsy that shows benign disease
• But it can empower and raise awareness among women (WHO)

26. How to screen
• Mammography every 1 to 2 years

27. Colorectal cancer: average risk
• Assess the risk
• Have you ever had CRC or an adenomatous polyp?
• Have any family members had CRC or a documented advanced polyp?
• If so, how many family members, were they first-degree relatives (parent, sibling, or
child), and at what age was the cancer or polyp first diagnosed?
• Do you have family members with any of the known genetic syndromes that can cause
CRC?
• Do you have inflammatory bowel disease (ulcerative colitis or Crohn disease)
• Did you receive abdominal radiation for childhood cancer?
Doubeni C. Screening for colorectal cancer: Strategies in patients at average risk. https://www.uptodate.com/contents/screening-for-colorectal-cancer-strategies-in-patients-at-average-risk?
search=cancer%20screening&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#references

28. • Start screening at age 50
• Preferred tests:
• colonoscopy once every 10 years
• fecal immunohistochemical staining (FIT for occult blood) annually
• if (+) for occult blood → prompt colonoscopy
• FIT has better sensitivity without loss of specificity and better detects
adenomas (1-4)
• computed tomography colonograpy (virtual colonoscopy) once every 5 years
1. JAMA. 2016 Jun;315(23):2576-94; 2. Gastrointest Endosc. 2017;85(1):2. Epub 2016 Oct 18.; 3. Ann Intern Med. 2017;166(4):297; 4. Br J Cancer. 2009;100(8):1230. Epub 2009 Mar 31.

29. • Other screening tests
• Sigmoidoscopy combined with FIT (or sensitive gFOBT)
• Sigmoidoscopy every 10 years, with annual FIT (1,2)
• Sigmoidoscopy every 5 years with annual FOBT (3)
• Sigmoidoscopy every 5 years with FOBT/FIT every three years (4)
• Sigmoidoscopy alone, once every 5 to 10 years
• Stool guaiac tests (gFOBT) annually
• Capsule colonoscopy every 5 years
1. UPSTF, JAMA. 2016 Jun;315(23):2564-75; 2. ASCO, J Glob Oncol. 2019;5:1; 3. NCCN, J Natl Compr Canc Netw. 2013;11(12):1538. 4. Ann Intern Med. 2015;162(10):718.

30. In resource-limited settings
• In a basic setting, highly sensitive gFOBT every one (preferred) to two
years
• FIT as an alternative
• In a limited setting with more resources (1)
• highly sensitive gFOBT yearly
• sigmoidoscopy every five years with suggested alternatives of FIT yearly
• sigmoidoscopy every 10 years plus yearly FIT (preferred) or yearly FOBT
(1) Lopes G. J Glob Oncol. 2019;5:1

31. • if stool-based test is positive → colonoscopy within three months

32. Cervical cancer: average risk
Feldman et al. 2021. Screening for cervical cancer in resource-rich settings.

33. Society of Gynecologic Oncology:
Clinical Practice Guidelines for
Obstetrician-Gynecologists. Third Ed.,
July 2019

34. Society of Gynecologic Oncology:
Clinical Practice Guidelines for
Obstetrician-Gynecologists. Third Ed.,
July 2019

35. Hepatocellular cancer
• Patients at risk for HCC
• Cirrhosis
• Hepatitis B and C
• Alcohol
• Genetic hemochromatosis
• Non-alcoholic fatty liver disease
• Stage 4 primary biliary cholangitis
• Alpha-1-antitrypsin deficiency
• Without cirrhosis
• Hepatitis B
• Ultrasound +/- AFP (alpha
fetoprotein) every 6 months
NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 5.2020 — August 4, 2020

36. Lung Cancer
• Low-dose chest CT scan
• non-contrast study obtained with a multi detector CT scanner during a maximal
inspiratory breath-hold with a scanning time under 25 seconds
• Annual LDCT:
• men and women
• 55 to 74 years old
• history of at least 30-pack year smoking
• discontinued smoking within 15 years

37. Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer
The National Lung Screening Trial Research Team. N Engl J Med 2011;365:395-409
relative reduction in mortality from lung cancer
with low-dose CT screening of 20.0% (95%
CI, 6.8 to 26.7; P=0.004)
the rate of death from any cause was reduced
in the low-dose CT group, as compared with
the radiography group, by 6.7% (95% CI, 1.2
to 13.6; P=0.02)

38. Summary of cancer screening for average risk
patients
Malignancy General recommendations
Breast cancer Starting 50 years old, mammogram annually
Colorectal cancer
Starting 50 years old:
colonoscopy every 10 years
FIT every 1-2 years (alternatively, use FOBT)
Cervical cancer
Starting 21 years old, pap smear every three years
Starting 30 years old:
pap smear every three years
pap smear + HPV co-testing every five years
Hepatocellular cancer
With cirrhosis or hepatitis B and C:
Liver ultrasound +/- AFP every 6 months
Lung cancer
55-74 years old, 30-pack years, quit within 15 years:
annual low dose CT scan

