**3.1 HPV**

Of note, persistent HPV infections are now recognized as one of the causes of cancer. HPV is the cause of essentially all cervical cancers, as well as most cases of anal cancer. Genital HPV infection also causes some cancers of the vulva, vagina, and penis. In addition, oral HPV infection causes some cancers of the oropharynx and head and neck (Lowy and Munger 2010). HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV genes, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and retinoblastoma (RB) (inactivated by E7) (Dyson et al. 1989, Sherr and McCormick 2002, Storey et al. 1998, Werness, Levine and Howley 1990). As mentioned before, p53 is a tumor suppressor gene that arrests the cell cycle, prevents cell growth and stimulates apoptosis in the presence of DNA damage (Vogelstein et al. 2000). p53 also upregulates p21 which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F (Sherr and McCormick 2002). E6 has a close relationship with E6-associated protein (E6-AP) which is involved in the ubiquitin ligase pathway. E6- AP binds ubiquitin to p53, thereby flagging it for proteosomal degradation (Werness et al. 1990). In contrast, E7 competes for RB binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward (Dyson et al. 1989). Most HPV infections are cleared rapidly by the immune system and do not progress to cancer. Since the process of transforming normal cells into cancerous ones is slow, cancer occurs in people with persistent HPV infection.

#### **3.2 Alcohol**

72 Cancer Prevention – From Mechanisms to Translational Benefits

Head and neck

Head and neck

Lung

 Cervix Colon Esophagus Gall-bladder Kidney Liver Ovary Pancreas Prostate Stomach Uterus

 Colorectal Esophageal Liver Lung Melanoma Oral Pharyngeal Stomach

Of note, persistent HPV infections are now recognized as one of the causes of cancer. HPV is the cause of essentially all cervical cancers, as well as most cases of anal cancer. Genital HPV infection also causes some cancers of the vulva, vagina, and penis. In addition, oral HPV infection causes some cancers of the oropharynx and head and neck (Lowy and Munger 2010). HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV genes, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation. E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and retinoblastoma (RB) (inactivated by E7) (Dyson et al. 1989, Sherr and McCormick 2002, Storey et al. 1998, Werness, Levine and Howley 1990). As mentioned before, p53 is a tumor suppressor gene that arrests the cell cycle, prevents cell growth and stimulates apoptosis in the presence of DNA damage (Vogelstein et al. 2000). p53 also upregulates p21 which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F (Sherr and McCormick 2002). E6 has a close relationship

**Risk factor Cancer** 

**Tobacco**  Bladder

**Human papillomavirus**  Cervical

**Weight/ Diet**  Breast

**Alcohol**  Breast

Table 1. Preventable cancers and their risk factors.

**3.1 HPV** 

**Hepatitis**  Hepatocellular

Alcohol, a carcinogen, also causes a plethora of cancers (Wang et al. 2011, Chang, Straif and Guha 2011, Land et al. 2011, Pelucchi et al. 2008, Thomas 1995). Increased alcohol consumption has been linked to breast, liver, stomach, colorectal, melanoma, lung, and other cancers. Alcohol is thought to stimulate tumor growth by fuelling the production of growth factors that stimulate angiogenesis (Pelucchi et al. 2011). In addition, alcohol suppresses immune activity. Thus, alcohol should only be consumed in moderation.