39. Cancer Prevention Strategies

40. 1. Avoid tobacco
2. Be physically active
3. Maintain a healthy weight
4. Eat a diet rich in fruits, vegetables, and whole grains and low in
saturated/trans fat, red meat, and processed meat
5. Limit alcohol (zero is best)
6. Protect against sexually transmitted infections; vaccinate girls and boys
against human papillomavirus (HPV)
Colditz GA. Jan 2021. https://www.uptodate.com/contents/cancer-prevention?source=autocomplete&index=0~1&search=cancer%20prevention

41. 1. Avoid tobacco
• most preventable cause of cancer (1)
• 1/2 of all smokers die of a tobacco-
related disease (2–4)
• adult smokers lose an average of 13
years of life due to tobacco use (2–4)
(1) Brawley OW. CA Cancer J Clin. 2011;61(2):67. (2) BMJ. 1994;309(6959):901. (3) MMWR Morb Mortal Wkly Rep. 2002;51(14):300. (4) MMWR Morb Mortal Wkly Rep. 2016;65(44):1212. Epub
2016 Nov 11.

42. the evaluation of the evidence
tudies in humans*
efinition
siders that a causal relationship
etween exposure to the agent,
rcumstance and human cancer.
tionship has been observed
and cancer in studies in which
ounding could be ruled out
ence
s been observed between
mixture or exposure
er for which a causal
ered by the Working Group to
e, bias or confounding could
easonable confidence.
of insufficient quality,
cal power to permit a
he presence or absence of a
ween exposure and cancer, or
umans are available.
te studies covering the full
osure that human beings are
which are mutually consistent in
Table 2. Cancer sites for which there is “sufficient” evidence of
carcinogenicity of tobacco smoking according to the International Agency for
Research on Cancer Working Group*
Cancer site
No. of studies
evaluated
Avg relative
risk
Case–control Cohort
Lung "100 37 15.0–30.0
Urinary tract 50 24 3.0
Upper aero-digestive tract:
Oral cavity 16 3 4.0–5.0
Oro-and hypopharynx 12 3† 4.0–5.0‡
Oesophagus (SCC or NOS) 35 19§ 2.0–5.0
Larynx 25 5 10.0‡
Esophagus (adenocarcinoma) 10 NA 1.5–2.5
Pancreas 38 27 2.0–4.0
Nasal cavity, paranasal sinuses 9 1 1.5–2.5
Nasopharynx 19 2 1.5–2.5
Stomach 44 27 1.5–2.0
Liver 29 29 1.5–2.5
Kidney 13 8 1.5–2.0
Uterine cervix 49 14! 1.5–2.5
Myeloid leukemia Not reviewed 12 1.5–2.0
*SCC ! squamous cell carcinoma; NOS ! not otherwise specified; CIS !
carcinoma in situ; CIN ! cervical intraepithelial neoplasia; NA ! not available.
Downlo
Vineis, P., et al (2004). Tobacco and Cancer: Recent Epidemiological Evidence. JNCI Journal of the National Cancer Institute, 96(2), 99–106.

44. Image source: https://www.instagram.com/p/CDncddeBLa3/
Instagram: @cancerexperts

45. Lung cancer mortality and smoking cessation
continued smoking is associated with an exponential increase of
the cumulative lung cancer mortality with age (56). Compared
with smokers who continue to smoke, the increase in lung cancer
mortality is lower for individuals who quit smoking by age 50
years and even lower for individuals who quit smoking by age
Alcohol, tobacco and breast cancer—collaborative re
data from 53 epidemiological studies, including 58 51
cancer and 95 067 women without the disease. Br J C
45.
(6) Adami HO, Bergstrom R, Engholm G, Nyren O, Wo
A prospective study of smoking and risk of prostate
1996;67:764–8.
(7) Giovannucci E, Rimm EB, Ascherio A, Colditz
Stampfer MJ, et al. Smoking and risk of total and fa
United States health professionals.Cancer Epidem
1999;8:277–82.
(8) Terry PD, Rohan TE, Franceschi S, Weiderpass E.C
the risk of endometrial cancer. Lancet Oncol 2002;3
(9) Vaughan TL, Shapiro JA, Burt RD, Swanson GM, B
et al. Nasopharyngeal cancer in a low-risk population
by histological type.Cancer Epidemiol Biomarkers P
(10) Yuan JM, Wang XL, Xiang YB, Gao YT, Ross RK,
risk factors for nasopharyngeal carcinoma in Shangha
2000;85:364–9.
(11) Zhu K, Levine RS, Brann EA, Gnepp DR, Baum M
and nasopharyngeal cancer: an analysis of the relation
at starting smoking and age at diagnosis. J Epidemio
(12) Chao A, Thun MJ, Henley SJ, Jacobs EJ, McCull
Cigarette smoking, use of other tobacco products
mortality in US adults: the Cancer Prevention Stu
2002;101:380–9.
(13) McLaughlin JK, Hrubec Z, Blot WJ, Fraumeni JF Jr
cigarette smoking among U.S. veterans, 1954–1980.
3804.
(14) Akiba S, Hirayama T. Cigarette smoking and can
Japanese men and women—results from reanalysis
cohort study data. Environ Health Perspect 1990;87:
(15) Tredaniel J, Boffetta P, Buiatti E, Saracci R, Hirsch
and gastric cancer: review and meta-analysis. Int J Ca
(16) Liu BQ, Peto R, Chen ZM, Boreham J, Wu YP, L
tobacco hazards in China: 1. Retrospective proportio
one million deaths. BMJ 1998;317:1411–22.
Vineis, P., Alavanja, M., Buffler, P., Fontham, E.,
Franceschi, S., Gao, Y. T., … Doll, R. (2004). Tobacco
and Cancer: Recent Epidemiological Evidence. JNCI
Journal of the National Cancer Institute, 96(2), 99–
106.