#### **3.3 Smoking**

Cigarette smoking leads to lung cancer since smoking exposes the individual to multiple DNA-damaging carcinogens and mutagens that result in mutations in critical genes that control cellular growth (Gonzalez et al. 2011, Hymowitz 2011, Lam and Minna 2011, Pesch et al. 2011, Proctor et al. 2011, Shields 2011). Moreover, smokers are exposed to multiple tumor promoting substances and inflammatory agents that exacerbate the process. Effective tobacco control led by clean air legislation, taxation, and anti-tobacco advertising is gradually contributing to decreased lung cancer incidence ((CDC) 2011, Bajoga et al. 2011, Ballbe et al. 2011, Kasza et al. 2011, King et al. 2011a, King et al. 2011b, Mage et al. 2011, Walsh et al. 2011). Thorough understanding of the biochemical, genetic and behavioral mechanisms of smoking can help us identify people who have a particularly high susceptibility to tobacco promoted cancers. These individuals can then be targeted for novel prevention measures, such as a nicotine vaccination and chemoprevention. Other simple individual steps that can help against developing cancer include vaccination (discussed in detail in a subsequent section) and screening for cervical cancer and hepatitis B, avoidance of excessive sun exposure for skin cancer, and limiting alcohol consumption for head and neck cancer and liver cancer (Pelucchi et al. 2008, Thomas 1995, Herrero et al. 2011, Chang et al. 2011, Pelucchi et al. 2011, No et al. 2011). Education and public outreach are immensely critical in this field. To this end, as research resources are allocated on cancer prevention, simultaneously there is a need to support scientific research to better understand the specific causes and mechanisms of cancers. Effort to identify susceptible individuals and target them for preventive interventions is necessary.

#### **3.4 Diet**

A number of studies have examined the impact of diet on cancer risk. Both the quantity and quality of food plays a role in cancer, with the former thought to be more critical. Some foods do contain anticancer compounds. Phytonutrients, often found in pungent and bitter vegetables, include resveratrol in grapes and curcumin in turmeric (Azari et al. 2009, Feeney 2004, Greenlee, Hershman and Jacobson 2009, Holst and Williamson 2008, Kale, Gawande and

subtypes future studies should therefore attempt to characterize associations according to

A significant association between body mass index and higher cancer-induced mortality has been reported (**Table 1**) (Lampe 2007, Teucher, Rohrmann and Kaaks 2009, Boniol and Autier 2010, Gotay 2010, Khan, Afaq and Mukhtar 2010, Land et al. 2011, Lanzotti 2006, Li et al. 2011a). Specifically, a correlation between being overweight (excess body fat) and cancers of the esophagus, colon, liver, gall-bladder, pancreas, kidney, breast, uterus, cervix, ovary, prostate and stomach has been observed. But researchers have yet to fully decipher the link between being overweight and cancer. The mechanism likely depends on the type of malignancy. For instance, abdominal fat pressing on the stomach causes acid to splash up into the esophagus leading to tissue damage, which can ultimately result in esophageal cancer (Etemadi et al. 2011, Hall and Crowe 2011, Kong et al. 2011, Lagergren 2011, Li et al. 2011b, Olsen et al. 2011, Rutegard et al. 2011, Ryan et al. 2011). Estrogen, produced by fat cells, appears to play a role in endometrial cancer and breast cancer in postmenopausal women since it fuels cellular growth of estrogen receptor positive cancers (Bradlow et al. 2011, Colonna, Douglas Case and Lawrence 2011, Creighton et al. 2011, Perks and Holly 2011, Rondini et al. 2011, Sikalidis and Varamini 2011, Subbaramaiah et al. 2011, Willyard 2011, Yang et al. 2010). Androgen promotes some forms of prostate cancer as well (Aggarwal, Ryan and Chan 2011, Capitanio et al. 2011, Hoda et al. 2010, Ribeiro et al. 2010). Similarly, obesity promotes production of excess insulin which can promote growth of cancer. Interestingly, blockade of these receptors using antibodies and small molecular inhibitors have been shown to stop cancer cell proliferation. For example, Tamoxifen, an antagonist of the estrogen receptor, is currently used for the treatment of both early and advanced estrogen receptor positive breast cancer (University 2011, Amir et al. 2011, Braems et al. 2011, Cuzick et al. 2011, Doughty 2011, Fleeman et al. 2011, Gandhi and Verma 2011, Garrido et al. 2011, Goetz et al. 2011, Kilic et al. 2011, Kiyotani et al. 2011, Lin, Zhang and Manson 2011, Obiorah and Jordan 2011, Teunissen et al. 2011). Furthermore, it has also been approved by the FDA as a chemo preventative agent in women adjudged to be at high-risk of developing breast cancer (University 2011, Amir et al. 2011, Cuzick et al. 2011, Goetz et al. 2011). Similarly, people on metformin treatment to control their insulin level appear to have a lower risk of developing breast and pancreatic cancer (Papanas, Maltezos and Mikhailidis 2010, Rozengurt, Sinnett-Smith and Kisfalvi 2010, Suh and Kim 2011, Vigneri et al. 2009).

Regular physical activity cuts down on the risk of cancer as well. One proposed theory is that active people tend to digest their food faster, decreasing the chance of absorption of any carcinogenic products that happen to be going through the colon to be in contact with the mucosal lining (Azcárate-Peril, Sikes and Bruno-Bárcena 2011). In the same way, improved lung function limits exposure to airborne carcinogens, decreasing the risk of cancer. Interestingly, physically active individuals had lower estrogen levels compared to sedentary women, reducing their chance of developing the disease (Eliassen et al. 2010, Kossman et al. 2011, Lynch, Neilson and Friedenreich 2010, Phipps et al. 2011, Suzuki et al. 2011, Winzer et al. 2011). Thus, it is clear that simple healthy lifestyle choices can help reduce the chances of

A more drastic measure to prevent cancer is prophylactic surgery. It involves removal of as much of the at-risk tissue as possible in order to reduce the chance of developing cancer.

tumor characteristics.

developing cancer.

**3.5 Prophylactic surgery** 

Kotwal 2008, Kaur, Agarwal and Agarwal 2009, Lanzotti 2006, Mates et al. 2011, Mattoo et al. 2010, McGrath and Spigelman 2008, Neto 2007, Surh 2008, Wahlqvist and Lee 2007, Wenefrida et al. 2009). Other molecules, including sulforaphane and genistein, an isoflavone found in soybeans, are currently being tested as pharmaceutical agents in cancer prevention (Ali et al. 2005, Caetano et al. 2006, Takahashi et al. 2006, Shenouda et al. 2004). A healthy balanced diet with these nutrients can help prevent cancer. The barriers to the effectiveness of these phytonutrients lie in the genome and microbiomes. For instance, consumption of a known amount of the phytonutrient sulforaphane does not guarantee absorption of a predicted amount of anti-cancer molecule since differences in the glutathione S transferase M1 gene influences the metabolic rate of sulforaphane, a phytonutrient present in broccoli. The faster it is metabolized, the faster it is expelled from the body (Chung et al. 2000, Gasper et al. 2005, Gross-Steinmeyer et al. 2010, Joseph et al. 2004, Lampe 2007, Lampe 2009, McWalter et al. 2004, Riedl, Saxon and Diaz-Sanchez 2009, Ritz, Wan and Diaz-Sanchez 2007, Traka et al. 2008, Wan and Diaz-Sanchez 2007). Similarly, a number of the nutrients, e.g. isoflavones from soy, cannot be absorbed without the aid of microbes in the intestine (Di Cagno et al. 2010, Ding and Shah 2010, Rekha and Vijayalakshmi 2010, Szliszka et al. 2011, Szliszka and Krol 2011). Nonetheless, a healthy diet can reduce the chances of developing cancer.

Diet plays a vital role in the promotion of prostate cancer (Nelson, De Marzo and Isaacs 2003). Increased total fat intake, animal fat intake, and consumption of red meat have been associated with an increased risk of developing prostate cancer. In addition, the level of consumption of red meat correlates with the risk of prostate cancer (Giovannucci et al. 1993). Cooking meat at high temperatures or broiling on charcoal grills causes heterocyclic aromatic amine and polycyclic aromatic hydrocarbon carcinogens to form (Gross et al. 1993). Substantiating the claim, one such heterocyclic amine carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, causes prostate cancer when fed to rats (Shirai et al. 1997). On the other hand, antioxidant carotenoid lycopene found in tomatoes, isothiocyanate sulforaphane found in cruciferous vegetables, as well as other micronutrients may protect against prostate cancer by reducing oxidative genomic damage (Chan and Giovannucci 2001, Cohen, Kristal and Stanford 2000). Other antioxidants, such as vitamin E, isothiocyanate sulforaphane and selenium, may also reduce the risk of prostate cancer (Nelson et al. 2003, Hoque et al. 2001, Cohen et al. 2000, Heinonen et al. 1998). Factors involved in inflammation and angiogenesis, such as NFκB and vascular endothelial growth factor (VEGF) pathways, have been reported to be critical regulators in prostate carcinogenesis (Heymach et al. 2011).