46. Evidence-based guidelines for smoking cessation
• Key points:
• Tobacco dependence — a chronic condition that warrants repeated treatment
• Effective treatments for tobacco dependence exist and all tobacco users should be
offered those treatments.
• Clinicians and health care delivery systems must institutionalize the consistent
identification, documentation, and treatment of every tobacco user at every visit.
• Brief tobacco dependence treatment is effective, and every tobacco user should be
offered at least brief treatment.
• There is a strong dose-response relationship between the intensity of tobacco
dependence counseling and its effectiveness.
The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. (2000). A Clinical Practice Guideline for Treating Tobacco Use and Dependence: A US
Public Health Service Report. JAMA: The Journal of the American Medical Association, 283(24), 3244–3254.

47. Evidence-based guidelines for smoking cessation
• Three types of counseling were found to be especially effective-practical counseling, social support
as part of treatment, and social support arranged outside of treatment.
• Five first-line pharmacotherapies for tobacco dependence are effective
• sustained-release bupropion hydrochloride
• nicotine gum
• nicotine inhaler
• nicotine nasal spray
• nicotine patch-are effective
• Tobacco dependence treatments are cost-effective relative to other medical and disease prevention
interventions
The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. (2000). A Clinical Practice Guideline for Treating Tobacco Use and Dependence: A US
Public Health Service Report. JAMA: The Journal of the American Medical Association, 283(24), 3244–3254.

48. 2. Be physically active
J Clin Oncol. 2020 Mar 1;38(7):686-697. doi: 10.1200/JCO.19.02407.

49. • Physical activity is associated with a decreased risk for many different
types of cancers
• Most compelling data: colon and breast cancer
• negative correlation between moderate-strenuous exercise and
estrogen receptor-negative breast cancer (1)
• 24 % reduced risk of colon cancer for active individuals vs inactive
individuals (relative risk [RR] 0.76, 95% CI 0.72-0.81) (2)
(1) Arch Intern Med. 2007;167(4):408. (2) Br J Cancer. 2009;100(4):611. Epub 2009 Feb 10.

50. • the protective effect of activity goes beyond its impact on body weight
• suggested mechanisms (1–3):
• reduction in circulating levels of insulin, hormones, and other growth
factors
• impact on prostaglandin levels
• improved immune function
• altered bile acid metabolism
(1) Cancer Epidemiol Biomarkers Prev. 1994;3(8):687. (2) Ann Intern Med. 1995;122(5):327. (3) J Natl Cancer Inst. 1999;91(11):950.

51. 3. Maintain a healthy weight
• Obesity estimated to cause 20 percent of cancers (1)
• International Agency for Research on Cancer’s conclusion:
• the absence of excess body fat had a cancer preventive effect in many
malignancies (2)
• Weight loss methods associated with decreased cancer mortality
• bariatric surgery — 60 percent reduction in cancer mortality (5.5 versus
13.3 per 10,000 person-years) (3)
(1) Oncologist. 2010;15(6):556. Epub 2010 May 27. (2) N Engl J Med. 2016;375(8):794. (3) N Engl J Med. 2007;357(8):753.