The association between diet and breast cancer risk has been investigated extensively and has led to some recommendations for cancer prevention. Maintaining a healthy weight reduces the risk for breast cancer. Excess weight and weight gain in adult life are related to higher risk of postmenopausal breast cancer, and weight loss after menopause is associated with substantially reduced risk. Moderate levels of alcohol consumption increase the risk for breast cancer. Interestingly, this effect can be mitigated by adequate folate intake (Kim et al. 2011, Linos, Holmes and Willett 2007, Linos and Willett 2009, Linos and Willett 2007). Emerging research suggests that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention (Linos et al. 2010, Su et al. 2010, Holmes et al. 2009). Since breast cancer is a heterogeneous disease and dietary factors may differentially affect certain breast cancer

Kotwal 2008, Kaur, Agarwal and Agarwal 2009, Lanzotti 2006, Mates et al. 2011, Mattoo et al. 2010, McGrath and Spigelman 2008, Neto 2007, Surh 2008, Wahlqvist and Lee 2007, Wenefrida et al. 2009). Other molecules, including sulforaphane and genistein, an isoflavone found in soybeans, are currently being tested as pharmaceutical agents in cancer prevention (Ali et al. 2005, Caetano et al. 2006, Takahashi et al. 2006, Shenouda et al. 2004). A healthy balanced diet with these nutrients can help prevent cancer. The barriers to the effectiveness of these phytonutrients lie in the genome and microbiomes. For instance, consumption of a known amount of the phytonutrient sulforaphane does not guarantee absorption of a predicted amount of anti-cancer molecule since differences in the glutathione S transferase M1 gene influences the metabolic rate of sulforaphane, a phytonutrient present in broccoli. The faster it is metabolized, the faster it is expelled from the body (Chung et al. 2000, Gasper et al. 2005, Gross-Steinmeyer et al. 2010, Joseph et al. 2004, Lampe 2007, Lampe 2009, McWalter et al. 2004, Riedl, Saxon and Diaz-Sanchez 2009, Ritz, Wan and Diaz-Sanchez 2007, Traka et al. 2008, Wan and Diaz-Sanchez 2007). Similarly, a number of the nutrients, e.g. isoflavones from soy, cannot be absorbed without the aid of microbes in the intestine (Di Cagno et al. 2010, Ding and Shah 2010, Rekha and Vijayalakshmi 2010, Szliszka et al. 2011, Szliszka and Krol 2011). Nonetheless,

Diet plays a vital role in the promotion of prostate cancer (Nelson, De Marzo and Isaacs 2003). Increased total fat intake, animal fat intake, and consumption of red meat have been associated with an increased risk of developing prostate cancer. In addition, the level of consumption of red meat correlates with the risk of prostate cancer (Giovannucci et al. 1993). Cooking meat at high temperatures or broiling on charcoal grills causes heterocyclic aromatic amine and polycyclic aromatic hydrocarbon carcinogens to form (Gross et al. 1993). Substantiating the claim, one such heterocyclic amine carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, causes prostate cancer when fed to rats (Shirai et al. 1997). On the other hand, antioxidant carotenoid lycopene found in tomatoes, isothiocyanate sulforaphane found in cruciferous vegetables, as well as other micronutrients may protect against prostate cancer by reducing oxidative genomic damage (Chan and Giovannucci 2001, Cohen, Kristal and Stanford 2000). Other antioxidants, such as vitamin E, isothiocyanate sulforaphane and selenium, may also reduce the risk of prostate cancer (Nelson et al. 2003, Hoque et al. 2001, Cohen et al. 2000, Heinonen et al. 1998). Factors involved in inflammation and angiogenesis, such as NFκB and vascular endothelial growth factor (VEGF) pathways, have been reported to be critical regulators in prostate