52. 1. Eat a diet rich in fruits, vegetables, and whole grains and
low in saturated/trans fat, red meat, and processed meat
Table 1 Results from large prospective studies on fruit and vegetables and risk of colorectal cancer, lung cancer, breast cancer and all cancers
Cancer site and study Reference
Number of
cancers
RR (95% CI)
for high fruit
consumption
RR (95% CI)
for high vegetable
consumption
RR (95% CI)
for high fruit and vegetable
consumption
Colorectal cancer
EPIC van Duijnhoven et al (2009) 2819 0.88 (0.76–1.01) 0.92 (0.79–1.06) 0.86 (0.75–1.00)
NIH-AARP Park et al (2007) 2048 Men 1.06 (0.91–1.23) 0.82 (0.71–0.94) 0.91 (0.78–1.05)
924 Women 1.09 (0.88–1.36) 1.12 (0.90–1.38) 1.08 (0.86–1.35)
Pooling Project (colon only) Koushik et al (2007) 5838 0.93 (0.85–1.02) 0.94 (0.86–1.02) 0.91 (0.82–1.01)
Lung cancer
EPIC Büchner et al (2010) 1830 0.80 (0.66–0.96) 0.96 (0.79–1.17) —
NIH-AARP Wright et al (2008) 3834 Men 0.91 (0.82–1.02) 0.93 (0.83–1.03) 0.93 (0.83–1.04)
2201 Women 0.97 (0.84–1.11) 1.05 (0.92–1.21) 0.98 (0.85–1.13)
Pooling Project Smith-Warner et al (2003) 3206 0.77 (0.67–0.87) 0.88 (0.78–1.00) 0.79 (0.69–0.90)
Breast cancer
EPIC van Gils et al (2005) 3659 1.09 (0.94–1.25) 0.98 (0.84–1.14) —
Pooling Project Smith-Warner et al (2001) 7377 0.93 (0.86–1.00) 0.96 (0.89–1.04) 0.93 (0.86–1.00)
All cancers
EPIC Boffetta et al (2010) 30 604 0.94 (0.90–0.98) 0.93 (0.89–0.97) 0.89 (0.85–0.93)
Japan Public Health Center-Based
Prospective Study
Takachi et al (2008) 3230 1.02 (0.90–1.14) 0.94 (0.84–1.05) 0.96 (0.85–1.07)
NIH-AARP Diet and Health Study George et al (2009) 35 071 Men 0.98 (0.95–1.02) 0.94 (0.91–0.97) —
15 792 Women 0.99 (0.94–1.05) 1.04 (0.98–1.09) —
Fruit and vegetables and cancer risk
TJ Key
8

53. (Kavanaugh et al, 2007). Studies of soyabeans and prostate cancer
have suggested that this vegetable may help to reduce risk, but the
results are not conclusive (Hwang et al, 2009).
prevent cancer. Apart from a possible beneficial effect of
b-carotene combined with vitamin E and selenium in a poorly
nourished population in China, no benefits have been found at any
cancer site, and high-dose supplements of b-carotene may
EPIC van Duijnhoven et al (2009) 2819 0.88 (0.76–1.01) 0.92 (0.79–1.06) 0.86 (0.75–1.00)
NIH-AARP Park et al (2007) 2048 Men 1.06 (0.91–1.23) 0.82 (0.71–0.94) 0.91 (0.78–1.05)
924 Women 1.09 (0.88–1.36) 1.12 (0.90–1.38) 1.08 (0.86–1.35)
Pooling Project (colon only) Koushik et al (2007) 5838 0.93 (0.85–1.02) 0.94 (0.86–1.02) 0.91 (0.82–1.01)
Lung cancer
EPIC Büchner et al (2010) 1830 0.80 (0.66–0.96) 0.96 (0.79–1.17) —
NIH-AARP Wright et al (2008) 3834 Men 0.91 (0.82–1.02) 0.93 (0.83–1.03) 0.93 (0.83–1.04)
2201 Women 0.97 (0.84–1.11) 1.05 (0.92–1.21) 0.98 (0.85–1.13)
Pooling Project Smith-Warner et al (2003) 3206 0.77 (0.67–0.87) 0.88 (0.78–1.00) 0.79 (0.69–0.90)
Breast cancer
EPIC van Gils et al (2005) 3659 1.09 (0.94–1.25) 0.98 (0.84–1.14) —
Pooling Project Smith-Warner et al (2001) 7377 0.93 (0.86–1.00) 0.96 (0.89–1.04) 0.93 (0.86–1.00)
All cancers
EPIC Boffetta et al (2010) 30 604 0.94 (0.90–0.98) 0.93 (0.89–0.97) 0.89 (0.85–0.93)
Japan Public Health Center-Based
Prospective Study
Takachi et al (2008) 3230 1.02 (0.90–1.14) 0.94 (0.84–1.05) 0.96 (0.85–1.07)
NIH-AARP Diet and Health Study George et al (2009) 35 071 Men 0.98 (0.95–1.02) 0.94 (0.91–0.97) —
15 792 Women 0.99 (0.94–1.05) 1.04 (0.98–1.09) —
Nurses’ Health Study and Health
Professionals’ Follow-up Study
Hung et al (2004) 9261 1.01 (0.95–1.06) 0.99 (0.95–1.04) 1.00 (0.95–1.05)
Abbreviations: EPIC ¼ European Prospective Investigation into Cancer and Nutrition; NIH-AARP ¼ National Institutes of Health-American Association of Retired Persons Diet
and Health Study; Pooling Project ¼ Pooling Project of Prospective Studies of Diet and Cancer, a pooled analysis of primary data from 14 (colon cancer) and 8 (lung cancer,
breast cancer) prospective studies in North America and Europe, respectively; RR (95% CI) ¼ relative risk (95% confidence interval) of cancer for individuals in the highest
category of consumption compared with those in the lowest category.
Key, T. J. (2010). Fruit and vegetables and cancer risk. British Journal of Cancer, 104(1), 6–11

54. Dietary fat and colon cancer
#Global index is defined as the first of invasive breast cancer, any colorectal cancer, coronary heart disease, or death
due to other causes.
Figure 3. Kaplan-Meier Estimated Cumulative Hazards for Invasive Colorectal Cancer
(N=48 835)
No. of Events
Intervention
Comparison
No. at Risk
Intervention
Comparison
Cumulative
Hazard
0.005
0.010
0.015
0
0 1 2 4 5 6 7 8 9
3
26 23 23 27 16 28 18 9
22
27 32 43 44 33 33 22 11
32
19541 19402 19218 18784 18576 18290 15909 10507 5260
19004
29294 29070 28806 28259 27916 27622 23991 15806 7913
28554
Time, y
HR, 1.08 (95% CI, 0.90-1.29)
Weighted Log-Rank P=.29
Comparison
Intervention
HR indicates hazard ratio; CI, confidence interval.
Beresford, et al. (2006). Low-Fat Dietary Pattern and Risk of Colorectal Cancer. JAMA, 295(6), 643
• Women's Health Initiative
Dietary Modification Trial:
• 48,835 women were
randomly assigned to a
behavioral modification
program to decrease dietary
fat or a usual diet control
group
• Risk for colon cancer: HR
1.08 (95% CI, 0.90–1.29),
P=0.29
• No difference in colon cancer
risk at 8.1 years of follow up

55. Dietary fat and breast cancer
• Women’s Health Initiative
• no difference in breast
cancer incidence from
intervention and control
group
(F
fa
ti
m
ti
us
ag
m
ti
ho
pe
et
ph
so
m
ti
th
lin
pr
as
th
el
th
in
te
se
ca
Women taking postmenopausal hormone therapy or randomized in the hormone therapy trials were excluded from
the sample for hormone analysis.
†Change is calculated as the ratio of year 1 to baseline geometric means and is the ratio of changes in the intervention
group to the comparison group.
Figure 2. Kaplan-Meier Estimates of the Cumulative Hazard for Invasive Breast Cancer
0.01
0.02
0.03
0.04
0.05
0
0 1 2 4 5 6 7 8 9
3
Events
Intervention
Comparison
47 79 80 72 94 89 46 33
92
74 140 137 136 137 145 97 58
123
No. at Risk
Intervention
Comparison
19541 19328 19084 18520 18263 17900 15507 10245 5075
18798
29294 28908 28536 27806 27372 26977 23337 15373 7580
28195
Time, y
Cumulative
Hazard
Comparison
Intervention
HR, 0.91 (95% CI, 0.83-1.01)
Prentice, R. L., Caan, B., Chlebowski, R. T., Patterson, R., Kuller, L. H., Ockene, J. K., … Henderson, M. M. (2006). Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer. JAMA, 295(6), 629.

56. Dietary fat and prostate cancer
• diet high in animal fat may be an important factor in the development of
prostate cancer
• intake of large amounts of alpha-linoleic acid and low amounts of linoleic
acid appear to increase risk

57. Total fat?
Saturated, unsaturated, or trans fat?
Convincing evidence: excess calories
from any source → weight gain and
increase risk of multiple cancers
Cancer Epidemiol Biomarkers Prev. 2001;10(1):3.

58. • Red and processed meat is consistently associated with increased risk of
developing chronic diseases (1–3)
• including colorectal and prostate cancer
(1) PLoS One. 2011;6(6):e20456. Epub 2011 Jun 6. (2) Int J Cancer. 2016;138(10):2368. (3) J Intern Med. 2017;281(2):106. Epub 2016 Sep 6.