The association between diet and breast cancer risk has been investigated extensively and has led to some recommendations for cancer prevention. Maintaining a healthy weight reduces the risk for breast cancer. Excess weight and weight gain in adult life are related to higher risk of postmenopausal breast cancer, and weight loss after menopause is associated with substantially reduced risk. Moderate levels of alcohol consumption increase the risk for breast cancer. Interestingly, this effect can be mitigated by adequate folate intake (Kim et al. 2011, Linos, Holmes and Willett 2007, Linos and Willett 2009, Linos and Willett 2007). Emerging research suggests that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention (Linos et al. 2010, Su et al. 2010, Holmes et al. 2009). Since breast cancer is a heterogeneous disease and dietary factors may differentially affect certain breast cancer

a healthy diet can reduce the chances of developing cancer.

carcinogenesis (Heymach et al. 2011).

subtypes future studies should therefore attempt to characterize associations according to tumor characteristics.

A significant association between body mass index and higher cancer-induced mortality has been reported (**Table 1**) (Lampe 2007, Teucher, Rohrmann and Kaaks 2009, Boniol and Autier 2010, Gotay 2010, Khan, Afaq and Mukhtar 2010, Land et al. 2011, Lanzotti 2006, Li et al. 2011a). Specifically, a correlation between being overweight (excess body fat) and cancers of the esophagus, colon, liver, gall-bladder, pancreas, kidney, breast, uterus, cervix, ovary, prostate and stomach has been observed. But researchers have yet to fully decipher the link between being overweight and cancer. The mechanism likely depends on the type of malignancy. For instance, abdominal fat pressing on the stomach causes acid to splash up into the esophagus leading to tissue damage, which can ultimately result in esophageal cancer (Etemadi et al. 2011, Hall and Crowe 2011, Kong et al. 2011, Lagergren 2011, Li et al. 2011b, Olsen et al. 2011, Rutegard et al. 2011, Ryan et al. 2011). Estrogen, produced by fat cells, appears to play a role in endometrial cancer and breast cancer in postmenopausal women since it fuels cellular growth of estrogen receptor positive cancers (Bradlow et al. 2011, Colonna, Douglas Case and Lawrence 2011, Creighton et al. 2011, Perks and Holly 2011, Rondini et al. 2011, Sikalidis and Varamini 2011, Subbaramaiah et al. 2011, Willyard 2011, Yang et al. 2010). Androgen promotes some forms of prostate cancer as well (Aggarwal, Ryan and Chan 2011, Capitanio et al. 2011, Hoda et al. 2010, Ribeiro et al. 2010). Similarly, obesity promotes production of excess insulin which can promote growth of cancer. Interestingly, blockade of these receptors using antibodies and small molecular inhibitors have been shown to stop cancer cell proliferation. For example, Tamoxifen, an antagonist of the estrogen receptor, is currently used for the treatment of both early and advanced estrogen receptor positive breast cancer (University 2011, Amir et al. 2011, Braems et al. 2011, Cuzick et al. 2011, Doughty 2011, Fleeman et al. 2011, Gandhi and Verma 2011, Garrido et al. 2011, Goetz et al. 2011, Kilic et al. 2011, Kiyotani et al. 2011, Lin, Zhang and Manson 2011, Obiorah and Jordan 2011, Teunissen et al. 2011). Furthermore, it has also been approved by the FDA as a chemo preventative agent in women adjudged to be at high-risk of developing breast cancer (University 2011, Amir et al. 2011, Cuzick et al. 2011, Goetz et al. 2011). Similarly, people on metformin treatment to control their insulin level appear to have a lower risk of developing breast and pancreatic cancer (Papanas, Maltezos and Mikhailidis 2010, Rozengurt, Sinnett-Smith and Kisfalvi 2010, Suh and Kim 2011, Vigneri et al. 2009).

Regular physical activity cuts down on the risk of cancer as well. One proposed theory is that active people tend to digest their food faster, decreasing the chance of absorption of any carcinogenic products that happen to be going through the colon to be in contact with the mucosal lining (Azcárate-Peril, Sikes and Bruno-Bárcena 2011). In the same way, improved lung function limits exposure to airborne carcinogens, decreasing the risk of cancer. Interestingly, physically active individuals had lower estrogen levels compared to sedentary women, reducing their chance of developing the disease (Eliassen et al. 2010, Kossman et al. 2011, Lynch, Neilson and Friedenreich 2010, Phipps et al. 2011, Suzuki et al. 2011, Winzer et al. 2011). Thus, it is clear that simple healthy lifestyle choices can help reduce the chances of developing cancer.