60. Group 1 human carcinogen
International Agency for Research on
Cancer

61. • Suggested mechanisms
• heme content in the meat
• animal fat
• carcinogens produced when the meat is cooked at high temperature

62. 2020 American Cancer Society guideline on diet
and physical activity for cancer prevention
ACS Diet & Physical Activity Guideline
TABLE 1. 2020 American Cancer Society Guideline on Diet and Physical Activity for Cancer Prevention
Recommendations for individuals
1.Achieve and maintain a healthy body weight throughout life.
• Keep body weight within the healthy range and avoid weight gain in adult life.
2. Be physically active.
• Adults should engage in 150-300 min of moderate-intensity physical activity per wk, or 75-150 min of vigorous-intensity physical activity, or an equivalent
combination; achieving or exceeding the upper limit of 300 min is optimal.
• Children and adolescents should engage in at least 1 hr of moderate- or vigorous-intensity activity each day.
• Limit sedentary behavior, such as sitting, lying down, and watching television, and other forms of screen-based entertainment.
3. Follow a healthy eating pattern at all ages.
• A healthy eating pattern includes:
◦ Foods that are high in nutrients in amounts that help achieve and maintain a healthy body weight;
◦ A variety of vegetables—dark green, red, and orange, fiber-rich legumes (beans and peas), and others;
◦ Fruits, especially whole fruits with a variety of colors; and
◦ Whole grains.
• A healthy eating pattern limits or does not include:
◦ Red and processed meats;
◦ Sugar-sweetened beverages; or
◦ Highly processed foods and refined grain products.
4. It is best not to drink alcohol.
CA Cancer J Clin. 2020;70(4):245. Epub 2020 Jun 9.

63. • Prospective studies on high intake of fruits and vegetables found
inconsistent results regarding cancer incidence (1–4)
• EPIC study: increased intake weekly associated with overall cancer risk
(hazard ratio [HR] 0.97, 95% CI 0.96-0.99) (5)
• High soy intake (20 mg/day of isoflavone) among Asian women vs low
intake (5 mg/day) associated with decreased risk for breast cancer (6)
(1) Cancer Epidemiol Biomarkers Prev. 2008;17(2):387, (2) Am J Epidemiol. 2008;167(1):59. (3) J Natl Cancer Inst. 2004;96(21):1577, (4) Am J Clin Nutr. 2009;89(1):347.
Epub 2008 Dec 3, (5) J Natl Cancer Inst. 2010;102(8):529. Epub 2010 Apr 6. (6) Br J Cancer. 2008;98(1):9. Epub 2008 Jan 8.

64. • inconsistent evidence
• relationship between dietary intake and ovarian cancer is uncertain
• low-fat dairy products may protect against breast cancer, especially in
premenopausal women (1)
• other studies did not confirm this
(1) J Natl Cancer Inst. 2002;94(17):1301.

65. Fiber
• intake of fiber associated with decrease in risk of colorectal cancer
• 9 percent lower risk of disease for every 10 g/day intake of foods
containing fiber (RR 0.91, 95% CI 0.88-0.94) (1)
(1) World Cancer Research Fund. Colorectal cancer: How diet, nutrition and physical activity affect colorectal (bowel) cancer risk. Available at: https://
www.wcrf.org/dietandcancer/colorectal-cancer (Accessed on April 28, 2020).

66. • Patients with diabetes have twofold or greater risk of liver, pancreatic,
endometrium, colon, breast, and bladder (1)
• hyperinsulinemia? (2)
• insulin and IGF can promote cell proliferation
• Inconsistent evidence
• no significant association between glycemic index or glycemic load
(calculated from food questionnaires) with 15,000 cases of cancer in
women or 33,000 cases of cancer in men (3)
(1) CA Cancer J Clin. 2010;60(4):207. Epub 2010 Jun 16. (2) Cancer Causes Control. 1995;6(2):164. (3) Am J Epidemiol. 2009;169(4):462. Epub 2008 Dec 18.

67. • no association between omega-3 fatty acids and cancer risk for 11
different types of cancer (1)
• decreased incidence in colon cancer associated with fish consumption (2)
(1) JAMA. 2006;295(4):403. (2) Am J Med. 2012;125(6):551. Epub 2012 Apr 17.

68. • Coffee associated with lower risk of certain cancers, including endometrial
and liver cancer
• For every 1 cup of coffee/day:
• 7 percent lower risk of endometrial cancer (RR 0.93, 95% CI
0.91-0.96)
• 14 percent lower risk of liver cancer (RR 0.86, 95% CI 0.81-0.90)
World Cancer Research Fund. Endometrial cancer: How diet, nutrition and physical activity affect endometrial (womb) cancer risk. Available at: https://www.wcrf.org/dietandcancer/
endometrial-cancer (Accessed on April 28, 2020).

69. Dietary patterns?
• Mediterranean diet (high intake of fruits, vegetables, nuts, legumes, whole
wheat bread, fish and olive oil) —4 to 12 percent lower risk of cancer (1,2)
• Vegetarian diet — 17 percent lower all-cause mortality compared to non-
vegetarian (3)
• Ultraprocessed food — ≥10 percent increases in risk of all-cancer and
breast cancer (4)
(1) Br J Cancer. 2008;99(1):191. (2) Br J Cancer. 2011 Apr;104(9):1493-9. Epub 2011 Apr 05. (3) Nutrients. 2014;6(6):2131. Epub 2014 May 27. (4) BMJ. 2018;360:k322. Epub 2018 Feb 14.

70. Multivitamins
• It has not been established that multivitamin and mineral supplements
provide added benefit to a balanced, healthful diet for most individuals (1,2)
• US Preventive Task Force recommends against (2, 3)
• supplementation with beta-carotene—increased risk for lung cancer
• supplementation with vitamin E—lack of benefit for reduction in cancer
risk
(1) Ann Intern Med. 2006;145(5):372. Epub 2006 Jul 31. (2) Ann Intern Med. 2013;159(12):824. (3) Ann Intern Med. 2014;160(8):558.

71. King RE, Angeles RR, Sacdalan DL. Herbal product and dietary supplement intake among patients at the Philippine General Hospital medical oncology clinic: a cross-sectional survey. Annals of
Oncology (2018) 29 (suppl_9): ix129-ix138. 10.1093/annonc/mdy444

72. King RE, Angeles RR, Sacdalan DL. Herbal product and dietary supplement intake among patients at the Philippine General Hospital medical oncology clinic: a cross-sectional survey. Annals of
Oncology (2018) 29 (suppl_9): ix129-ix138. 10.1093/annonc/mdy444

73. 5. Limit alcohol
• American Cancer Society (2020) recommends not drinking alcohol
• No more than 1 drink/day for women; 2 drinks/day for men (1)
• Moderate alcohol drinking can have beneficial effects on CV health in
adults, but increased cancer risk can offset the benefits (2,3)
• 3-6 drinks/week, small increased risk for breast cancer,
oropharyngeal and esophageal cancer (4)
(1) CA Cancer J Clin. 2020;70(4):245. Epub 2020 Jun 9. (2) Lancet. 2018;392(10152):1015. Epub 2018 Aug 23. (3) N Engl J Med. 1997;337(24):1705. (4) Ann Oncol. 2013;24(2):301. Epub
2012 Aug 21.

74. 6. Protect against sexually transmitted infections; vaccinate
girls and boys against human papillomavirus (HPV)
• 17 percent of all new cancers worldwide are due to infections (1)
• HPV vaccination
• Antiretroviral therapy, pre-exposure prophylaxis
• Treatment for hepatitis B and C
(1) American Cancer Society. Cancer Facts and Figures 2005. American Cancer Society, Atlanta, GA 2005.

75. Chemoprevention

76. Breast cancer
• Women at increased risk for breast cancer
• 35 years and older
• history of thoracic radiation prior to 30 years old
• history of lobular carcinoma in situ
• ≥1.7 percent risk for breast cancer
• atypical hyperplasia

77. • Post-menopausal women
• tamoxifen 20 mg/day — risk: endometrial cancer, thromboembolism
• raloxifene 60 mg/day
• aromatase inhibitors — risk: osteoporosis
• anastrozole 1 mg/day and exemestane 25 mg/day
• Premenopausal women
• tamoxifen 20 mg/day

78. PRIMARY CARE
Figure 1. Colon Carcinogenesis and the Effects of Chemopreventive Agents.
Colon cancers result from a series of pathologic changes that transform normal colonic epithelium into invasive carcinoma. Specific
genetic events, shown by vertical arrows, accompany this multistep process.8 The various chemopreventive agents exert their ef-
Normal
epithelium
Hyperproliferative
epithelium
Aberrant cryptic foci
Small
adenoma
Large
adenoma
Colon
carcinoma
Aspirin and
other NSAIDs
Folate
Calcium
Aspirin and
other NSAIDs
Estrogen
Aspirin and
other NSAIDs
APC
mutation
COX-2
overexpression
K-ras
mutation
p53
mutation
Loss of 18q
Jänne, P. A., & Mayer, R. J. (2000). Chemoprevention of Colorectal Cancer. New England Journal of Medicine, 342(26), 1960–1968.
Aspirin and colorectal carcinogenesis

79. Aspirin and colon cancer
The New England Journal of Medicine
Figure 2. Mechanisms of Action of Aspirin, Other Nonsteroidal Antiinflammatory Drugs, and Selective Cyclooxygenase-2 (COX-2)
Inhibitors.
The conversion of arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase (COX) family of enzymes, COX-1 and COX-
2.11 Aspirin and sulindac inhibit both COX-1 and COX-2, whereas celecoxib and rofecoxib inhibit only COX-2. These agents induce
+
Sphingomyelin
COX-1
COX-2
Angiogenesis
Ceramide
Nonselective inhibitors
(aspirin, sulindac)
Selective inhibitors
(celecoxib, rofecoxib)
PPARd
NF-kB
Non-COX
targets
COX-Dependent Mechanisms COX-Independent Mechanisms
Apoptosis
Phospholipids
Arachidonic acid
Prostaglandins
–
–
– –
–
–
+
+
–
Apoptosis
Apoptosis
Jänne, P. A., & Mayer, R. J. (2000). Chemoprevention of Colorectal Cancer. New England Journal of Medicine, 342(26), 1960–1968.