#### **3.5 Prophylactic surgery**

A more drastic measure to prevent cancer is prophylactic surgery. It involves removal of as much of the at-risk tissue as possible in order to reduce the chance of developing cancer.

**Cancer Drug Notes Reference** 

modulator

to prevent HPV infection

 Lodges in precancerous cells and upon exposure to light produces reactive species of

Kills surrounding cancer

Raloxifene Selective estrogen receptor modulator

oxygen

synthesis

oxygen

cells

Imiquimod Enhances immune response

cancer

Results in cell death

 Lodges in precancerous cells and upon exposure to light produces reactive species of

Kills surrounding cancer

Inhibits the conversion of

Promotes apoptosis

testosterone to dihydrotestosterone Prevents or delays the appearance of prostate

 Possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.

cells

(Vogel et al. 2006)

(Vogel et al. 2006)

(Einstein et al. 2009, Heard 2011, Saslow et al. 2007, Wheeler et al.

2011)

2006)

2010)

2010)

2003)

(Madan, Lear and Szeimies 2010)

(Madan et al.

(Madan et al.

(Thompson et al.

(Overholt, Panjehpour and Haydek 1999, Overholt et al. 2007, Panjehpour and Overholt

**Breast** Tamoxifen Selective estrogen receptor

**Cervical/vulvar/anal** HPV vaccine Promotes immune response

**Esophageal** Porfimer sodium

and

photodynamic therapy with omeprazole

**Skin** Fluorouracil Interferes with DNA

5-aminolevulinic

combination with Porfimer sodium

photodynamic therapy

**Prostate** Finasteride An inhibitor of 5α-reductase

Table 2. Chemo preventative drugs currently approved by the FDA.

acid in

and

Bilateral prophylactic mastectomy (removal of healthy breasts) and prophylactic salpingooophorectomy (removal of healthy fallopian tubes and ovaries) do not, however, offer a guarantee against developing cancer. Because not all at-risk tissue can be removed by these procedures, some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis even after prophylactic surgery.

Additionally, there are instances where despite strict lifestyles, cancer unfortunately will still develop. In these situations where prevention has failed, the next effective strategy is early detection of disease, which can improve the chance of beating cancer. Regular screening for cancer increases the chance of catching the disease early, while it is still treatable. Screening does not, however, change the risk of developing cancer. For example, breast cancer can be screened by mammography and clinical breast exams. Studies are currently under way to test the effectiveness of other breast cancer screening methods, such as magnetic resonance imaging (MRI), in women with BRCA1 or BRCA2 mutations. For ovarian cancer, surveillance methods include transvaginal ultrasound, blood tests for CA– 125 antigen, and clinical exams. Similarly, prostate cancer screening includes assaying prostate specific antigen (PSA) levels and digital rectal exam for lumps in the prostate. High PSA levels and lumps may be indicative of cancer but infection and inflammation may falsely elevate PSA levels as well. Routine colonoscopy to look for early signs of cancer is recommended at age 50 or earlier if there is a family history of colorectal cancer, a personal history of inflammatory bowel disease, or other risk factors. These strategies help in diagnosing cancer at its early stages.

The most effective steps to curb cancer are low-cost and low-tech. For example, giving up smoking and losing weight can drastically reduce the chances of developing cancer. Smoking has long been known to be a risk factor while obesity has more recently been recognized as one. Together they account for roughly half of all cancer cases (Ott et al. 2011, Brand et al. 2011, Land et al. 2011, Li et al. 2011a, Boniol and Autier 2010, Giovannucci et al. 2010, Gotay 2010, Khan et al. 2010, Teucher et al. 2009). Since these habits are easier said than done, policies that make unhealthy lifestyle choices difficult and expensive while making healthier ones easier and cheaper will be a step in the right direction. In addition, a number of clinical compounds have also been proposed to reduce the risk of carcinogenesis. These are discussed in detail below.