80. • Long-term daily low-dose aspirin for the primary prevention of colorectal
cancer and cardiovascular disease (1)
• aged 50 to 59 years
• 10-year risk of cardiovascular disease of 10 percent or higher
• do not have an increased bleeding risk
(1) UPSTF. Ann Intern Med. 2016 Jun;164(12):836-45. Epub 2016 Apr 12.

81. • Metformin associated with reduced incidence of several cancer types
• cancer incidence and mortality reduced by 30 percent (1)
• breast, colorectal, prostate, liver, and lung cancers
• pancreatic cancer in women (2)
(1) Cancer Prev Res (Phila). 2010;3(11):1451. Epub 2010 Oct 12. (2) Am J Gastroenterol. 2012;107(4):620. Epub 2012 Jan 31.

82. Metformin inhibits cell growth, colony formation
E
.
D
O
N
O
T
D
I
S
T
R
I
B
U
T
E
.
nhibits cell growth
e
e
y
n
g
n
l
s
c
e
h
,
y
l
f
-
n
,
h
l
s
n
s
Figure 1. Metformin inhibits breast cancer cell proliferation. Human breast
cancer cell lines (MCF7, MCF-7/713, BT474 and SKBR-3) were plated onto
96-well plates and incubated at 37°C with 5% CO2. After 24 hours, the
culture medium was replaced with control (0.1 ml fresh medium contain-
ing 0.5% FBS) or same medium containing a series doses of metformin for
another 72 hours incubation. The percentages of surviving cells from each
O
N
O
T
D
I
S
T
R
I
B
U
T
E
.
Metformin inhibits cell growth
Figure 2. Metformin inhibits colony formation of breast cancer cell lines. Human breast cancer cells (MCF7, MCF7/713, BT-474 and SKBR-3) were
in six-well plates (1,000 cells/well) in triplicates. After 24 hours, the culture medium was replaced with fresh medium containing 0.5% FBS as con
5.
Alimova, I. N., Liu, B., Fan, Z., Edgerton, S. M., Dillon, T., Lind, S. E., & Thor, A. D. (2009). Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro.
Cell Cycle, 8(6), 909–915.

83. D
I
S
T
R
I
B
U
T
E
.
Metformin inhibits cell growth

84. E
S
B
I
O
S
C
I
E
N
C
E
.
D
O
N
O
T
D
I
S
Figure 4. Effect of metformin on cell cycle progression in breast cancer cells. MCF-7, MCF-7/713, BT-474 and SKBR-3 cells were exposed to the indicated
concentrations of metformin for 24 hours. Both adherent and non-adherent cells were harvested. Cell cycle distributions were analyzed by flow cytometry
as described in the Materials and Methods.
Metformin causes cell-cycle growth arrest in the G1 phase
Alimova, I. N., Liu, B., Fan, Z., Edgerton, S. M., Dillon, T., Lind, S. E., & Thor, A. D. (2009). Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro.
Cell Cycle, 8(6), 909–915.

85. • Warfarin and statins — less convincing associations with cancer incidence

86. 1. Avoid tobacco
2. Be physically active
3. Maintain a healthy weight
4. Eat a diet rich in fruits, vegetables, and whole grains and low in saturated/trans
fat, red meat, and processed meat
5. Limit alcohol (zero is best)
6. Protect against sexually transmitted infections; vaccinate girls and boys
against human papillomavirus (HPV)
7. Give chemoprevention (breast, colon)
8. Screen for specific cancers
Colditz GA. Jan 2021. https://www.uptodate.com/contents/cancer-prevention?source=autocomplete&index=0~1&search=cancer%20prevention

87. Malignancy General recommendations
Breast cancer Starting 50 years old, mammogram annually
Colorectal cancer
Starting 50 years old:
colonoscopy every 10 years
FIT every 1-2 years (alternatively, use FOBT)
Cervical cancer
Starting 21 years old, pap smear every three years
Starting 30 years old:
pap smear every three years
pap smear + HPV co-testing every five years
Hepatocellular cancer
With cirrhosis or hepatitis B and C:
Liver ultrasound +/- AFP every 6 months
Lung cancer
55-74 years old, 30-pack years, quit within 15 years:
annual low dose CT scan